• Salmonella enterica serovar Typhimurium
• host‐pathogen interaction
• human in vitro infection models
• immunocompetent models
• intestinal tissue models
• microfold cells
• organoids

• Humans
• Salmonella typhimurium/pathogenicity
• Salmonella typhimurium/immunology
• Host-Pathogen Interactions/immunology
• Salmonella Infections/immunology
• Salmonella Infections/microbiology
• Macrophages/immunology
• Macrophages/microbiology
• Intestinal Mucosa/immunology
• Intestinal Mucosa/microbiology
• Coculture Techniques

• 270563345 Deutsche Forschungsgemeinschaft
• Deutsche Forschungsgemeinschaft

• pathogenic bacteria
• phase variation
• phenotypic heterogeneity
• phenotypic switching

• Bacteria/genetics
• Bacteria/pathogenicity
• Bacteria/drug effects
• Phenotype
• Biofilms/growth & development
• Humans
• Virulence
• Bacterial Infections/microbiology
• Bacterial Physiological Phenomena
• Drug Resistance, Bacterial
• Anti-Bacterial Agents/pharmacology
• Gene Expression Regulation, Bacterial

• Salmonella
• bacteria interaction
• dysbiosis
• gut bacteria
• pathogen defense

• Humans
• Gastrointestinal Microbiome/immunology
• Gastrointestinal Microbiome/physiology
• Salmonella/immunology
• Salmonella/pathogenicity
• Salmonella Infections/immunology
• Salmonella Infections/prevention & control
• Salmonella Infections/microbiology
• Animals
• Symbiosis/immunology
• Dysbiosis/immunology
• Dysbiosis/microbiology
• Bacteria/immunology
• Bacteria/metabolism

• (2023-0551-01) Chungnam National University

• Johne’s disease
• M cells
• MAP
• Mycobacterium avium subsp. paratuberculosis
• RANKL
• enteroids
• mucosal immunity

• Animals
• Mycobacterium avium subsp. paratuberculosis/physiology
• Salmonella typhimurium/physiology
• Salmonella typhimurium/pathogenicity
• Mice
• Paratuberculosis/microbiology
• Microbial Viability
• Intestinal Mucosa/microbiology
• Cattle
• M Cells

• Salmonella Typhimurium
• eicosanoids
• fatty acids
• lipidomic analysis
• macrophages

• Animals
• Salmonella typhimurium/immunology
• Mice
• Macrophages/immunology
• Macrophages/metabolism
• Macrophages/microbiology
• Mice, Inbred C57BL
• PPAR alpha/metabolism
• PPAR alpha/genetics
• Cecum/microbiology
• Salmonella Infections/immunology
• Salmonella Infections/microbiology
• Salmonella Infections/metabolism
• Mice, Knockout
• Salmonella Infections, Animal/immunology
• Salmonella Infections, Animal/microbiology
• Eicosanoids/metabolism
• Male
• Inflammation/metabolism
• Inflammation/immunology
• Inflammation/microbiology

• R01 AI153325 NIAID NIH HHS
• R01 AI171568 NIAID NIH HHS

• TCS
• antibiotic resistance
• multidrug efflux pumps
• transcriptional regulation

• Brucella
• Escherichia coli
• Listeria
• One Health approach
• Salmonella
• antimicrobial resistance
• food intoxication
• meat borne zoonoses

• Humans
• Animals
• Meat
• Salmonella
• Public Health
• Escherichia coli
• Bacteria

• Salmonella Brandenburg
• abortion
• bovine

• Animals
• Chitin
• Chitinases/genetics
• Chitinases/metabolism
• Mammals
• Mice
• Salmonella enterica/metabolism
• Salmonella typhimurium
• Serogroup
• Virulence Factors/genetics
• Virulence Factors/metabolism

• R01 AI143641 NIAID NIH HHS
• R01 GM112490 NIGMS NIH HHS
• National Institute of Allergy and Infectious Diseases
• National Institute of General Medical Sciences
• Department of Microbiology at the University of Illinois Chicago

• Dublin
• Gallinarum
• Pullorum
• Salmonella
• Typhi
• carrier state
• immunity
• typhoid

The widespread use of antibiotics, especially those with a broad spectrum of activity, has resulted in the development of multidrug resistance in many strains of bacteria, including Salmonella. Salmonella is among the most prevalent causes of intoxication due to the consumption of contaminated food and water. Salmonellosis caused by this pathogen is pharmacologically treated using antibiotics such as fluoroquinolones, ceftriaxone, and azithromycin. This foodborne pathogen developed several molecular mechanisms of resistance both on the level of global and local transcription modulators. The increasing rate of antibiotic resistance in Salmonella poses a significant global concern, and an improved understanding of the multidrug resistance mechanisms in Salmonella is essential for choosing the suitable antibiotic for the treatment of infections. In this review, we summarized the current knowledge of molecular mechanisms that control gene expression related to antibiotic resistance of Salmonella strains. We characterized regulators acting as transcription activators and repressors, as well as two-component signal transduction systems. We also discuss the background of the molecular mechanisms of the resistance to metals, regulators of multidrug resistance to antibiotics, global regulators of the LysR family, as well as regulators of histone-like proteins.

• Salmonella
• antibiotic resistance
• transcription regulators

• Copper oxide nanomaterials
• Haem oxygenase
• Interleukin 8
• Intestine
• Metallothionein
• Mucin 2

The regulation of infection and inflammation by a variety of host peptides may represent an evolutionary failsafe in terms of functional degeneracy and it emphasizes the significance of host defense in survival. Neuropeptides have been demonstrated to have similar antimicrobial activities to conventional antimicrobial peptides with broad-spectrum action against a variety of microorganisms. Neuropeptides display indirect anti-infective capacity via enhancement of the host’s innate and adaptive immune defense mechanisms. However, more recently concerns have been raised that some neuropeptides may have the potential to augment microbial virulence. In this review we discuss the dual role of neuropeptides, perceived as a double-edged sword, with antimicrobial activity against bacteria, fungi, and protozoa but also capable of enhancing virulence and pathogenicity. We review the different ways by which neuropeptides modulate crucial stages of microbial pathogenesis such as adhesion, biofilm formation, invasion, intracellular lifestyle, dissemination, etc., including their anti-infective properties but also detrimental effects. Finally, we provide an overview of the efficacy and therapeutic potential of neuropeptides in murine models of infectious diseases and outline the intrinsic host factors as well as factors related to pathogen adaptation that may influence efficacy.

• adhesion
• antimicrobial activity
• bacterial infections
• defense
• fungal infections
• invasion
• neuropeptides
• pathogenesis
• protozoan infections
• virulence

• Animals
• Humans
• Infections/immunology
• Infections/microbiology
• Infections/therapy
• Molecular Targeted Therapy
• Neuropeptides/immunology
• Virulence

• Salmonella
• Salmonella Typhi
• antimicrobial resistance
• enteric fever diagnosis
• enteric fever surveillance
• typhoid fever diagnosis

• Salmonella
• antacid formulation
• gastric survival
• immune response
• magnesium hydroxide
• sodium bicarbonate

• Codon optimization
• DNA Vaccine
• Genetically modified Salmonella
• Influenza
• Self-destructing

• Animals
• Antibodies, Neutralizing/biosynthesis
• Antibodies, Viral/biosynthesis
• Antigens, Viral/genetics
• Antigens, Viral/immunology
• Female
• Genes, Lethal
• Genetic Engineering/methods
• Humans
• Immunity, Cellular/drug effects
• Immunity, Mucosal/drug effects
• Immunization/methods
• Influenza Vaccines/genetics
• Influenza, Human/immunology
• Influenza, Human/prevention & control
• Influenza, Human/virology
• Mice
• Mice, Inbred BALB C
• Nucleoproteins/genetics
• Nucleoproteins/immunology
• Organisms, Genetically Modified
• Plasmids/chemistry
• Plasmids/metabolism
• Salmonella typhimurium/genetics
• Salmonella typhimurium/immunology
• Transgenes
• Vaccines, DNA/genetics

• R01 AI093348 NIAID NIH HHS

• gut-brain axis
• host response
• microbiota
• neuroimmunity
• visceral afferents

• Intestinal Enteroids
• Mucosal Immunity
• Rotavirus

• gut-associated lymphoid tissue
• homing
• mucosal immunity
• oral immunization
• secretory IgA

Salmonella genus represents the most common foodborne pathogens causing morbidity, mortality, and burden of disease in all regions of the world. The introduction of antimicrobial agents and Salmonella-specific phages has been considered as an effective intervention strategy to reduce Salmonella contamination. However, data from the United States, European countries, and low- and middle-income countries indicate that Salmonella cases are still a commonly encountered cause of bacterial foodborne diseases globally. The control programs have not been successful and even led to the emergence of some multidrug-resistant Salmonella strains. It is known that the host immune system is able to effectively prevent microbial invasion and eliminate microorganisms. However, Salmonella has evolved mechanisms of resisting host physical barriers and inhibiting subsequent activation of immune response through their virulence factors. There has been a high interest in understanding how Salmonella interacts with the host. Therefore, in the present review, we characterize the functions of Salmonella virulence genes and particularly focus on the mechanisms of immune escape in light of evidence from the emerging mainstream literature.

• Salmonella
• immune escape
• immune response
• virulence

• M cell
• Peyer's patch
• SFB
• Salmonella
• gut microbiome
• host-pathogen
• mucosal immunology
• neuro-immune
• nociceptor
• segmentous filamentous bacteria

• Animals
• Epithelium/metabolism
• Female
• Ganglia, Spinal/metabolism
• Ganglia, Spinal/microbiology
• Gastrointestinal Microbiome/physiology
• Host Microbial Interactions/physiology
• Intestinal Mucosa/microbiology
• Male
• Mice
• Mice, Inbred C57BL
• Nociceptors/metabolism
• Nociceptors/physiology
• Peyer's Patches/innervation
• Peyer's Patches/metabolism
• Salmonella Infections/metabolism
• Salmonella typhimurium/metabolism
• Salmonella typhimurium/pathogenicity
• Sensory Receptor Cells/metabolism
• Sensory Receptor Cells/physiology

• R01 DK110559 NIDDK NIH HHS
• R01 AI130019 NIAID NIH HHS
• P30 DK034854 NIDDK NIH HHS
• R01 AI039558 NIAID NIH HHS
• U19 AI113187 NIAID NIH HHS
• DP2 AT009499 NCCIH NIH HHS
• K08 AI108690 NIAID NIH HHS
• K08 DK110532 NIDDK NIH HHS

Schistosoma mansoni threatens hundreds of millions of people in >50 countries. Schistosomulae migrate through the lung and adult worms reside in blood vessels adjacent to the intestinal mucosa. Current candidate vaccines aren’t designed to elicit a mucosal response. We have repurposed an attenuated Salmonella enterica Typhimurium strain (YS1646) to produce such a vaccine targeting Cathepsin B (CatB), a digestive enzyme important for parasite survival. Promoter-Type 3 secretory signal pairs were screened for protein expression in vitro and transfected into YS1646 to generate candidate vaccine strains. Two strains were selected for in vivo evaluation (nirB_SspH1 and SspH1_SspH1). Female C57BL/6 mice were immunized twice, 3 weeks apart, using six strategies: i) saline gavage (control), ii) the ‘empty’ YS1646 vector orally (PO) followed by intramuscular (IM) recombinant CatB (20μg IM rCatB), iii) two doses of IM rCatB, iv) two PO doses of YS1646-CatB, v) IM rCatB then PO YS1646-CatB and vi) PO YS1646-CatB then IM rCatB. Serum IgG responses to CatB were monitored by ELISA. Three weeks after the second dose, mice were challenged with 150 cercariae and sacrificed 7 weeks later to assess adult worm and egg burden (liver and intestine), granuloma size and egg morphology. CatB-specific IgG antibodies were low/absent in the control and PO only groups but rose substantially in other groups (5898-6766ng/mL). The highest response was in animals that received nirB_SspH1 YS1646 PO then IM rCatB. In this group, reductions in worm and intestine/liver egg burden (vs. control) were 93.1% and 79.5%/90.3% respectively (all P < .0001). Granuloma size was reduced in all vaccinated groups (range 32.9–52.8 x10³μm²) and most significantly in the nirB_SspH1 + CatB IM group (34.7±3.4 x10³μm²vs. 62.2±6.1 x10³μm²: vs. control P < .01). Many eggs in the vaccinated animals had abnormal morphology. Targeting CatB using a multi-modality approach can provide almost complete protection against S. mansoni challenge.

Schistosomiasis is a parasitic disease that affects over 250 million people worldwide and over 800 million are at risk of infection. Of the three main species, Schistosoma mansoni is the most widely distributed and is endemic in the Caribbean, South America, and Africa. It causes a chronic disease with severe negative effects on quality of life. Mass drug administration of praziquantel is the only available course of action due to a current lack of vaccines. However, praziquantel does not protect from reinfection. Therefore, a vaccine would be beneficial as a long-term solution to reduce morbidity and transmission of the disease. Our group has repurposed the attenuated YS1646 strain of Salmonella Typhimurium as an oral vaccine vector for the digestive enzyme Cathepsin B of S. mansoni. Oral vaccination followed by an intramuscular dose of recombinant Cathepsin B lead to significant reductions in parasite burden in mice. These animals had the highest titers in serum IgG and intestinal IgA antibodies. This multimodal vaccination approach also elicited both Th1 and Th2 cytokines as seen by the increases in IFNγ and IL-5. Finally, vaccinated mice had reductions in granuloma size along with a higher proportion of morphologically-abnormal eggs. This work demonstrates that a YS1646-based, multimodality, prime-boost immunization schedule can provide nearly complete protection against S. mansoni in a well-established murine model.

• Clostridium difficile
• YS1646
• attenuated Salmonella enterica serovar Typhimurium
• lethal challenge
• toxin A
• toxin B
• vaccine

• Caco-2 cell
• Copper oxide
• Interleukin-8
• Microfold cells
• Mucus
• Nanomaterial
• Nanotoxicology
• TEER
• Translocation

• Biological Transport
• Caco-2 Cells
• Cell Differentiation/drug effects
• Cell Survival/drug effects
• Coculture Techniques/methods
• Copper/chemistry
• Copper/toxicity
• Copper Sulfate/chemistry
• Copper Sulfate/toxicity
• Gastrointestinal Tract/drug effects
• Humans
• Interleukin-8/metabolism
• Intestinal Absorption
• Intestinal Mucosa
• Mucus/cytology
• Nanostructures/chemistry
• Nanostructures/toxicity
• Permeability

• 760813 Horizon 2020
• Tertiary Education Trust Fund

Human intestines contain a heterogeneous collection of cells that include immune, neural and epithelial elements interacting in a highly complex physiology that is challenging to maintain ex vivo. There is an extreme oxygen gradient across the intestinal wall due in part to microbiota in the lumen and close to the gut wall, which complicates the design of tissue culture systems. The current study established the use of an organotypic slice model of human intestinal tissue derived from colonoscopy biopsies to study host-microbial interactions after antibiotic treatment, and the influence of oxygen concentration on gut wall function.

Organotypic slices from human colon biopsies collected during routine colonoscopy provided three-dimensional environments that maintained cellular morphology ex vivo. Biopsy slices were used to study impacts of oxygen concentrations and antibiotic treatments on epithelial proliferation rates, and metabolites from tissue culture supernatants.

Immune function was validated via demonstration of a T lymphocyte response to Salmonella enterica serovar Typhimurium. Following 24 h of Salmonella exposure there was a significant increase in CD3⁺ T-lymphocytes in biopsy slices. Metabolite profiling of tissue culture supernatants validated the influence of antibiotic treatment under varied oxygen culture conditions on both host and microbiome-mediated metabolism. Epithelial health was influenced by oxygen and antibiotic. Increased epithelial proliferation was measured in lowered oxygen conditions (1% = 5.9 mmHg) compared to atmospheric conditions standard at 5000 feet above sea level in Colorado (~17% = 100 mmHg). Antibiotic treatment reduced epithelial proliferation only in 5.9 mmHg oxygen cultured slices.

A human colon organotypic slice model was established for applications ranging from gut epithelial proliferation to enteric pathogen influence on mucosal immune functions ex vivo. The results further support the need to account for oxygen concentration in primary tissue cultures, and that antibiotic use impacts gut-microbe-immune interactions.

• Anti-Bacterial Agents/pharmacology
• Apoptosis
• Cell Proliferation
• Colon/drug effects
• Colon/microbiology
• Colon/physiology
• Humans
• Metabolic Networks and Pathways
• Organ Culture Techniques/methods
• Oxygen/metabolism
• Salmonella typhimurium/drug effects
• Salmonella typhimurium/isolation & purification

• T32 OD012201 NIH HHS
• National Science Foundation
• National Institutes of Health

• Salmonella antigens
• chickens
• ileum
• oral delivery
• polyanhydride nanoparticles

• Adhesiveness
• Animals
• Antibody Formation
• Chickens/immunology
• Chickens/microbiology
• Cytokines/genetics
• Cytokines/metabolism
• Flagella/metabolism
• Fluorescence
• Immunity, Cellular
• Mucus/metabolism
• Nanoparticles/chemistry
• Nanoparticles/ultrastructure
• Polyanhydrides/chemistry
• Porins/metabolism
• RNA, Messenger/genetics
• RNA, Messenger/metabolism
• Salmonella/physiology
• Salmonella Vaccines/immunology
• Surface Properties
• T-Lymphocytes/immunology
• Up-Regulation/genetics
• Vaccination
• Vaccines, Subunit/immunology

Salmonella Typhimurium causes a self-limiting gastroenteritis that may lead to systemic disease. Bacteria invade the small intestine, crossing the intestinal epithelium from where they are transported to the mesenteric lymph nodes (MLNs) within migrating immune cells. MLNs are an important site at which the innate and adaptive immune responses converge but their architecture and function is severely disrupted during S. Typhimurium infection. To further understand host-pathogen interactions at this site, we used mass spectrometry imaging (MSI) to analyse MLN tissue from a murine model of S. Typhimurium infection. A molecule, identified as palmitoylcarnitine (PalC), was of particular interest due to its high abundance at loci of S. Typhimurium infection and MLN disruption. High levels of PalC localised to sites within the MLNs where B and T cells were absent and where the perimeter of CD169⁺ sub capsular sinus macrophages was disrupted. MLN cells cultured ex vivo and treated with PalC had reduced CD4⁺CD25⁺ T cells and an increased number of B220⁺CD19⁺ B cells. The reduction in CD4⁺CD25⁺ T cells was likely due to apoptosis driven by increased caspase-3/7 activity. These data indicate that PalC significantly alters the host response in the MLNs, acting as a decisive factor in infection outcome.

Giardia lamblia is one of the most common infectious protozoans in human that may cause diarrhea in travelers. Searching for antigens that induced effectively protective immunity has become a key point in the development of vaccine against giardiasis.

Mice vaccinated with G. lamblia trophozozite-specific α1-giardin DNA vaccine delivered orally by attenuated Salmonella typhimurium SL7027 elicited 74.2% trophozoite reduction, but only 28% reduction in cyst shedding compared with PBS buffer control. Oral vaccination with Salmonella-delivered cyst-specific CWP2 DNA produced 89% reduction in cysts shedding in feces of vaccinated mice. Significantly, the mice vaccinated with Salmonella-delivered bivalent α1-giardin and CWP2 DNA vaccines produced significant reduction in both trophozoite (79%) and cyst (93%) in feces of vaccinated mice. This parasite reduction is associated with the strong local mucosal IgA secretion and the IgG2a-dominant systemic immune responses in vaccinated mice.

The results demonstrate that bivalent vaccines targeting α1-giardin and CWP2 can protect mice against the colonization of Giardia trophozoite and block the transformation of cyst in host at the same time, and can be used to prevent Giardia infection and block the transmission of giardiasis.

• Animals
• Antibody Formation/immunology
• Cytoskeletal Proteins/immunology
• Feces/microbiology
• Feces/parasitology
• Female
• Fluorescent Antibody Technique
• Giardia lamblia/immunology
• Giardiasis/blood
• Giardiasis/immunology
• Giardiasis/parasitology
• Immunity
• Immunoglobulin G/immunology
• Intestinal Mucosa/parasitology
• Intestinal Mucosa/pathology
• Lymph Nodes/pathology
• Mice, Inbred BALB C
• Plasmids/metabolism
• Protozoan Proteins/immunology
• Salmonella typhimurium/metabolism
• Trophozoites/immunology
• Vaccination
• Vaccines, DNA/immunology

• the National Natural Science Foundation of China

• Salmonella
• Toll-like receptor 5
• flagellin
• secretory IgA

Understanding immune responses elicited by vaccines, together with immune responses required for protection, is fundamental to designing effective vaccines and immunisation programs. This study examines the effects of the route of administration of a live attenuated vaccine on its interactions with, and stimulation of, the murine immune system as well as its ability to increase survival and provide protection from colonisation by a virulent challenge strain. We assess the effect of administration method using the murine model for typhoid, where animals are infected with S. Typhimurium. Mice were vaccinated either intravenously or orally with the same live attenuated S. Typhimurium strain and data were collected on vaccine strain growth, shedding and stimulation of antibodies and cytokines. Following vaccination, mice were challenged with a virulent strain of S. Typhimurium and the protection conferred by the different vaccination routes was measured in terms of challenge suppression and animal survival. The main difference in immune stimulation found in this study was the development of a secretory IgA response in orally-vaccinated mice, which was absent in IV vaccinated mice. While both strains showed similar protection in terms of challenge suppression in systemic organs (spleen and liver) as well as survival, they differed in terms of challenge suppression of virulent pathogens in gut-associated organs. This difference in gut colonisation presents important questions around the ability of vaccines to prevent shedding and transmission. These findings demonstrate that while protection conferred by two vaccines can appear to be the same, the mechanisms controlling the protection can differ and have important implications for infection dynamics within a population.

• Administration, Oral
• Animals
• Antibodies, Bacterial/blood
• Antibodies, Bacterial/immunology
• Bacterial Vaccines/administration & dosage
• Bacterial Vaccines/immunology
• Cytokines/metabolism
• Disease Models, Animal
• Feces/microbiology
• Immunoglobulin G/blood
• Immunoglobulin G/immunology
• Mice
• Salmonella typhimurium/immunology
• Salmonella typhimurium/pathogenicity
• Typhoid Fever/immunology
• Typhoid Fever/microbiology
• Typhoid Fever/mortality
• Typhoid Fever/prevention & control
• Vaccination/methods

• Salmonella infection
• biotin
• colon
• intestine
• transport

• Shigella flexneri
• bioimage analysis
• host–pathogen interactions
• intestinal crypts
• tissue microbiology

Enteric pathogens cause considerable public health concerns worldwide including tropical regions. Here, we review the roles of carbohydrates in the infection strategies of various enteric pathogens including viruses, bacteria and protozoa, which infect the epithelial lining of the human and animal intestine. At host cell entry, enteric viruses, including norovirus, recognize mainly histo-blood group antigens. At the initial step of bacterial infections, carbohydrates also function as receptors for attachment. Here, we describe the function of carbohydrates in infection by Salmonella enterica and several bacterial species that produce a variety of fimbrial adhesions. During invasion by enteropathogenic protozoa, apicomplexan parasites utilize sialic acids or sulfated glycans. Carbohydrates serve as receptors for infection by these microbes; however, their usage of carbohydrates varies depending on the microbe. On the surface of the mucosal tissues of the gastrointestinal tract, various carbohydrate moieties are present and play a crucial role in infection, representing the site of infection or route of access for most microbes. During the infection and/or invasion process of the microbes, carbohydrates function as receptors for various microbes, but they can also function as a barrier to infection. One approach to develop effective prophylactic and therapeutic antimicrobial agents is to modify the drug structure. Another approach is to modify the mode of inhibition of infection depending on the individual pathogen by using and mimicking the interactions with carbohydrates. In addition, similarities in mode of infection may also be utilized. Our findings will be useful in the development of new drugs for the treatment of enteric pathogens.

• bacteria
• carbohydrate
• enteric pathogen
• infection
• protozoa
• virus

• Carrier-state
• Chicken
• Microarray
• Salmonella

• Animals
• Bacterial Adhesion/drug effects
• Bacterial Load
• Caco-2 Cells
• Cecum/drug effects
• Cecum/microbiology
• Cell Line
• Chickens
• Dietary Fiber/administration & dosage
• Dietary Supplements
• Enterocytes/drug effects
• Enterocytes/microbiology
• Epithelial Cells/drug effects
• Epithelial Cells/microbiology
• Humans
• Ileum/drug effects
• Ileum/microbiology
• Ileum/physiopathology
• Intestinal Mucosa/drug effects
• Intestinal Mucosa/microbiology
• Intestinal Mucosa/physiopathology
• Liver/drug effects
• Liver/microbiology
• Pectins/pharmacology
• Plantago/chemistry
• Polysaccharides/pharmacology
• Poultry Diseases/microbiology
• Poultry Diseases/prevention & control
• Salmonella enteritidis/drug effects
• Salmonella enteritidis/physiology
• Salmonella typhimurium/drug effects
• Spleen/drug effects
• Spleen/microbiology
• Swine

• BB/E013651/1 Biotechnology and Biological Sciences Research Council
• BB/G01969X/1 Biotechnology and Biological Sciences Research Council
• BB/I016783/1 Biotechnology and Biological Sciences Research Council

HIV/AIDS is an important public health problem globally. An affordable, easy-to-deliver and protective HIV vaccine is therefore required to curb the pandemic from spreading further. Recombinant Salmonella bacteria can be harnessed to vector HIV antigens or DNA vaccines to the immune system for induction of specific protective immunity. These are capable of activating the innate, humoral and cellular immune responses at both mucosal and systemic compartments. Several studies have already demonstrated the utility of live recombinant Salmonella in delivering expressed foreign antigens as well as DNA vaccines to the host immune system. This review gives an overview of the studies in which recombinant Salmonella bacteria were used to vector HIV/AIDS antigens and DNA vaccines. Most of the recombinant Salmonella-based HIV/AIDS vaccines developed so far have only been tested in animals (mainly mice) and are yet to reach human trials.

• DNA
• HIV/AIDS
• Salmonella
• antigens
• bacteria
• vaccines.
• vectoring

• Health risk benchmark
• QMRA
• Rain harvesting
• Relative risk analysis
• Sustainable water practice

• Agricultural Irrigation
• Cucumis sativus/growth & development
• Cucumis sativus/microbiology
• Drinking Water/microbiology
• Drinking Water/standards
• Food Contamination/analysis
• Humans
• Infections/microbiology
• Lactuca/growth & development
• Lactuca/microbiology
• Solanum lycopersicum/growth & development
• Solanum lycopersicum/microbiology
• Models, Theoretical
• Rain
• Risk Assessment/methods
• United States
• Water
• Water Microbiology

Salmonella Typhi asymptomatic chronic carriage represents a challenge for the diagnosis and prevention of typhoid fever in endemic areas. Such carriers are thought to be reservoirs for further spread of the disease. Gallbladder carriage has been demonstrated to be mediated by biofilm formation on gallstones and by intracellular persistence in the gallbladder epithelium of mice. In addition, both gallstones and chronic carriage have been associated with chronic inflammation and the development of gallbladder carcinoma. However, the pathogenic relationship between typhoid carriage and the development of pre-malignant and/or malignant lesions in the hepatopancreatobiliary system as well as the host-pathogen interactions occurring during chronic carriage remains unclear. In this study, we monitored the histopathological features of chronic carriage up to 1 year post-infection. Chronic cholecystitis and hepatitis ranging from mild to severe were present in infected mice regardless of the presence of gallstones. Biliary epithelial hyperplasia was observed more commonly in the gallbladder of mice with gallstones (uninfected or infected). However, pre-malignant lesions, atypical hyperplasia and metaplasia of the gallbladder and exocrine pancreas, respectively, were only associated with chronic Salmonella carriage. This study has implications regarding the role of Salmonella chronic infection and inflammation in the development of pre-malignant lesions in the epithelium of the gallbladder and pancreas that could lead to oncogenesis.

• Animals
• Chronic Disease
• Gallbladder/microbiology
• Gallbladder/pathology
• Gallbladder Neoplasms/microbiology
• Gallbladder Neoplasms/pathology
• Mice
• Pancreas, Exocrine/microbiology
• Pancreas, Exocrine/pathology
• Pancreatic Neoplasms/microbiology
• Pancreatic Neoplasms/pathology
• Precancerous Conditions/pathology
• Salmonella Infections/pathology
• Salmonella typhimurium
• Time Factors

• R01 AI066208 NIAID NIH HHS
• AI066208 NIAID NIH HHS