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Proteomics. Clinical Applications Jan 2012Salmonella bacteria cause millions of infections and thousands of deaths every year. This pathogen has an unusually broad host range including humans, animals, and even... (Review)
Review
Salmonella bacteria cause millions of infections and thousands of deaths every year. This pathogen has an unusually broad host range including humans, animals, and even plants. During infection, Salmonella expresses a variety of virulence factors and effectors that are delivered into the host cell triggering cellular responses through protein-protein interactions (PPI) with host cell proteins which make the pathogen's invasion and replication possible. To speed up proteomic efforts in elucidating Salmonella-host interactomes, we carried out a survey of the currently published Salmonella-host PPI. Such a list can serve as the gold standard for computational models aimed at predicting Salmonella-host interactomes through integration of large-scale biological data sources. Manual literature and database search of >2200 journal articles and >100 databases resulted in a gold standard list of currently 62 PPI, including primarily interactions of Salmonella proteins with human and mouse proteins. Only six of these interactions were directly retrievable from PPI databases and 16 were highlighted in databases featuring literature extracts. Thus, the literature survey resulted in the most complete interactome available to date for Salmonella. Pathway analysis using Ingenuity and Broad Gene Set Enrichment Analysis (GSEA) software revealed among general pathways such as MAPK signaling in particular those related to cell death as well as cell morphology, turnover, and interactions, in addition to response to not only Salmonella but also other pathogenic - viral and bacterial - infections. The list of interactions is available at http://www.shiprec.org/indicationslist.htm.
Topics: Animals; Apoptosis; Bacterial Proteins; Databases, Protein; Host-Pathogen Interactions; Humans; Intestinal Diseases; Protein Interaction Mapping; Salmonella; Salmonella Infections; Virulence
PubMed: 22213674
DOI: 10.1002/prca.201100083 -
Vaccine Jun 2015Invasive Salmonella infections (typhoidal and non-typhoidal) cause a huge burden of illness estimated at nearly 3.4 million cases and over 600,000 deaths annually... (Review)
Review
Invasive Salmonella infections (typhoidal and non-typhoidal) cause a huge burden of illness estimated at nearly 3.4 million cases and over 600,000 deaths annually especially in resource-limited settings. Invasive non-typhoidal Salmonella (iNTS) infections are particularly important in immunosuppressed populations especially in sub-Saharan Africa, causing a mortality of 20-30% in vulnerable children below 5 years of age. In these settings, where routine surveillance for antimicrobial resistance is rare or non-existent, reports of 50-75% multidrug resistance (MDR) in NTS are common, including strains of NTS also resistant to flouroquinolones and 3rd generation cephalosporins. Typhoid (enteric) fever caused by Salmonella Typhi and Salmonella Paratyphi A remains a major public health problem in many parts of Asia and Africa. Currently over a third of isolates in many endemic areas are MDR, and diminished susceptibility or resistance to fluoroquinolones, the drugs of choice for MDR cases over the last decade is an increasing problem. The situation is particularly worrying in resource-limited settings where the few remaining effective antimicrobials are either unavailable or altogether too expensive to be afforded by either the general public or by public health services. Although the prudent use of effective antimicrobials, improved hygiene and sanitation and the discovery of new antimicrobial agents may offer hope for the management of invasive salmonella infections, it is essential to consider other interventions including the wider use of WHO recommended typhoid vaccines and the acceleration of trials for novel iNTS vaccines. The main objective of this review is to describe existing data on the prevalence and epidemiology of antimicrobial resistant invasive Salmonella infections and how this affects the management of these infections, especially in endemic developing countries.
Topics: Adolescent; Africa; Anti-Bacterial Agents; Asia; Cephalosporin Resistance; Child; Child, Preschool; Developing Countries; Disease Management; Drug Resistance, Bacterial; Fluoroquinolones; Humans; Infant; Prevalence; Salmonella Infections; Salmonella paratyphi A; Salmonella typhi; Typhoid Fever; Typhoid-Paratyphoid Vaccines
PubMed: 25912288
DOI: 10.1016/j.vaccine.2015.03.102 -
Cell Reports Oct 2023Damage to our genome causes acute senescence in mammalian cells, which undergo growth arrest and release a senescence-associated secretory phenotype (SASP) that...
Damage to our genome causes acute senescence in mammalian cells, which undergo growth arrest and release a senescence-associated secretory phenotype (SASP) that propagates the stress response to bystander cells. Thus, acute senescence is a powerful tumor suppressor. Salmonella enterica hijacks senescence through its typhoid toxin, which usurps unidentified factors in the stress secretome of senescent cells to mediate intracellular infections. Here, transcriptomics of toxin-induced senescent cells (TxSCs) and proteomics of their secretome identify the factors as Wnt5a, INHBA, and GDF15. Wnt5a establishes a positive feedback loop, driving INHBA and GDF15 expression. In fibroblasts, Wnt5a and INHBA mediate autocrine senescence in TxSCs and paracrine senescence in naive cells. Wnt5a synergizes with GDF15 to increase Salmonella invasion. Intestinal TxSCs undergo apoptosis without Wnt5a, which is required for establishing intestinal TxSCs. The study reveals how an innate defense against cancer is co-opted by a bacterial pathogen to cause widespread damage and mediate infections.
Topics: Animals; Humans; Cellular Senescence; Typhoid Fever; Salmonella Infections; Neoplasms; Cells, Cultured; Toxins, Biological; Mammals
PubMed: 37792529
DOI: 10.1016/j.celrep.2023.113181 -
Cells Dec 2021Salmonella infection remains one of the major public health problems in the world, with increasing resistance to antibiotics. The resolution is to explore the... (Review)
Review
Salmonella infection remains one of the major public health problems in the world, with increasing resistance to antibiotics. The resolution is to explore the pathogenesis of the infection and search for alternative therapy other than antibiotics. Immune responses to Salmonella infection include innate and adaptive immunity. Flagellin or muramyl dipeptide from Salmonella, recognized by extracellular Toll-like receptors and intracellular nucleotide-binding oligomerization domain2, respectively, induce innate immunity involving intestinal epithelial cells, neutrophils, macrophages, dendric cells and lymphocytes, including natural killer (NK) and natural killer T (NKT) cells. The cytokines, mostly interleukins, produced by the cells involved in innate immunity, stimulate adaptive immunity involving T and B cells. The mucosal epithelium responds to intestinal pathogens through its secretion of inflammatory cytokines, chemokines, and antimicrobial peptides. Chemokines, such as IL-8 and IL-17, recruit neutrophils into the cecal mucosa to defend against the invasion of , but induce excessive inflammation contributing to colitis. Some of the interleukins have anti-inflammatory effects, such as IL-10, while others have pro-inflammatory effects, such as IL-1β, IL-12/IL-23, IL-15, IL-18, and IL-22. Furthermore, some interleukins, such as IL-6 and IL-27, exhibit both pro- and anti-inflammatory functions and anti-microbial defenses. The majority of interleukins secreted by macrophages and lymphocytes contributes antimicrobial defense or protective effects, but IL-8 and IL-10 may promote systemic infection. In this article, we review the interleukins involved in Salmonella infection in the literature.
Topics: Animals; Humans; Immunity; Immunity, Mucosal; Interleukins; Intestines; Salmonella Infections
PubMed: 34943999
DOI: 10.3390/cells10123492 -
Frontiers in Immunology 2019subsp. serovar Typhimurium (. Typhimurium) is a Gram-negative bacterium with a broad host range that causes non-typhoidal salmonellosis in humans. . Typhimurium... (Review)
Review
subsp. serovar Typhimurium (. Typhimurium) is a Gram-negative bacterium with a broad host range that causes non-typhoidal salmonellosis in humans. . Typhimurium infects epithelial cells and macrophages in the small intestine where it replicates in a specialized intracellular niche called the -containing vacuole (SCV) and promotes inflammation of the mucosa to induce typically self-limiting gastroenteritis. Virulence and spread of the bacterium is determined in part by the host individual's ability to limit the infection through innate immune responses at the gastrointestinal mucosa, including programmed cell death. . Typhimurium however, has evolved a myriad of mechanisms to counteract or exploit host responses through the use of Type III Secretion Systems (T3SS), which allow the translocation of virulence (effector) proteins into the host cell for the benefit of optimal bacterial replication and dissemination. T3SS effectors have been found to interact with apoptotic, necroptotic, and pyroptotic cell death cascades, interfering with both efficient clearance of the bacteria and the recruitment of neutrophils or dendritic cells to the area of infection. The interplay of host inflammation, programmed cell death responses, and bacterial defenses in the context of non-typhoidal (NTS) infection is a continuing area of interest within the field, and as such has been reviewed here.
Topics: Animals; Apoptosis; Cell Death; Host-Pathogen Interactions; Humans; Inflammasomes; Necroptosis; Pyroptosis; Salmonella; Salmonella Infections; Signal Transduction
PubMed: 31402916
DOI: 10.3389/fimmu.2019.01758 -
Nature Reviews. Microbiology Apr 2015Salmonellae invasion and intracellular replication within host cells result in a range of diseases, including gastroenteritis, bacteraemia, enteric fever and focal... (Review)
Review
Salmonellae invasion and intracellular replication within host cells result in a range of diseases, including gastroenteritis, bacteraemia, enteric fever and focal infections. In recent years, considerable progress has been made in our understanding of the molecular mechanisms that salmonellae use to alter host cell physiology; through the delivery of effector proteins with specific activities and through the modulation of defence and stress response pathways. In this Review, we summarize our current knowledge of the complex interplay between bacterial and host factors that leads to inflammation, disease and, in most cases, control of the infection by its animal hosts, with a particular focus on Salmonella enterica subsp. enterica serovar Typhimurium. We also highlight gaps in our knowledge of the contributions of salmonellae and the host to disease pathogenesis, and we suggest future avenues for further study.
Topics: Animals; Epithelial Cells; Host-Pathogen Interactions; Humans; Inflammation; Salmonella Infections; Salmonella typhimurium; Stress, Physiological
PubMed: 25749450
DOI: 10.1038/nrmicro3420 -
FEMS Microbiology Reviews May 2012Host-adapted strains of Salmonella enterica cause systemic infections and have the ability to persist systemically for long periods of time and pose significant... (Review)
Review
Host-adapted strains of Salmonella enterica cause systemic infections and have the ability to persist systemically for long periods of time and pose significant public-health problems. Multidrug-resistant S. enterica serovar Typhi (S. Typhi) and nontyphoidal Salmonella (NTS) are on the increase and are often associated with HIV infection. Chronically infected hosts are often asymptomatic and transmit disease to naïve hosts via fecal shedding of bacteria, thereby serving as a critical reservoir for disease. Salmonella utilizes multiple ways to evade and modulate host innate and adaptive immune responses in order to persist in the presence of a robust immune response. Survival in macrophages and modulation of immune cells migration allow Salmonella to evade various immune responses. The ability of Salmonella to persist depends on a balance between immune responses that lead to the clearance of the pathogen and avoidance of damage to host tissues.
Topics: Animals; Asymptomatic Diseases; Carrier State; Chronic Disease; Host-Pathogen Interactions; Humans; Immune Evasion; Macrophages; Salmonella Infections; Salmonella Infections, Animal; Salmonella enterica
PubMed: 22335190
DOI: 10.1111/j.1574-6976.2012.00332.x -
Infection and Immunity Jan 2022Salmonella invades and disrupts gut epithelium integrity, creating an infection-generated electric field that can drive directional migration of macrophages, a process...
Salmonella invades and disrupts gut epithelium integrity, creating an infection-generated electric field that can drive directional migration of macrophages, a process called galvanotaxis. Phagocytosis of bacteria reverses the direction of macrophage galvanotaxis, implicating a bioelectrical mechanism to initiate life-threatening disseminations. The force that drives direction reversal of macrophage galvanotaxis is not understood. One hypothesis is that Salmonella can alter the electrical properties of the macrophages by modifying host cell surface glycan composition, which is supported by the fact that cleavage of surface-exposed sialic acids with a bacterial neuraminidase severely impairs macrophage galvanotaxis, as well as phagocytosis. Here, we utilize N-glycan profiling by nanoLC-chip QTOF mass cytometry to characterize the bacterial neuraminidase-associated compositional shift of the macrophage glycocalyx, which revealed a decrease in sialylated and an increase in fucosylated and high mannose structures. The Salmonella gene, encoding a putative neuraminidase, is required for invasion and internalization in a human colonic epithelial cell infection model. To determine whether NanH is required for the Salmonella infection-dependent direction reversal, we constructed and characterized a deletion mutant and found that NanH is partially required for Salmonella infection in primary murine macrophages. However, compared to wild type Salmonella, infection with the mutant only marginally reduced the cathode-oriented macrophage galvonotaxis, without canceling direction reversal. Together, these findings strongly suggest that while neuraminidase-mediated N-glycan modification impaired both macrophage phagocytosis and galvanotaxis, yet to be defined mechanisms other than NanH may play a more important role in bioelectrical control of macrophage trafficking, which potentially triggers dissemination.
Topics: Animals; Bacterial Proteins; Chemotaxis, Leukocyte; Female; Host-Pathogen Interactions; Macrophages; Male; Mice; Models, Biological; Mutation; Neuraminidase; Phagocytosis; Polysaccharides; Salmonella; Salmonella Infections; Sialic Acids; Virulence
PubMed: 34662214
DOI: 10.1128/IAI.00516-21 -
Journal of Extracellular Vesicles Sep 2022Small extracellular vesicles (sEVs) produced by antigen-presenting cells represent a novel mechanism of cell-to-cell communication. The sEVs have been shown to drive...
Small extracellular vesicles (sEVs) produced by antigen-presenting cells represent a novel mechanism of cell-to-cell communication. The sEVs have been shown to drive Th1-type adaptive immune responses against intracellular infections such as Salmonella. In this study, we have demonstrated that an administration of sEVs produced by Salmonella-infected macrophages to BALB/c mice that were then challenged with Salmonella infection decreased bacterial load in infected animals and led to protection against a lethal dose of Salmonella. Second, the same sEVs induced a robust production of IgA anti-Salmonella antibodies (Abs) in BALB/c mice, including IgA anti-OmpD Abs. These results show that the nanoscale sEVs stimulate adaptive immune responses against intracellular pathogens and that these sEVs can be used to provide animals with complete protection against lethal infection, such as the systemic bacterial infection in immunodeficient BALB/c mice.
Topics: Animals; Antibodies, Bacterial; Extracellular Vesicles; Immunity, Mucosal; Immunoglobulin A; Mice; Mice, Inbred BALB C; Salmonella; Salmonella Infections
PubMed: 36134734
DOI: 10.1002/jev2.12267 -
Clinical and Vaccine Immunology : CVI Sep 2016Salmonellosis remains an important cause of human disease worldwide. While there are several licensed vaccines for Salmonella enterica serovar Typhi, these vaccines are... (Review)
Review
Salmonellosis remains an important cause of human disease worldwide. While there are several licensed vaccines for Salmonella enterica serovar Typhi, these vaccines are generally ineffective against other Salmonella serovars. Vaccines that target paratyphoid and nontyphoidal Salmonella serovars are very much in need. Preclinical evaluation of candidate vaccines is highly dependent on the availability of appropriate scientific tools, particularly animal models. Many different animal models exist for various Salmonella serovars, from whole-animal models to smaller models, such as those recently established in insects. Here, we discuss various mouse, rat, rabbit, calf, primate, and insect models for Salmonella infection, all of which have their place in research. However, choosing the right model is imperative in selecting the best vaccine candidates for further clinical testing. In this minireview, we summarize the various animal models that are used to assess salmonellosis, highlight some of the advantages and disadvantages of each, and discuss their value in vaccine development.
Topics: Animals; Disease Models, Animal; Drug Evaluation, Preclinical; Insecta; Mammals; Primates; Salmonella Infections; Salmonella Vaccines
PubMed: 27413068
DOI: 10.1128/CVI.00258-16