The incidence of infection by nontuberculous mycobacteria, mainly Mycobacterium abscessus, is increasing in patients with cystic fibrosis and other chronic pulmonary diseases, leading to an accelerated lung function decline. In most cases, M. abscessus coinfects Pseudomonas aeruginosa, the most common pathogen in these conditions. However, how these two bacterial species interact during infection remains poorly understood. This study explored their behaviour in three relevant pathogenic settings: dual-species biofilm development using a recently developed method to monitor individual species in dual-species biofilms, coinfection in bronchial epithelial cells, and in vivo coinfection in the Galleria mellonella model. The results demonstrated that both species form stable mixed biofilms and reciprocally inhibit single-biofilm progression. Coinfections in bronchial epithelial cells significantly decreased cell viability, whereas in G. mellonella, coinfections induced lower survival rates than individual infections. Analysis of the immune response triggered by each bacterium in bronchial epithelial cell assays and G. mellonella larvae revealed that P. aeruginosa induces the overexpression of proinflammatory and melanization cascade responses, respectively. In contrast, M. abscessus and P. aeruginosa coinfection significantly inhibited the immune response in both models, resulting in worse consequences for the host than those generated by a single P. aeruginosa infection. Overall, this study highlights the novel role of M. abscessus in suppressing immune responses during coinfection with P. aeruginosa, emphasizing the clinical implications for the management of cystic fibrosis and other pulmonary diseases. Understanding these interactions could inform the development of new therapeutic strategies to mitigate the severity of coinfections in vulnerable patients.

Helicobacter pylori (H. pylori) is a gram-negative, spiral-shaped bacterium that colonizes the human gastric mucosa, leading to various gastric diseases. H. pylori infection has become a pressing public health issue that affects more than 50% of the human population worldwide, almost 40 years after its discovery. Traditional treatments, based on the use of bismuth-based triple and quadruple therapies, are effective while facing a series of problems, such as difficulty in patient compliance, the rise of antibiotic resistance, and possible recurrence of infection. Therefore, the development of an efficacious vaccine against H. pylori would be extremely urgent. This review mainly elaborates on the pathogenic mechanism and immune evasion mechanism of H. pylori, as well as various strategies adopted in vaccine development, including whole-cell vaccines, subunit vaccines, DNA vaccines, and live vector vaccines. Animal studies and clinical trials demonstrate that H. pylori vaccines significantly reduce bacterial load and provide cellular immunity over some time. Multiple studies have clarified the advantages and limitations of each candidate vaccine. Although the development of H. pylori vaccines provides benefits to reduce the global burden, there are still significant challenges to developing vaccines in safety, efficacy, and availability. Overcoming these challenges, along with the advancement of vaccine technology, can better prevent and treat H. pylori infection.

Glaesserella parasuis (G. parasuis) is the primary pathogen responsible for Glässer's disease and poses a significant threat to the global pig industry. MicroRNAs are a class of short, endogenous, single-stranded noncoding RNAs that play crucial roles in inflammation, apoptosis, proliferation, differentiation, and invasion in various organisms. This study analyzed the characteristics of porcine alveolar macrophage (PAM) cells infected with G. parasuis through the knockdown and overexpression of ssc-miR-129a-3p. We constructed a cellular model with ssc-miR-129a-3p knockdown invaded by G. parasuis strain XX0306, screening 160 differentially expressed genes via high-throughput sequencing. GO enrichment analysis revealed that 376 GO entries were enriched. KEGG enrichment analysis found that mRNA target genes were enriched in 17 cell signaling pathways, including G protein-coupled components, PPAR, and other signaling pathways that can mediate inflammatory pathways. By examining the expression of relevant inflammatory factors and signaling pathways, we elucidated the molecular mechanisms through which ssc-miR-129a-3p targets the TLR4/NF-κB signaling pathway to regulate inflammatory injury. This study establishes a foundation for further research into the role of miRNA in the pathogenesis of Glässer disease and is highly significant for the prevention and control of bacterial diseases within the pig industry.

Long-term exposure to high ammonia concentrations could severely impact chicken health. On the other hand, luteolin has been shown to protect against ammonia poisoning. Although phosphorylation is critically involved in toxicity induction, the specific role of phosphorylated proteins in ammonia poisoning remains unclear. Herein, we constructed an in vitro model to study chicken ammonia poisoning and also analyzed the protective effects of luteolin. Specifically, a combined series of organic techniques such as protein extraction, enzyme digestion, modified peptide enrichment, Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) analysis, and bioinformatics analysis were employed for a quantitative omics study of phosphorylation modification in three groups of samples. Our findings revealed thousands of Differentially Expressed Proteins (DEPs). The differentially expressed modified proteins were subjected to GO classification, KEGG pathway analysis, cluster analysis, and protein interaction analysis, revealing the detoxification mechanism encompassed mitochondrial maintenance, signal transduction, transcriptional regulation, and cytoskeleton regulation. In the process, mitochondria and Golgi apparatus were the key organelles. Furthermore, the AKT1/FOXO signaling pathway and Heat Shock Proteins (HSPs) were the key core modifiers of the proteins. We hope that our findings will provide a theoretical basis and experimental support for future research on luteolin's detoxification mechanism against ammonia poisoning.

Gastric cancer remains a significant global health challenge, with Helicobacter pylori (H. pylori) recognized as a major etiological agent, affecting an estimated 50% of the world's population. There has been a rapidly expanding knowledge of the molecular and pathogenetic mechanisms of H. pylori over the decades. This review summarizes the latest research advances to elucidate the molecular mechanisms underlying the H. pylori infection in gastric carcinogenesis. Our investigation of the molecular mechanisms reveals a complex network involving STAT3, NF-κB, Hippo, and Wnt/β-catenin pathways, which are dysregulated in gastric cancer caused by H. pylori. Furthermore, we highlight the role of H. pylori in inducing oxidative stress, DNA damage, chronic inflammation, and cell apoptosis-key cellular events that pave the way for carcinogenesis. Emerging evidence also suggests the effect of H. pylori on the tumor microenvironment and its possible implications for cancer immunotherapy. This review synthesizes the current knowledge and identifies gaps that warrant further investigation. Despite the progress in our previous knowledge of the development in H. pylori-induced gastric cancer, a comprehensive investigation of H. pylori's role in gastric cancer is crucial for the advancement of prevention and treatment strategies. By elucidating these mechanisms, we aim to provide a more in-depth insights for the study and prevention of H. pylori-related gastric cancer.

Helicobacter pylori infects roughly half the world's population, causing gastritis, peptic ulcers, and gastric cancer in a subset. These pathologies occur in response to a chronic inflammatory state, but it is not fully understood how H. pylori controls this process. We characterized the inflammatory response of H. pylori mutants that cannot produce the quorum sensing molecule autoinducer 2 (AI-2) by deleting the gene for the AI-2 synthase, luxS. Our work shows that H. pylori luxS mutants colonize the stomach normally but recruit high numbers of CD4+ T cells to the stomach during chronic infection. This increase in the number of CD4+ T cells correlated with elevated expression of CXCL9, a chemokine important for T cell recruitment. Together, our results suggest that H. pylori may utilize AI-2 signaling to modulate the inflammatory response during chronic infection.

Many bacteria signal to each other using quorum sensing signals. One type of signal is called autoinducer 2 (AI-2), which is produced and sensed by the LuxS enzyme found in many bacteria, including the gastric pathogen Helicobacter pylori. H. pylori establishes chronic infections that last for decades and lead to serious disease outcomes. How AI-2 signaling and LuxS contribute to chronic H. pylori infection has not been studied. In this work, we analyzed how loss of H. pylori-created AI-2, via mutation of luxS, affects H. pylori chronic infection. luxS mutants did not have significant colonization defects, similar to their reported phenotype during early infection, but they did have high stomach levels of effector and regulatory T cells and T-cell-recruiting chemokines. These results suggest that H. pylori LuxS may play more of a role in modulating the immune response versus colonization.

The role of microbiota in human health and disease is becoming increasingly clear as a result of modern microbiome studies in recent decades. The gastrointestinal tract is the major habitat for microbiota in the human body. This microbiota comprises several trillion microorganisms, which is equivalent to almost ten times the total number of cells of the human host. Helicobacter pylori is a known pathogen that colonizes the gastric mucosa of almost half of the world population. H. pylori is associated with several gastric diseases, including gastric cancer (GC) development. However, the impact of the gastric microbiota in the colonization, chronic infection, and pathogenesis is still not fully understood. Several studies have documented qualitative and quantitative changes in the microbiota's composition in the presence or absence of this pathogen. Among the diverse microflora in the stomach, the Firmicutes represent the most notable. Bacteria such as Prevotella sp., Clostridium sp., Lactobacillus sp., and Veillonella sp. were frequently found in the healthy human stomach. In contrast, H.pylori is very dominant during chronic gastritis, increasing the proportion of Proteobacteria in the total microbiota to almost 80%, with decreasing relative proportions of Firmicutes. Likewise, H. pylori and Streptococcus are the most abundant bacteria during peptic ulcer disease. While the development of H. pylori-associated intestinal metaplasia is accompanied by an increase in Bacteroides, the stomachs of GC patients are dominated by Firmicutes such as Lactobacillus and Veillonella, constituting up to 40% of the total microbiota, and by Bacteroidetes such as Prevotella, whereas the numbers of H. pylori are decreasing. This review focuses on some of the consequences of changes in the gastric microbiota and the function of probiotics to modulate H. pylori infection and dysbiosis in general.

Helicobacter pylori (H. pylori) may be present in the intestinal mucosa of patients with inflammatory bowel disease (IBD), which is a chronic inflammation of the gastrointestinal tract. The role of H. pylori in the pathogenesis of IBD remains unclear. In this study, bioinformatics techniques were used to investigate the correlation and co-pathogenic pathways between H. pylori and IBD.

The following matrix data were downloaded from the GEO database: H. pylori-associated gastritis, GSE233973 and GSE27411; and IBD, GSE3365 and GSE179285. Differential gene analysis was performed via the limma software package in the R environment. A protein-protein interaction (PPI) network of DEGs was constructed via the STRING database. Cytoscape software, through the CytoHubba plugin, filters the PPI subnetwork and identifies Hub genes. Validation of the Hub genes was performed in the validation set. Immune analysis was conducted via the CIBERSORT algorithm. Transcription factor interaction and small molecule drug analyses of the Hub genes were also performed.

Using the GSE233973 and GSE3365 datasets, 151 differentially expressed genes (DEGs) were identified. GO enrichment analysis revealed involvement in leukocyte migration and chemotaxis, response to lipopolysaccharides, response to biostimulatory stimuli, and regulation of interleukin-8 (IL-8) production. Ten Hub genes (TLR4, IL10, CXCL8, IL1B, TLR2, CXCR2, CCL2, IL6, CCR1 and MMP-9) were identified via the PPI network and Cytoscape software. Enrichment analysis of the Hub genes focused on the lipopolysaccharide response, bacterial molecular response, biostimulatory response and leukocyte movement. Validation using the GSE27411 and GSE179285 datasets revealed that MMP-9 was significantly upregulated in both the H. pylori and IBD groups. The CIBERSORT algorithm revealed immune infiltration differences between the control and disease groups of IBD patients. Additionally, the CMap database identified the top 11 small molecule compounds across 10 cell types, including TPCA-1, AS-703026 and memantine, etc.

Our study revealed the co-pathogenic mechanism between H. pylori and IBD and identified 10 Hub genes related to cellular immune regulation and signal transduction. The expression of MMP-9 is significantly upregulated in both H. pylori infection and IBD. This study provides a new perspective for exploring the prevention and treatment of H. pylori infection and IBD.

Several single-nucleotide polymorphisms (SNPs) in human chromosomes are known to predispose to cancer. However, cancer-associated SNPs in bacterial pathogens were unknown until discovered in the stomach pathogen Helicobacter pylori. Those include an alanine-threonine polymorphism in the EPIYA-B phosphorylation motif of the injected effector protein CagA that affects cancer risk by modifying inflammatory responses and loss of host cell polarity. A serine-to-leucine change in serine protease HtrA is associated with boosted proteolytic cleavage of epithelial junction proteins and introduction of DNA double-strand breaks (DSBs) in host chromosomes, which co-operatively elicit malignant alterations. In addition, H. pylori genome-wide association studies (GWAS) identified several other SNPs potentially associated with increased gastric cancer (GC) risk. Here we discuss the clinical importance, evolutionary origin, and functional advantage of the H. pylori SNPs. These exciting new data highlight cancer-associated SNPs in bacteria, which should be explored in more detail in future studies.

In recent years, cancer immunotherapy has undergone a transformative shift toward personalized and targeted therapeutic strategies. Bacteria-derived outer membrane vesicles (OMVs) have emerged as a promising and adaptable platform for cancer immunotherapy due to their unique properties, including natural immunogenicity and the ability to be engineered for specific therapeutic purposes. In this review, a comprehensive overview is provided of state-of-the-art techniques and methodologies employed in the engineering of versatile OMVs for cancer immunotherapy. Beginning by exploring the biogenesis and composition of OMVs, unveiling their intrinsic immunogenic properties for therapeutic appeal. Subsequently, innovative approaches employed to engineer OMVs are delved into, ranging from the genetic engineering of parent bacteria to the incorporation of functional molecules. The importance of rational design strategies is highlighted to enhance the immunogenicity and specificity of OMVs, allowing tailoring for diverse cancer types. Furthermore, insights into clinical studies and potential challenges utilizing OMVs as cancer vaccines or adjuvants are also provided, offering a comprehensive assessment of the current landscape and future prospects. Overall, this review provides valuable insights for researchers involved in the rapidly evolving field of cancer immunotherapy, offering a roadmap for harnessing the full potential of OMVs as a versatile and adaptable platform for cancer treatment.

Bacterial lipoproteins are post-translationally modified with acyl chains, anchoring these proteins to bacterial membranes. In Gram-negative bacteria, three enzymes complete the modifications. Lgt (which adds two acyl chains) and LspA (which removes the signal peptide) are essential. Lnt (which adds a third acyl chain) is not essential in certain bacteria including Francisella tularensis, Neisseria gonorrhoeae, and Acinetobacter baumannii. Deleting lnt results in mild to severe physiologic changes. We previously showed lnt is not essential for Helicobacter pylori growth in vitro. Here, the physiologic consequences of deleting lnt in H. pylori and the role of Lnt in the host response to H. pylori were examined using in vitro and in vivo models. Comparing wild-type, Δlnt, and complemented mutant H. pylori, no changes in growth rates or sensitivity to acid or antibiotics were observed. Since deleting lnt changes the number of acyl chains on lipoproteins and the number of acyl chains on lipoproteins impacts the innate immune response through Toll-like receptor 2 (TLR2) signaling, primary human gastric epithelial cells were treated with a purified lipoprotein from wild-type or lnt mutant H. pylori. Differential gene expression analysis indicated that lipoprotein from the lnt mutant induced a more robust TLR2 response. In a complementary approach, we infected wild-type and Tlr2-/- mice and found that both the wild-type and complemented mutant strains successfully colonized the animals. However, the lnt mutant strain was unable to colonize either mouse strain. These results show that lnt is essential for H. pylori colonization and identifies lipoprotein synthesis as a target for therapeutic intervention.

The microbiota actively and extensively participates in the regulation of human metabolism, playing a crucial role in the development of metabolic diseases. Helicobacter pylori (H. pylori), when colonizing gastric epithelial cells, not only induces local tissue inflammation or malignant transformation but also leads to systemic and partial changes in host metabolism. These shifts can be mediated through direct contact, toxic components, or indirect immune responses. Consequently, they influence various molecular metabolic events that impact nutritional status and iron absorption in the host. Unraveling the intricate and diverse molecular interaction links between H. pylori and human metabolism modulation is essential for understanding pathogenesis mechanisms and developing targeted treatments for related diseases. However, significant challenges persist in comprehensively understanding the complex association networks among H. pylori itself, the infected host's status, the host microbiome, and the immune response. Previous metabolomics research has indicated that H. pylori infection and eradication may selectively shape the metabolite and microbial profiles of gastric lesions. Yet, it remains largely unknown how these diverse metabolic pathways, including isovaleric acid, cholesterol, fatty acids, and phospholipids, specifically modulate gastric carcinogenesis or affect the host's serum metabolism, consequently leading to the development of metabolic-associated diseases. The direct contribution of H. pylori to metabolisms still lacks conclusive evidence. In this review, we summarize recent advances in clinical evidence highlighting associations between chronic H. pylori infection and metabolic diseases, as well as its potential molecular regulatory patterns.

Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disease that causes multi-organ complications, seriously affecting patients' quality of life and survival. Understanding its pathogenesis remains challenging, with current clinical treatment regimens often proving ineffective.

In this study, we established a mouse model of T2DM and employed 16s rDNA sequencing to detect changes in the species and structure of gut flora. Additionally, we used UPLC-Q-TOF-MS to identify changes in urinary metabolites of T2DM mice, analyzed differential metabolites and constructed differential metabolic pathways. Finally, we used Pearman correlation analysis to investigate the relationship between intestinal flora and differential metabolites in T2DM mice, aiming to elucidate the pathogenesis of T2DM and provide an experimental basis for its clinical treatment.

Our findings revealed a reduction in both the species diversity and abundance of intestinal flora in T2DM mice, with significantly decreased levels of beneficial bacteria such as Lactobacillus and significantly increased levels of harmful bacteria such as Helicobacter pylori. Urinary metabolomics results identified 31 differential metabolites between T2DM and control mice, including Phosphatidylcholine, CDP-ethanolamine and Leukotriene A4, which may be closely associated with the glycerophospholipid and arachidonic acid pathways. Pearman correlation analysis showed a strong correlation between dopamine and gonadal, estradiol and gut microbiota, may be a novel direction underlying T2DM.

In conclusion, our study suggests that alterations in gut microbiota and urinary metabolites are characteristic features of T2DM in mice. Furthermore, a strong correlation between dopamine, estradiol and gut microbiota, may be a novel direction underlying T2DM, the aim is to provide new ideas for clinical treatment and basic research.

Helicobacter pylori is a prevalent pathogen, which affects more than 40% of the global population. It colonizes the human stomach and persists in its host for several decades or even a lifetime, if left untreated. The persistent infection has been linked to various gastric diseases, including gastritis, peptic ulcers, and an increased risk for gastric cancer. H. pylori infection triggers a strong immune response directed against the bacterium associated with the infiltration of innate phagocytotic immune cells and the induction of a Th1/Th17 response. Even though certain immune cells seem to be capable of controlling the infection, the host is unable to eliminate the bacteria as H. pylori has developed remarkable immune evasion strategies. The bacterium avoids its killing through innate recognition mechanisms and manipulates gastric epithelial cells and immune cells to support its persistence. This chapter focuses on the innate and adaptive immune response induced by H. pylori infection, and immune evasion strategies employed by the bacterium to enable persistent infection.