The global dissemination of antimicrobial resistance (AMR) is a critical public health concern. The persistence of AMR in the environmental sector, exemplified by carbapenem-resistant Acinetobacter baumannii (CRAB), underscores the critical interconnectedness between human activity, environmental contamination, and the global spread of multidrug-resistant bacterial pathogens. In this study, A. baumannii strain EW779 was isolated from a water sample from a stream impacted by anthropogenic activities in São Paulo State, Brazil, exhibited an extensive drug resistance profile, and harbored chromosome-borne blaOXA-23 gene. Genomic analysis revealed that EW779 belongs to the hospital-associated high-risk ST79/ST233 subclone KL9-OCL10. This strain harbored a wide resistome associated with mobile genetic elements such as Tn2008, Tn7::In2-4, and Tn3. Virulence genes mainly related to biofilm formation, immune evasion, and cell invasion were found, evidencing its pathogenicity as putative hypervirulent. Comparative genomic analysis revealed that many AMR and virulence traits were shared among ST79/ST233 subclone KL9-OCL10 circulating in Brazil, indicating the occurrence of a successful and potentially epidemic subclone capable of spreading across different regions. The analysis of single nucleotide polymorphism differences among all ST79/ST233 subclone KL9-OCL10 showed a genetic similarity among strains from the same Brazilian state, indicating geographic separation. These findings highlight the environmental persistence and dissemination of a hospital-associated high-risk CRAB clone, emphasizing their epidemiological importance. Therefore, this study contributes to understanding the genomic dynamics of ST79/ST233 subclone KL9-OCL10 and reinforces the need for monitoring the spread of CRAB strains across clinical and environmental settings.

Acinetobacter baumannii has emerged as a critical nosocomial and environmental pathogen associated with high mortality rates and alarming levels of antibiotic resistance. The World Health Organization has classified A. baumannii as a top-priority pathogen due to its ability to rapidly acquire and disseminate resistance mechanisms. Prevalent in environmental reservoirs such as hospital effluents, agricultural runoff and pharmaceutical effluents, antibiotics' sub-minimum inhibitory concentrations (sub-MICs) drive resistance evolution in A. baumannii, posing challenges to treatment and public health strategies. This review examines the role of antibiotics' sub-MICs in driving resistance in A. baumannii across environmental and clinical contexts. Antibiotics' sub-MICs enhance bacterial resistance by inducing genetic and phenotypic adaptations. These include upregulated efflux pump activities, biofilm formation, horizontal gene transfers, and altered gene expression, enabling A. baumannii to persist in adverse conditions. Environmental reservoirs further exacerbate resistance, with antibiotics' sub-MICs of tigecycline and colistin promoting adaptive changes in bacterial physiology and virulence. Understanding these pathways in both environmental and clinical settings is essential to develop integrated strategies that mitigate resistance and improve therapeutic options against A. baumannii. This review emphasizes the need to address environmental reservoirs alongside clinical interventions to keep control on the resistance in a one health's approach.

Antibiotic-resistant bacteria (ARB) in hospital wastewater present significant but under-researched risks for wastewater treatment plant (WWTP) workers. This study evaluated annual infection risks (Py) from exposure to ESBL-producing Escherichia coli (ESBL E. coli) and the effectiveness of protective masks. Wastewater samples from 25 hospitals in Thailand revealed 88 % of untreated samples were positive for ESBL E. coli (6.25 × 102 to 1.83 × 107 CFU/100 mL, mean 2.22 × 106), while 40 % of treated samples tested positive (1.00 × 102 to 1.97 × 105 CFU/100 mL, mean 2.45 × 104). Using quantitative microbial risk assessment and data from 917 workers, risks were calculated under three scenarios: non-resistant, antibiotic-resistant, and highly virulent E. coli. Ingestion of aerosols and droplets posed a higher infection risk than hand-to-mouth contact, with Py often exceeding the U.S. EPA benchmark of 10-4 per person per year. Mask use, particularly surgical and FFP2 masks, significantly reduced risks, bringing treated wastewater exposure below the benchmark. However, highly virulent E. coli risks remained high across all mask types. These findings highlight the need for effective protective measures and disinfection strategies to safeguard WWTP workers and mitigate ARB dissemination, protecting public health and environmental safety.

Antimicrobial resistance (AMR) is a growing concern in veterinary and public health, with extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli playing a significant role. This study examined 1,000 healthy and sick dogs from a veterinary clinic in northern Germany and identified 85 ESBL-producing E. coli. Whole-genome sequencing of these isolates revealed seven phylogroups. A (38.8%) and B1 (32.9%) were the most common. Multilocus sequence typing identified 42 sequence types (STs), with the globally occurring lineages ST744 and ST10 being predominant. Single nucleotide polymorphism analysis showed the clonal circulation of ST744 among dogs in shared environments, such as households or breeders, whereas ST10 isolates displayed greater genetic diversity. ST131, a pathogenic international high-risk clonal lineage often associated with humans, was assigned to one isolate. Virulence-associated genes (VAGs) were abundant across the isolates, with siderophore systems, biofilm formation, and adherence traits being prominent. All isolates carried enterobactin genes with additional siderophore systems, such as yersiniabactin and aerobactin, present in 36 isolates. The highest number of VAGs (25) was observed in isolates belonging to the pathogenic lineages ST648 and ST405. Sixty-nine percent of the isolates were multidrug-resistant, carrying resistance genes for three or more antibiotic classes, with beta-lactam, aminoglycoside, and tetracycline resistance being the most frequent. This study highlights globally occurring E. coli lineages in companion animals and the role of close contact environments in their dissemination. Although dog-to-human transmission was not investigated in this study, these findings support the need for a One Health approach to address AMR, emphasizing the interconnected health of humans, animals, and the environment.IMPORTANCEThis study demonstrated the presence of globally significant Escherichia coli lineages in dogs and highlighted the impact of close-contact environments, such as households and breeders, on their spread. Many of the isolates exhibited genetic multidrug resistance and virulence features, posing challenges for effective treatment and control. These findings emphasize the interconnected nature of human, animal, and environmental health, underlining the need for a One Health approach to address antimicrobial resistance.

Klebsiella pneumoniae (K. pneumoniae) has become a serious global health concern due to its rising virulence and antibiotic resistance. As one of the leading members of ESKAPE pathogens, it plays a major role in a wide range of infections that cause pneumonia, urinary tract infections, and bacteremia, especially in immunocompromised and hospitalized patients. The recent increase in multidrug-resistant (MDR) and hypervirulent (hvKP) strains due to the production of extended-spectrum beta-lactamases (ESBLs) and carbapenemases, has greatly limited therapeutic options that highlights the need for novel approaches to combat the pathogen. This review outlines the virulence mechanisms, profiles of antibiotic resistance, and immune evasion strategies in K. pneumoniae. Also, it points out the role of capsular polysaccharides, lipopolysaccharides, and fimbriae in host colonization and immune evasion. Additionally, the review discusses the emerging therapeutic strategies of vaccine development, computational drug discovery, and the use of artificial intelligence (AI). The progress achieved in reverse vaccinology and structural biology enables the identification of new drug and vaccine targets, whereas AI and machine learning (ML) stand out as powerful candidates for high-throughput screening and drug design. However, challenges with antigenic variability, safety, and the need to collaborate globally still exist. This review focuses on the need for interdisciplinary approaches involving molecular biology and immunology with computational sciences to address K. pneumoniae infections and provide appropriate therapies in the era of antibiotic resistance.

The ubiquitous occurrence of antibiotics in the environment induces various stress responses of microbes and increases the risk of the emergence and spread of antimicrobial resistance (AMR). In this study, the transport and retention of Shewanella oneidensis cells in saturated porous media was investigated under different levels of ciprofloxacin (CIP) stress. Exposing to lethal CIP stress caused significant viability loss and stimulated cell transport due to increasing hydrophilicity and decreasing surface roughness. While exposure to sublethal CIP stress did not affect MR-1's viability, elongation of cells promoted their retention in sand columns via straining and orientation effects. The elongated cells likely adopted an end-on configuration to minimize repulsive interaction energy when approaching sand surfaces and deposited in a side-on position due to local surface roughness and charge heterogeneity of sands. The more diminished breakthrough of MR-1 cells in redox-active media was ascribed to their improving extracellular electron transfer and energy taxis activities under sublethal CIP stress. Moreover, the retention of elongated cells in porous media facilitated the de novo emergence of a resistant gyrase mutant, whose remobilization might exacerbate the AMR dissemination.

Antimicrobial resistance in bacteria is a global threat that can make antibacterial treatments ineffective. One well-known method of antibiotic resistance and a common defensive mechanism in many harmful bacteria is the synthesis of endogenous hydrogen sulfide (H2S) in bacteria. In this study, soil bacteria were screened using the lead acetate agar test and the triple sugar iron test to determine that they were non-endogenous H2S producers. This was further validated by full genome analysis of the identified organism against the gene sequences of H2S-producing genes. Antibacterial resistance of the bacteria was phenotypically analyzed using the Kirby-Bauer disk diffusion method. Then, the effect of exogenous H2S on the antibiotic-resistant bacteria was checked in sodium sulfide, leading to antibiotic re-sensitization.

Methicillin-resistant Staphylococcus aureus (MRSA) is a major global health threat due to its resistance to multiple antibiotics, making conventional treatments ineffective. The rise in antibiotic resistance highlights the urgent need for new therapies. Sortase A (SrtA), a key virulence factor in Staphylococcus aureus (S. aureus), facilitates bacterial adhesion and infection by anchoring surface proteins to host cells, making it a promising drug target. In this study, we investigated the potential of osmundacetone (OSC), a natural compound from Osmundae Rhizoma, as an SrtA inhibitor. Using fluorescence resonance energy transfer (FRET), OSC was found to inhibit SrtA with an IC50 of 1.29 μg/mL (7.24 μM). Further in vitro assays confirmed the effectiveness of OSC in inhibiting SrtA-mediated bacterial adhesion, invasion and biofilm formation. Fluorescence quenching and molecular docking pinpointed the binding site of OSC on SrtA. In vivo, OSC improved survival rates in MRSA-infected mice and Galleria mellonella (G. mellonella) while reducing bacterial loads in infected tissues. These results suggest OSC as a promising candidate for anti-MRSA therapies.

The widespread and indiscriminate use of biocides poses significant threats to global health, socioeconomic development, and environmental sustainability by accelerating antibiotic resistance. Bacterial resistance development is highly complex and influenced significantly by environmental factors. Increased biocide usage in households, agriculture, livestock farming, industrial settings, and hospitals produces persistent chemical residues that pollute soil and aquatic environments. Such contaminants contribute to the selection and proliferation of resistant bacteria and antimicrobial resistance genes (ARGs), facilitating their dissemination among humans, animals, and ecosystems. In this review, we conduct a critical assessment of four significant issues pertaining to this topic. Specifically, (i) the role of biocides in exerting selective pressure within the environmental resistome, thereby promoting the proliferation of resistant microbial populations and contributing to the global spread of antimicrobial resistance genes (ARGs); (ii) the role of biocides in triggering transient phenotypic adaptations in bacteria, including efflux pump overexpression, membrane alterations, and reduced porin expression, which often result in cross-resistance to multiple antibiotics; (iii) the capacity of biocides to disrupt bacteria and make the genetic content accessible, releasing DNA into the environment that remains intact under certain conditions, facilitating horizontal gene transfer and the spread of resistance determinants; (iv) the capacity of biocides to disrupt bacterial cells, releasing intact DNA into the environment and enhancing horizontal gene transfer of resistance determinants; and (iv) the selective interactions between biocides and bacterial biofilms in the environment, strengthening biofilm cohesion, inducing resistance mechanisms, and creating reservoirs for resistant microorganisms and ARG dissemination. Collectively, this review highlights the critical environmental and public health implications of biocide use, emphasizing an urgent need for strategic interventions to mitigate their role in antibiotic resistance proliferation.

Pork industry plays an important role in antibiotics consumption, which can lead to antimicrobial resistance (AMR) spread. Hence, monitoring and controlling AMR in swine production chains is essential to reduce the risks to public health. A systematic review protocol was developed to assess AMR in the pig production chain in Brazil, the fourth largest producer and exporter of pork in the world. More than 3000 strains obtained from swine chain had their antibiotic resistance characteristics assessed. Results showed a major attention to the research of swine AMR in Salmonella and Escherichia coli. Resistance against quinolones has been most investigated and high levels of resistance against tetracyclines were observed. Moreover, resistance profiles and determinants against colistin were frequently found. Meta-analyses were performed to estimate the frequency of microorganisms from the World Health Organization (WHO) global priority pathogens list of antibiotic-resistant bacteria. The results showed prevalences ≤ 0.11 of each priority group in Brazilian pork. As far as is known, this is the first research to provide a comprehensive synthesis of available data on AMR in this production chain. It may support the tackling of knowledge gaps and inspire the enhancement of policies to monitoring, controlling, and managing foodborne AMR.

Salmonella Dublin (S. Dublin) and Salmonella Typhimurium (S. Typhimurium) are commonly linked to bovine salmonellosis. S. Dublin is, however, considered a bovine-adapted serovar for primarily infecting and thriving in cattle. Using S. Typhimurium (a generalist serovar) as a benchmark, this study investigates genomic factors contributing to S. Dublin's adaptation to cattle hosts in the U.S. A total of 1337 S. Dublin and 787 S. Typhimurium whole-genome sequences from bovine sources were analyzed with CARD (version 4.0.0), ARG-NOTT (version 6), and AMRfinderPlus (version 4.0.3) for antimicrobial resistance (AMR) genes; VFDB and AMRfinderPlus for virulence genes; AMRFinderPlus for stress genes; and Plasmidfinder for plasmids. Existing clonal groups among isolates of the two serovars were also investigated using the Hierarchical Clustering of Core Genome Multi-Locus Sequence Typing (HierCC-cgMLST) model. The results revealed minimal genomic variation among S. Dublin isolates. Comparatively, the IncX1 plasmid was somewhat exclusively identified in S. Dublin isolates and each carried an average of four plasmids (p-value < 0.05). Furthermore, S. Dublin isolates exhibited a higher prevalence of AMR genes against key antimicrobials, including aminoglycosides, beta-lactams, tetracyclines, and sulfonamides, commonly used in U.S. cattle production. Additionally, Type VI secretion system genes tssJKLM and hcp2/tssD2, essential for colonization, were found exclusively in S. Dublin isolates with over 50% of these isolates possessing genes that confer resistance to heavy metal stressors, like mercury. These findings suggest that S. Dublin's adaptation to bovine hosts in the U.S. is supported by a conserved genetic makeup enriched with AMR genes, virulence factors, and stress-related genes, enabling it to colonize and persist in the bovine gut.

Small regulatory RNAs (sRNAs) in bacteria are crucial for controlling various cellular functions and provide immediate response to the environmental stresses. Antibiotic persistence is a phenomenon that a small subpopulation of bacteria survives under the exposure of a lethal concentration of antibiotics, potentially leading to the development of drug resistance in bacteria. Here, we reported a novel transposon-derived sRNA called stnpA, which can modulate fosfomycin persistence of the bacteria. The stnpA sRNA located in the transposon with its own promoter is highly conserved among the prevalent multidrug resistance (MDR) plasmids in various pathogenic bacteria and expressed in response to the fosfomycin stress. It can directly bind to the ABC transporter, YadG, whereas this protein-RNA interaction modulated the export of fosfomycin and led to the enhancement of bacterial persistence. According to our knowledge, stnpA is the first identified transposon-derived sRNA, which controlled antibiotic persistence of bacteria, and our work demonstrated that nonresistance genes on MDR plasmids such as plasmid-encoded sRNA can provide additional survival advantages to the bacterial host against the antibiotics. In addition, the stnpA sRNA can be potentially utilized as the druggable target for the development of novel therapeutic strategies to overcome bacterial persistence.

This study unveils a groundbreaking discovery in the realm of bacterial antibiotic persistence, highlighting the pivotal role of a newly identified small RNA (sRNA) called stnpA, which is a multidrug resistance plasmid-encoded transposon-derived sRNA that interacts directly with ABC transporter YadG to modulate the efflux of fosfomycin. Our findings elucidate a novel mechanism of small RNA-regulated fosfomycin persistence in bacteria that provides the potential pathway for the emergence of drug resistance in bacteria upon antibiotic treatment. Importantly, this study provides the first example of linking sRNA regulation to antibiotic persistence, presenting stnpA sRNA as a potential therapeutic target. This study underscores the critical role of noncoding RNAs in bacterial adaptation and offers valuable insights for developing new strategies to combat antibiotic persistence.

Over 80 MT of elemental sulfur, a byproduct of fossil fuel desulfurization, are generated annually. This has spurred the development of high sulfur content materials (HSMs) via inverse vulcanization as a productive pathway towards sulfur utilization. In this study, we evaluate the antimicrobial performance of SunBG90, an HSM made from brown grease and sulfur, as tiles or infused into fabric squares. The static antimicrobial activity of SunBG90 tiles was assessed, revealing excellent efficacy against Gram-positive bacteria, with reductions of 96.84% for Staphylococcus aureus and 91.52% for Listeria monocytogenes. The tiles also exhibited strong antifungal activity, reducing Candida auris by 96.20% and mold (fumigatus) by 83.77%. In contrast, efficacy against Gram-negative bacteria was more variable, with moderate reductions for Escherichia coli (61.10%) and Salmonella enteritidis (62.15%), lower activity against Campylobacter jejuni and Salmonella typhi, and no effect on Clostridium perfringens. Under dynamic conditions, SunBG90-infused fabrics achieved a near-complete inhibition of L. monocytogenes (99.91%) and high reduction of E. coli (98.49%), along with a 96.24% inhibition of Candida auris. These results highlight the potential and limitations of SunBG90 for antimicrobial applications, emphasizing the need for further optimization to achieve consistent broad-spectrum activity.

Listeria monocytogenes is an intracellular, Gram-positive, non-spore-forming, non-encapsulated, facultative anaerobic, rod-shaped, and psychrotrophic food-borne pathogen that causes the infection, listeriosis, thus it attracts great attention following listeriosis outbreaks, which are often associated with high mortality rates. The prevalence of listeriosis is quite low globally; however, the most recent and deadliest outbreak occurred in South Africa, during which 216 persons lost their lives. L. monocytogenes is endowed with the potential to multiply through a wide range of harsh environmental conditions, forming biofilms on varying surfaces in the food industry, as well as having persistent and antibiotic-resistant cells, which pose a major threat and burden to the ready-to-eat food industry. A more frustrating characteristic of this bacterium is its strain divergence, alongside an increased level of antibiotic resistance registered among the strains of L. monocytogenes recovered from food, humans, and environmental sources, especially to those antibiotics involved in the treatment of human listeriosis. Antibiotic resistance exerted by and among pathogenic food-borne microbes is an ongoing public health menace that continues to be an issue. Against this background, a thorough search into different databases using various search engines was performed, which led to the gathering of salient information that was organised, chronologically, based on Listeria monocytogenes and listeriosis. Altogether, the findings elaborated in this study present up-to date knowledge on different aspects of this pathogen which will improve our understanding of the mystery associated with it and the ways to prevent and control its dissemination through ready-to-eat foods. In addition, constant monitoring of the antibiotic resistance profiles of strains of L. monocytogenes from varying sources detected changes, giving an update on the trend in antibiotic resistance. Overall, monitoring of bacterial contamination serves as the key aspect in the control of the food safety output in the food industry.

The history of the conception of evolution of virulence is well known. However, in this period following the COVID-19 pandemic, it may be useful to recap such a current topic. In public debate, it has often been heard that COVID-19 was destined to evolve into a less virulent form because it would be in the virus's interest to coexist with the human population. This concept can be defined as the "Myth of the Good Pathogen" and originated from Smith's "law of declining virulence." The successes achieved thanks to vaccinations and antibiotics led the medical community, between the 1940s and the 1970s, to argue that the battle against infectious diseases had been won. However, the AIDS pandemic brought back down to earth the scientific community in their speculations about plagues. Since the 1970s, biologists have advanced the "virulence transmission trade-offs theory," a new model according to which intermediate virulence maximizes pathogenicity as a result of a trade-off between virulence and transmission. The introduction of trade-off models represented a crucial change that replaced the binary logic according to which natural selection shaped adaptations, whereas maladaptation escaped selection. This change was fundamental for the introduction of a new perspective in medicine, namely, Evolutionary Medicine, which might be an essential tool not only for understanding the dynamics of epidemics but also for preventing and curing infectious diseases.

The proliferation of multi-drug resistant (MDR) bacteria is driven by the global spread of epidemic lineages that accumulate antimicrobial resistance genes (ARGs). Acinetobacter baumannii, a leading cause of nosocomial infections, displays resistance to most frontline antimicrobials and represents a significant challenge to public health. In this study, we conduct a comprehensive genomic analysis of over 15,000 A. baumannii genomes to identify a predominant epidemic super-lineage (ESL) accounting for approximately 70% of global isolates. Through hierarchical classification of the ESL into distinct lineages, clusters, and clades, we identified a stepwise evolutionary trajectory responsible for the worldwide expansion and transmission of A. baumannii over the last eight decades. We observed the rise and global spread of a previously unrecognized Clade 2.5.6, which emerged in East Asia in 2006. The epidemic of the clade is linked to the ongoing acquisition of ARGs and virulence factors facilitated by genetic recombination. Our results highlight the necessity for One Health-oriented research and interventions to address the spread of this MDR pathogen.

Industrialization has driven lifestyle changes in eastern and western Chinese populations, yet we have a poor understanding of the dynamic changes in their gut microbiome and resistome under industrialization, which is essential for the scientific management of public health. Here, this study employed metagenomics to analyze the gut microbiota of 1,382 healthy individuals from China, including 415 individuals from the eastern region of advanced industrialization and 967 individuals from the western region of developing industrialization. Compared with western populations, eastern populations show a significant increase in interindividual dissimilarity of microbial species composition and metabolic pathways but a significant decrease in intraindividual species and functional diversity. Furthermore, our results found significantly less abundance and richness of antibiotic resistance genes (ARGs) in the gut microbiota of eastern populations, alongside a lower prevalence of unique core ARG subtypes. For the 12 core ARG types shared between eastern and western populations, the mean relative abundance of two types was notably higher in the eastern populations, while eight core ARG types had significantly higher mean relative abundance in the western populations. Based on the reconstruction of metagenomic assembled genomes, we found that Escherichia coli genomes from western populations carried more virulence factor genes (VFGs) and mobile genetic elements (MGEs) compared to those from eastern populations. This large-scale study for the first time revealed industrialization potentially led to unexpected alterations of the gut microbiome and resistome between eastern and western populations that provide a vital implication for Chinese public health and may aid in the development of region-specific strategies for managing pathogenic infections.

As China experiences rapid but uneven industrialization, understanding its effect on people's gut bacteria is critical for public health. This study reveals how industrialization may reshape the health risks related to gut bacteria and antibiotic resistance. This work provides crucial information to help create customized public health policies for different regions.

Chronic wound infections are caused by biofilm forming opportunistic pathogenic bacteria. The persistence of infection, co-infecting pathogens and prolonged use of antibiotics promote antibiotic resistance hampering healing process due to increased inflammation. Hence, we tested the broad range antibacterial activity of linalool, a bioactive monoterpene commonly present in many essential oils having anti-inflammatory and antimicrobial activities to target different opportunistic pathogens commonly found in the chronic wound. We included some of the common pathogens such as Acinetobacter baumannii, Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus, to study the broad range antimicrobial efficacy of linalool. The in vitro effect of linalool on biofilm was quantified in pre-treatment, post-treatment, repetitive treatment, and polymicrobial biofilm scenarios. Time-kill and XTT (2,3-bis [2-methyloxy-4-nitro-5-sulfophenyl]-2 H-tetrazolium-5-carboxanilide) assays were performed to confirm the efficacy of linalool against wound infections, and these results were further validated using simulated wound exudates medium (WEM) which mimics the wound environment. The mechanism of bactericidal action was determined using assays for membrane integrity and oxidative stress. The results indicated the broad range antimicrobial activity of linalool with minimum inhibitory concentration (MIC) ranging from 2.5 to 5 µL/mL against E. coli, A. baumannii, E. faecalis, S. aureus, and K. pneumoniae, while for P. aeruginosa the MIC was 20 µL/mL. Linalool was most effective against E. coli, E. faecalis, K. pneumoniae, A. baumannii, and S. aureus, and could inhibit the growth and biofilm by more than 90% and 80%, respectively, at 5 µL/mL. The XTT assay confirmed the MIC results, showing a significant reduction in the metabolic activity of the pathogens (p < 0.001). In the simulated WEM similar response of the bacteria to linalool treatment was observed. At 5 to 20 µL/mL concentrations, linalool significantly inhibited the polymicrobial biofilm consisting of P. aeruginosa, A. baumannii, and S. aureus in two species combinations. The mechanism of bactericidal action was associated with the increased reactive oxygen species production and disruption in the membrane integrity leading to release of cellular content. The anti-inflammatory activity of linalool, assessed using the albumin denaturation method showed significant activity at the tested concentrations. In conclusion, the findings suggest the therapeutic potential of linalool in treating biofilm associated chronic wound infections due to its versatile broad spectrum activity.

Recent research has uncovered new mechanisms that disrupt the balance between the host and microbes in the middle ear, potentially leading to dysbiosis and chronic suppurative otitis media (CSOM). Dysbiotic microbial communities, including core pathogens such as persister cells, are recognized for displaying cooperative virulence. These microbial communities not only evade the host's immune defenses but also promote inflammation that leads to tissue damage. This leads to uncontrolled disorder and pathogen proliferation, potentially causing hearing loss and systemic complications. In this discussion, we examine emerging paradigms in the study of CSOM that could provide insights into other polymicrobial inflammatory diseases. Additionally, we underscore critical knowledge gaps essential for developing a comprehensive understanding of how microbes interact with both the innate and adaptive immune systems to trigger and maintain CSOM.

Background: The fitness costs (FCs) of antimicrobial resistance (AMR) are crucial issues in antimicrobial resistance (AMR) onset, spread, and, consequently, public health. In Staphylococcus aureus, AMR can induce significant FCs due to slow growth, low competitiveness, and virulence. Here, we investigated the genomics and FCs emerging for progressively acquiring daptomycin (DAP) and glycopeptide (GLY) reduced susceptibility in MRSA. Methods: Genomics was carried out using Illumina-MiSeq Whole-genome sequencing and bioinformatics. The biological FCs of isogenic MRSA strain pairs progressively acquiring DAP and GLY-reduced susceptibility, under DAP/GLY mono or combined therapy, were performed by in-vitro independent and competitive mixed growth, phenotypic in-vitro virulence analysis, and in-vivo G. mellonella larvae killing. Results: Genomics evidenced four different extremely resistant high-risk clones, i.e., ST-5 N315 HA-MRSA, ST-398 LA-MRSA, ST-22 USA-100 HA-EMRSA-15, and ST-1 MW2 CA-MRSA. In-vitro fitness assays revealed slow growth, lower competitiveness, and reduced virulence, predominantly in Galleria mellonella killing ability, in DAP-S hGISA, DAP-R GSSA, DAP-R hGISA, and DAP-R GISA strains. Conclusions: The occurrence of glycopeptide and daptomycin reduced susceptibility conferred increasing FCs, paid as a gradual reduction in virulence, competitiveness, and slow growth performance.

Multidrug efflux pumps confer not only antibiotic resistance to bacteria but also cell proliferation. In gram-negative bacteria, the ATP-binding cassette (ABC)-family transporter MacB, the adaptor protein MacA, and the outer membrane protein TolC form the MacA6:MacB2:TolC3 assembly to extrude antibiotics and virulence factors. Here, using quantitative single-molecule single-cell imaging, we uncover that, in E. coli cells, there is a large excess of MacB (and TolC) driving the limiting adaptor protein MacA mostly into the MacAB-TolC assembly. Moreover, the excess MacB transporters can dynamically cluster around the assembly, and MacA can dynamically disassemble from the MacAB-TolC assembly, leading to an adaptor protein shuttling mechanism for efficient substrate sequestration from the periplasm toward efflux. We further show that both MacB clustering and MacAB-TolC assembly can be perturbed chemically or physically via microfluidics-based extrusion loading for compromised antibiotic tolerance. These insights may provide opportunities for countering the activities of multidrug efflux systems for antimicrobial treatments.

Mangrovibacter phragmitis is a Gram-negative bacterium typically found in plant roots that supports nitrogen fixation in nutrient-poor environments such as mangrove ecosystems. Although primarily found in environmental niches, an unusual case in Thailand of M. phragmitis strain PSU-3885-11 isolated from the sputum of a 29-year-old female patient with spinal tuberculosis. This isolate was initially misidentified as part of the Enterobacter cloacae complex (ECC) by MALDI-TOF. However, WGS subsequently confirmed its correct identity as M. phragmitis. The genome contains 4,651 coding sequences, along with 72 tRNA genes and 1 tmRNA. Moreover, comparative genomic analysis showed 99.32 % average nucleotide identity (ANI) similar to M. phragmitis MP23, and several antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) were identified in the PSU-3885-11 genome which may contribute to its ability to survive in diverse environments, including human hosts. The PSU-3885-11 displayed resistance to beta-lactam antibiotics such as ampicillin and cefotaxime, while remaining sensitive to a wide range of other antibiotics. Key virulence genes including ompA, hcp/tssD, and rpoS, were identified which may play a role in its persistence in human hosts as an opportunistic pathogen. The presence of ribosomally synthesized and post-translationally modified peptides (RiPPs) and bacteriocins indicates the antimicrobial properties that may provide a competitive advantage in both environmental and clinical settings of this strain. Therefore, this study provides valuable insights into the genomic features, antibiotic resistance, and potential pathogenicity of M. phragmitis PSU-3885-11. The findings also emphasize the importance of continued surveillance and genomic analysis of environmental bacteria that may emerge as opportunistic pathogens in human infections.

F plasmids are abundant in E. coli, carrying a variety of genetic cargo involved in fitness, pathogenicity, and antimicrobial resistance. ColV and pUTI89-like plasmids have drawn attention for their potential roles in various forms of extra-intestinal pathogenicity. However, the rates of their carriage and the overall diversity of F plasmids in E. coli bloodstream infections (BSI E. coli) remain unknown.

We performed a t-SNE-based cluster analysis of predicted F plasmids from a collection of 4711 BSI E. coli draft genomes to describe their diversity and abundance. We also screened them for markers of ColV and pUTI89-like plasmids, F plasmid replicon sequence types (RST) and E. coli sequence types (ST) to understand how genetic features were related to plasmid clusters.

Predicted F plasmids in BSI E. coli draft genomes were embedded within five major clusters based on a model of complete F plasmid sequences. Nearly half of the clustered sequences belonged to two major clusters, which were associated with ColV and pUTI89-like marker genes, respectively. Genomes from the ColV cluster featured F2:A-:B1 and F24:A-B1 RSTs in association with ST95, ST58 and ST88, whilst the pUTI89-like cluster was mostly F29:A-:B10 linked to ST73, ST69, ST95 and ST131. Plasmids associated with different lineages of ST131 formed additional major clusters, whilst F51:A-:B10 plasmids in ST73 were also common.

ColV and pUTI89-like plasmid markers are predominant in BSI E. coli that carry F plasmids. These markers are associated with distinct clusters of plasmids across diverse sequence types of E. coli. We hypothesise that their abundance in BSI E. coli is partially driven by carriage of backbone genes previously shown to contribute to virulence in models of bloodstream infection. Their carriage by pandemic E. coli STs suggests clonal expansion also plays a role in their success in BSI. Ecological pathways via which these plasmids evolve, and spread are likely to be distinct as other studies show ColV is strongly associated with poultry and food animal production, whereas pUTI89-like plasmids appear to be mostly human-restricted.

Pseudomonas aeruginosa (PA), as a common pathogen of nosocomial infections, has been experiencing an increasing rate of drug resistance with the widespread use and abuse of antimicrobial drugs. High-drug-resistance and high-virulence phenotypes are two distinctive features of the strong pathogenicity of multi-drug-resistant PA. Exploring the characterization of virulence factor expression and its relationship with the multi-drug resistance phenotype is essential to reduce the further development of resistance as well as a high standard of infection prevention and control. A total of 50 PA isolated from clinical practice were collected. The Kirby-Bauer test was used for drug-sensitive screening, and the results showed that 16 strains were resistant and 16 strains were sensitive. The drug resistance rate of multi-drug-resistant PA against cefepime, cefazolin, ampicillin, and imipenem was up to 100%. The multi-drug-resistant groups were superior in producing pyocyanin and forming biofilm to the sensitive groups. The distribution of isolates with different swarming motility capacities and elastase levels did not show pronounced differences among the multi-drug-resistant and sensitive groups. In addition, biofilm formation was moderately associated with imipenem resistance. Among the strains with strong virulence factor expression, the gene bands showed little difference, suggesting that the gene is highly homologous. The virulence factor matrix analysis showed that there were different degrees of correlation among the 4 virulence factors. The correlation between multidrug-resistant PA and virulence factor expression is complex. PA, which were good at producing pyocyain and forming biofilm, were highly resistant to cephalosporins, beta-lactams and carbepenems; hence, such drugs are not proper for anti-infective treatment in clinics.

Controlling microbial pollutants is a significant public health concern as they cause several chronic microbial infections and illnesses. In recent years, essential oils (EOs) have become intriguing alternatives for synthetic antimicrobials due to their biodegradability, natural source extraction, and strong antibacterial properties. The bactericidal properties of alginate containing lemon essential oil were examined in this investigation. Following the screening of the MDR strains, the morphological properties of the produced nanoparticles were examined using SEM, DLS, and FTIR. Additionally, the durability, effectiveness, and drug dispersion of encapsulation were assessed. Bacterial virulence factor gene amounts were measured using Q-real-time PCR. Concurrently, the cytotoxic effect of the nanomaterials was evaluated using MTT techniques. Nanoparticles of lemon essential oil encapsulated in alginate, measuring 500 ± 19.32 nm in size, with entrapment efficiency of 77.73 ± 1.78% and were stable for 60 days at 4 °C. Alginate encapsulated with lemon essential oil nanoparticles (ALN) exhibited potent antibacterial qualities, according to the biological investigation. Their ability to decrease the transcription of bacterial virulence genes at least statistically significantly (P ≤ 0.05) served as evidence for this. Between 1.56 and 100 µg/mL (P ≤ 0.01), ALN exhibited lower cytotoxicity against CCD841CoN than free lemon essential oil. The findings show that ALN nanoparticles have the potential to be a breakthrough in the fight against highly resistant illnesses. ALN nanoparticles' potent antibacterial efficacy against MDR strains of Acinetobacter baumannii may inspire new directions in antibacterial research.

Due to their considerable chemical diversity, metal compounds are attracting increasing and renewed attention from the scientific and medical communities as potential antimicrobial agents to combat the growing problem of antibiotic resistance. The development of metal compounds as antimicrobial agents typically follows classical drug discovery procedures and suffers from the same problems; indeed, these procedures can be very expensive and time-consuming, and carry an intrinsically high risk of failure. Here, we show how some established drug discovery approaches can be conveniently and successfully applied to antimicrobial metal compounds to provide some shortcuts for faster clinical translation of new treatments. Specifically, we refer to (i) drug repurposing, (ii) drug combination and (iii) drug targeting by bioconjugation; some relevant examples will be illustrated.

Several antibiotic candidates are in development against Gram-positive bacterial pathogens, but their long-term utility is unclear. To investigate this issue, we studied the laboratory evolution of resistance to antibiotics that have not yet reached the market. We found that, with the exception of compound SCH79797, antibiotic resistance generally readily evolves in Staphylococcus aureus. Cross-resistance was detected between such candidates and antibiotics currently in clinical use, including vancomycin, daptomycin, and the promising antibiotic candidate teixobactin. These patterns were driven by overlapping molecular mechanisms through mutations in regulatory systems. In particular, teixobactin-resistant bacteria displayed clinically relevant multidrug resistance and retained their virulence in an invertebrate infection model, raising concerns. More generally, we demonstrate that putative resistance mutations against candidate antibiotics are already present in natural bacterial populations. Therefore, antibiotic resistance in nature may evolve readily from the selection of preexisting genetic variants. Our work highlights the importance of predicting future evolution of resistance to antibiotic candidates at an early stage of drug development.

This study aims to characterize antibiotic resistance (AR) and virulence markers in Salmonella spp. isolated from Romanian outpatients' stool samples.

In 2019, community-acquired Salmonella strains were collected and identified using MALDI-TOF mass spectrometry, antibiotic susceptibility profiles have been determined with the MicroScan system, and soluble virulence factors were evaluated using specific culture media, while biofilm formation was quantified in 96-well plates. Molecular analysis targeted resistance genes for β-lactams (e.g., blaTEM and blaSHV); tetracyclines (e.g., tet(A)); sulphonamides; and quinolones, as well as virulence genes (e.g., invA, spvC, pldA, and held). Whole-genome sequencing (WGS) was performed on 19 selected isolates. A silver nanoparticles (AgNPsol) alternative to conventional antibiotics was tested for effectiveness against multidrug-resistant (MDR) isolates.

From the total of 309 Salmonella isolates (65.05% from children under 4 years of age) belonging to four subtypes and four serovars, 27.86% showed resistance to at least one antibiotic, most frequently to tetracycline, ampicillin, and piperacillin. The strains frequently expressed haemolysin (67%), aesculinase (65%), and gelatinase (62%). Resistance to trimethoprim-sulfamethoxazole was encoded by the sul1 gene in 44.83% of the strains and to tetracyclines by the tet(A) gene (59.52%). The ESBL genes blaTEM, blaSHV, and blaCTX-M were detected by PCR in 16.18%, 2.91%, and 0.65% of the strains, respectively. Additionally, 98.63% of the strains carried the invA marker, with notable positive associations between blaSHV, qnrB, and sul1 with spvC.

The present findings revealed significant patterns in Salmonella isolates, subtypes, serovars, AR, and virulence, emphasising the need for continuous surveillance of Salmonella infections. Additionally, the potential of AgNPs as an alternative treatment option was demonstrated, particularly for paediatric S. enterica infections.

The increase in antibiotic resistance, together with the absence of novel antibiotics, makes mandatory the introduction of novel strategies to optimize the use of existing antibiotics. Among these strategies, the use of molecules that increase their activity looks promising.

Different categories of adjuvants have been reviewed. Anti-resistance adjuvants increase the activity of antibiotics by inhibiting antibiotic resistance determinants. Anti-virulence approaches focus on the infection process itself; reducing virulence in combination with an antibiotic can improve therapeutic efficacy. Combination of phages with antibiotics can also be useful, since they present different mechanisms of action and targets. Finally, combining antibiotics with adjuvants in the same molecule may serve to improve antibiotics' efficacy and to overcome potential problems of differential pharmacokinetics/pharmacodynamics.

The successful combination of inhibitors of β-lactamases with β-lactams has shown that adjuvants can improve the efficacy of current antibiotics. In this sense, novel anti-resistance adjuvants able to inhibit efflux pumps are still needed, as well as anti-virulence compounds that improve the efficacy of antibiotics by interfering with the infection process. Although adjuvants may present different pharmacodynamics/pharmacokinetics than antibiotics, conjugates containing both compounds can solve this problem. Finally, already approved drugs can be a promising source of antibiotic adjuvants.

Escherichia coli (E. coli), a normal intestinal microbiota is one of the most common pathogen known for infecting urinary tract, wound, lungs, bone marrow, blood system and brain. Irrational and overuse of commercially available antibiotics is the most imperative reason behind the emergence of the life threatening infections caused due to antibiotic resistant pathogens. The World Health Organization (WHO) identified antimicrobial resistance (AMR) as one of the 10 biggest public health threats of our time. This harmless commensal can acquire a range of mobile genetic elements harbouring genes coding for virulence factors becoming highly versatile human pathogens causing severe intestinal and extra intestinal diseases. Although, E. coli has been the most widely studied micro-organism, it never ceases to astound us with its ability to open up new research avenues and reveal cutting-edge survival mechanisms in diverse environments that impact human and surrounding environment. This review aims to summarize and highlight persistent research gaps in the field, including: (i) the transfer of resistant genes among bacterial species in diverse environments, such as those associated with humans and animals; (ii) the development of resistance mechanisms against various classes of antibiotics, including quinolones, tetracyclines, etc., in addition to β-lactams; and (iii) the relationship between resistance and virulence factors for understanding how virulence factors and resistance interact to gain a better grasp of how resistance mechanisms impact an organism's capacity to spread illness and interact with the host's defences. Moreover, this review aims to offer a thorough overview, exploring the history and factors contributing to antimicrobial resistance (AMR), the different reported pathotypes, and their links to virulence in both humans and animals. It will also examine their prevalence in various contexts, including food, environmental, and clinical settings. The objective is to deliver a more informative and current analysis, highlighting the evolution from microbiota (historical context) to sophisticated diseases caused by highly successful pathogens. Developing more potent tactics to counteract antibiotic resistance in E. coli requires filling in these gaps. By bridging these gaps, we can strengthen our capacity to manage and prevent resistance, which will eventually enhance public health and patient outcomes.

The antibiotic resistance genes (ARGs) have become a serious issue facing public health. In this study, light-burned magnesite with a high specific surface area at 650 °C (MS650) was used for aerobic composting, evaluating its effect on the resistome during pig manure composting. Different concentrations of MS650 reduced the abundance of the resistome, including seven high-risk ARGs, class two metal and biocide resistance genes (MBRGs), and human pathogenic bacteria (HPBs). The addition of 2.5 % MS650 (L1) in the composting had the best reduction effect on ARGs, MBRGs and HPBs. ARG and microbial community assembly are deterministic processes. Proteobacteria and Actinobacteria was the main factor associated with the decrease in ARGs, followed by virulence factor genes (VFGs, 44.2 %). The reduction in MBRGs by MS650 mainly suppressed HGT by reducing the Isfinder abundance. To summarize, MS650 is an effective method to improve emission reduction of ARGs and MBRGs. This study provided a theoretical basis for improving the engineering application potential of MS650.

The rise of antimicrobial resistance (AMR) remains a pressing global health challenge. Infections that were once easily treatable with first-line antimicrobials are becoming increasingly difficult to manage. This shift directly threatens the wellness of humans, animals, plants, and the environment. While the AMR crisis can be attributed to a myriad of factors, including lack of infection prevention and control measures, over-prescription of antimicrobials, patient non-compliance, and the misuse of antimicrobials, one aspect that has garnered less attention is the role of storage conditions of these medicines. The way medications, particularly antimicrobials, are transported and stored until the point of use can influence their efficacy and, subsequently, may impact the development of resistant microbial strains. This review delves deeper into the often-overlooked domain of climate change (CC) and antimicrobial storage practices and the potential effects. Inappropriate storage conditions, such as exposure to extreme temperatures, humidity or light, can degrade the potency of antimicrobials. When these compromised medicines are administered to patients or animals alike, they may not effectively eradicate the targeted pathogens, leading to partial survival of the pathogens. These surviving pathogens, having been exposed to sub-lethal doses, are more likely to evolve and develop resistance mechanisms. The review discusses the mechanism underlying this and underscores the implications of antimicrobial storage practices in relation to two of the most pressing global health challenges: AMR and CC. The review also presents specific case studies and highlights the importance of monitoring storage practices and supply chain surveillance. Furthermore, the importance of deploying genomic tools to understand the potential impact of storage conditions on the development of AMR is discussed, and antimicrobial storage highlighted as a crucial part of comprehensive strategies in the fight against AMR.

The escalating antimicrobial resistance (AMR) in highly virulent Vibrio vulnificus poses a significant public health concern in Asia. Profiling the antibiogram of this pathogen is crucial for revealing its complex AMR patterns and guiding the selection of appropriate medications. Although previous studies have provided valuable insights regarding V. vulnificus AMR, they are constrained by limited sample diversity, inconsistent methodologies, and insufficient regional data. Moreover, no systematic attempt has been made to synthesize V. vulnificus AMR data across various sources and regions in Asia. A systematic review and meta-analysis are thus conducted in this study to assess the current AMR status of V. vulnificus isolated from clinical, environmental, and seafood samples. By synthesizing data from 32 articles across 13 Asian countries, a broader antibiogram has been provided, covering 13 major antimicrobial groups against V. vulnificus. Subgroup and regression analyses were also performed using study-level and country-specific covariates to explore the associated risk factors. The findings revealed low AMR rates for tetracyclines (4.89 %), quinolones (1.85 %), nitrofurans (0.86 %), and phenicols (0.61 %), highlighting their potential as primary treatment options. Conversely, high AMR rates were detected for lincosamides (80.32 %), polypeptides (64.42 %), and glycopeptides (56.14 %), necessitating careful consideration for their clinical use. For study-level covariates, subgroup and meta-regression analyses revealed that variations in the type of antimicrobial (R 2  = 26.5 %, p < 0.0001), country (R 2  = 18.33 %, p < 0.0001), and pathogen source (R 2  = 10.46 %, p = 0.0007) significantly contributed to between-study heterogeneity in the detected AMR rates across studies. Moreover, the analyses of country-specific covariates indicated that antimicrobial consumption (AMC) in healthcare systems (R 2  = 29.3, p = 0.06) and the country's gross domestic product (GDP) (R 2  = 28.59, p = 0.06) affected the variations in AMR rates across countries to some extent. Consideration of study-level and country-specific covariates is thus recommended for future research to effectively mitigate the threat of V. vulnificus AMR across Asia and reduce its pervasive impact on public health.

Agricultural soils are important source and sink of antibiotic resistance genes (ARGs). However, little is known about the fate of ARGs in dryland soils, while its human exposure risks were seriously overlooked. Taking the northern Ningxia Plain as a case, this study explored the occurrence of ARGs and its relationship with mobile genetic elements (MGEs), pathogens, and environmental factors. Furthermore, the concentrations of airborne ARGs by soil wind erosion and the human exposure doses of soil ARGs were evaluated. The results showed the abundances of different regions ranged from 4.0 × 105 to 1.6 × 106 copies/g. Soil ARGs are driven by MGEs, but multiply impacted by soil properties, nutrition, and bacterial community. Vibrio metschnikovii, Acinetobacter schindleri, and Serratia marcescens are potential pathogenic hosts for ARGs. Further exploration revealed the concentration of ARGs loaded in dust by soil wind erosion reached more than 105 copies/m3, which were even higher than those found in sewage treatment plants and hospitals. Skin contact is the primary route of ARGs exposure, with a maximum dose of 24071.33 copies/kg/d, which is largely attributed to ARGs loaded in dust. This study bridged the gap on ARGs in dryland soils, and provided reference for human exposure risk assessment of soil ARGs.

The impact of antimicrobial resistance (AMR) on death at the patient level is challenging to estimate. We aimed to characterize AMR-attributable deaths in a large UK teaching hospital.

This retrospective study investigated all deceased patients in 2022. Records of participants were independently reviewed by two investigators for cases of AMR-attributable deaths using a newly proposed patient-level definition.

In total, 758 patients met inclusion criteria. Infection was the underlying cause of death for 11.7% (89/758) and was implicated in the pathway that led to death in 41.1% (357/758) of participants. In total, 4.2% (32/758) of all deaths were AMR-attributable. Median time from index sample collection to death was 4.5 days (IQR 2-10.5 days). The majority of AMR-attributable deaths (56.3%, 18/32) were associated with intrinsic resistance mechanisms, primarily by Enterococcus faecium (20.7%), Enterobacterales carrying repressed chromosomal ampicillinase Cs (AmpCs) (14.7%) and Pseudomonas aeruginosa (11.8%), whereas a minority (43.7%, 14/32) had acquired resistance mechanisms, primarily derepressed chromosomal AmpCs (11.8%) and ESBLs (8.8%). The median time to effective treatment was 32 h 15 min (no difference between subgroups). Only 62.5% (20/32) of AMR-attributable deaths had infection recorded on the death certificate. AMR was not recorded as a cause of death in any of the patients.

Infection and AMR were important causes of death in our cohort, yet they were significantly underreported during death certification. In a low-incidence setting for AMR, pathogen-antimicrobial mismatch due to intrinsic resistance was an equally important contributor to AMR-attributable mortality as acquired resistance mechanisms.

β-N-acetylglucosaminidase (NagZ), a cytosolic glucosaminidase, plays a pivotal role in peptidoglycan recycling. Previous research demonstrated that NagZ knockout significantly eradicated AmpC-dependent β-lactam resistance in Enterobacter cloacae. However, NagZ's role in the virulence of E. cloacae remains unclear. Our study, incorporating data on mouse and Galleria mellonella larval mortality rates, inflammation markers, and histopathological examinations, revealed a substantial reduction in the virulence of E. cloacae following NagZ knockout. Transcriptome sequencing uncovered differential gene expression between NagZ knockout and wild-type strains, particularly in nucleotide metabolism pathways. Further investigation demonstrated that NagZ deletion led to a significant increase in cyclic diguanosine monophosphate (c-di-GMP) levels. Additionally, transcriptome sequencing and RT-qPCR confirmed significant differences in the expression of ECL_03795, a gene with an unknown function but speculated to be involved in c-di-GMP metabolism due to its EAL domain known for phosphodiesterase activity. Interestingly, in ECL_03795 knockout strains, a notable reduction in the virulence was observed, and virulence was rescued upon complementation with ECL_03795. Consequently, our study suggests that NagZ's function on virulence is partially mediated through the ECL_03795→c-di-GMP pathway, providing insight into the development of novel therapies and strongly supporting the interest in creating highly efficient NagZ inhibitors.

Previous studies on disease in coral reef organisms have neglected the natural distribution of potential pathogens and the genetic factors that underlie disease incidence. This study explores the intricate associations between hosts, microbial communities, putative pathogens, antibiotic resistance genes (ARGs) and virulence factors (VFs) across diverse coral reef biotopes. We observed a substantial compositional overlap of putative bacterial pathogens, VFs and ARGs across biotopes, consistent with the 'everything is everywhere, but the environment selects' hypothesis. However, flatworms and soft corals deviated from this pattern, harbouring the least diverse microbial communities and the lowest diversity of putative pathogens and ARGs. Notably, our study revealed a significant congruence between the distribution of putative pathogens, ARGs and microbial assemblages across different biotopes, suggesting an association between pathogen and ARG occurrence. This study sheds light on the existence of this latent pathobiome, the disturbance of which may contribute to disease onset in coral reef organisms.

Diarrhoeagenic Escherichia coli (DEC) persistently challenges public health in Africa, contributing substantially to the diarrhoeal disease burden. This systematic review and meta-analysis illuminate the distribution and antimicrobial resistance (AMR) patterns of DEC pathotypes across the continent.

The review selectively focused on pathotype-specific studies reporting prevalence and/or AMR of human-derived DEC pathotypes from African nations, excluding data from extra-intestinal, animal, and environmental sources and studies focused on drug and mechanism experiments. Pertinent studies were retrieved from SCOPUS, PubMed, and EBSCOhost, processed with Covidence, and screened in alignment with PRISMA guidelines.

The reviewed studies were predominantly hospital-based (80%) and paediatric-focused (91%), with a meagre 4.4% documenting DEC outbreaks. Seven DEC pathotypes were discerned, with Enteroaggregative E. coli (EAEC) being notably prevalent (43%, 95% CI 30-55%) and Enteroinvasive E. coli (EIEC) least prevalent (24%, 95% CI 17-32%). Identified non-susceptibilities were noted against essential antibiotics including ciprofloxacin, ceftriaxone, and ampicillin, while instances of carbapenem and Extended-Spectrum ß-Lactamase (ESBL) resistance were scarce.

Despite sporadic data on DEC prevalence and AMR in Africa, particularly in community settings, a palpable gap remains in real-time outbreak surveillance and comprehensive data documentation. Augmenting surveillance and embracing advancements in molecular/genomic characterisation techniques are crucial to precisely discerning DEC's actual impact and resistance continuum in Africa.

Helicobacter pylori is a pathogenic bacterium that causes gastritis and gastric carcinoma. Besides gastric complications its potential link with gut-brain axis disruption and neurological disorders has also been reported. The current study investigated the plausible role and its associated molecular mechanism underlying H. pylori mediated gut-brain axis disruption and neuroinflammation leading to neurological modalities like Alzheimer's disease (AD). We have chosen the antimicrobial resistant and susceptible H. pylori strains on the basis of broth dilution method. We have observed the increased inflammatory response exerted by H. pylori strains in the gastric as well as in the neuronal compartment after treatment with Helicobacter pylori derived condition media (HPCM). Further, elevated expression of STAT1, STAT3, and AD-associated proteins- APP and APOE4 was monitored in HPCM-treated neuronal and neuron-astrocyte co-cultured cells. Excessive ROS generation has been found in these cells. The HPCM treatment to LN229 causes astrogliosis, evidenced by increased glial fibrillary acidic protein. Our results indicate the association of STAT3 as an important regulator in the H. pylori-mediated pathogenesis in neuronal cells. Notably, the inhibition of STAT3 by its specific inhibitor, BP-1-102, reduced the expression of pSTAT3 and AD markers in neuronal compartment induced by HPCM. Thus, our study demonstrates that H. pylori infection exacerbates inflammation in AGS cells and modulates the activity of STAT3 regulatory molecules. H. pylori secretome could affect neurological compartments by promoting STAT3 activation and inducing the expression of AD-associated signature markers. Further, pSTAT-3 inhibition mitigates the H. pylori associated neuroinflammation and amyloid pathology.