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Frontiers in Immunology 2019In primary infection with , it has been reported-without consideration of 's functions-that humoral immunity plays no role in the clearance of bacteria. In fact,... (Review)
Review
In primary infection with , it has been reported-without consideration of 's functions-that humoral immunity plays no role in the clearance of bacteria. In fact, targets and suppresses several aspects of humoral immunity, including B cell lymphopoiesis, B cell activation, and IgG production. In particular, the suppression of IgG-secreting plasma cell maintenance allows the persistence of in tissues. Therefore, the critical role(s) of humoral immunity in the response to infection, especially at the late phase, should be re-investigated. The suppression of IgG plasma cell memory strongly hinders vaccine development against non-typhoidal (NTS) because can also reduce humoral immune memory against other bacteria and viruses, obtained from previous vaccination or infection. We propose a new vaccine against that would not impair humoral immunity, and which could also be used as a treatment for antibody-dependent autoimmune diseases to deplete pathogenic long-lived plasma cells, by utilizing the 's own suppression mechanism of humoral immunity.
Topics: Animals; B-Lymphocytes; Host-Pathogen Interactions; Humans; Immunity, Humoral; Plasma Cells; Salmonella; Salmonella Infections
PubMed: 32038650
DOI: 10.3389/fimmu.2019.03155 -
Microbiology (Reading, England) Nov 2018Global Salmonella infection, especially in developing countries, is a health and economic burden. The use of antibiotic drugs in treating the infection is proving less... (Review)
Review
Global Salmonella infection, especially in developing countries, is a health and economic burden. The use of antibiotic drugs in treating the infection is proving less effective due to the alarming rise of antibiotic-resistant strains of Salmonella, the effects of antibiotics on normal gut microflora and antibiotic-associated diarrhoea, all of which bring a growing need for alternative treatments, including the use of probiotic micro-organisms. However, there are issues with probiotics, including their potential to be opportunistic pathogens and antibiotic-resistant carriers, and their antibiotic susceptibility if used as complementary therapy. Clinical trials, animal trials and in vitro investigations into the prophylactic and therapeutic efficacies of probiotics have demonstrated antagonistic properties against Salmonella and other enteropathogenic bacteria. Nonetheless, there is a need for further studies into the potential mechanisms, efficacy and mode of delivery of yeast probiotics in Salmonella infections. This review discusses Salmonella infections and treatment using antibiotics and probiotics.
Topics: Anti-Bacterial Agents; Biofilms; Drug Resistance, Multiple, Bacterial; Gastrointestinal Microbiome; Humans; Probiotics; Salmonella; Salmonella Infections
PubMed: 30136920
DOI: 10.1099/mic.0.000709 -
Immunology Letters Oct 2017Salmonella infection causes morbidity and mortality throughout the world with the host immune response varying depending on whether the infection is acute and limited,... (Review)
Review
Salmonella infection causes morbidity and mortality throughout the world with the host immune response varying depending on whether the infection is acute and limited, or systemic and chronic. Additionally, Salmonella bacteria have evolved multiple mechanisms to avoid or subvert immunity to its own benefit and often the anatomical location of infection plays a role in both the immune response and bacterial fate. Here, we provide an overview of the interplay between the immune system and Salmonella, while discussing how different host and bacterial factors influence the outcome of infection.
Topics: Adaptive Immunity; Animals; Host-Pathogen Interactions; Humans; Immune System; Immunity, Innate; Immunomodulation; Salmonella; Salmonella Infections; Salmonella Infections, Animal
PubMed: 28720334
DOI: 10.1016/j.imlet.2017.07.006 -
Clinical Microbiology Reviews Jan 2019The ability of pathogenic bacteria to affect higher organisms and cause disease is one of the most dramatic properties of microorganisms. Some pathogens can establish... (Review)
Review
The ability of pathogenic bacteria to affect higher organisms and cause disease is one of the most dramatic properties of microorganisms. Some pathogens can establish transient colonization only, but others are capable of infecting their host for many years or even for a lifetime. Long-term infection is called persistence, and this phenotype is fundamental for the biology of important human pathogens, including , , and Both typhoidal and nontyphoidal serovars of the species can cause persistent infection in humans; however, as these two groups cause clinically distinct diseases, the characteristics of their persistent infections in humans differ significantly. Here, following a general summary of pathogenicity, host specificity, epidemiology, and laboratory diagnosis, I review the current knowledge about persistence and discuss the relevant epidemiology of persistence (including carrier rate, duration of shedding, and host and pathogen risk factors), the host response to persistence, genes involved in this lifestyle, as well as genetic and phenotypic changes acquired during prolonged infection within the host. Additionally, I highlight differences between the persistence of typhoidal and nontyphoidal strains in humans and summarize the current gaps and limitations in our understanding, diagnosis, and curing of persistent infections.
Topics: Carrier State; Humans; Risk Factors; Salmonella Infections; Salmonella enterica; Serogroup
PubMed: 30487167
DOI: 10.1128/CMR.00088-18 -
Clinical Microbiology Reviews Oct 2015Salmonella enterica infections are common causes of bloodstream infection in low-resource areas, where they may be difficult to distinguish from other febrile illnesses... (Review)
Review
Salmonella enterica infections are common causes of bloodstream infection in low-resource areas, where they may be difficult to distinguish from other febrile illnesses and may be associated with a high case fatality ratio. Microbiologic culture of blood or bone marrow remains the mainstay of laboratory diagnosis. Antimicrobial resistance has emerged in Salmonella enterica, initially to the traditional first-line drugs chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole. Decreased fluoroquinolone susceptibility and then fluoroquinolone resistance have developed in association with chromosomal mutations in the quinolone resistance-determining region of genes encoding DNA gyrase and topoisomerase IV and also by plasmid-mediated resistance mechanisms. Resistance to extended-spectrum cephalosporins has occurred more often in nontyphoidal than in typhoidal Salmonella strains. Azithromycin is effective for the management of uncomplicated typhoid fever and may serve as an alternative oral drug in areas where fluoroquinolone resistance is common. In 2013, CLSI lowered the ciprofloxacin susceptibility breakpoints to account for accumulating clinical, microbiologic, and pharmacokinetic-pharmacodynamic data suggesting that revision was needed for contemporary invasive Salmonella infections. Newly established CLSI guidelines for azithromycin and Salmonella enterica serovar Typhi were published in CLSI document M100 in 2015.
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Humans; Salmonella; Salmonella Infections
PubMed: 26180063
DOI: 10.1128/CMR.00002-15 -
Nature Jun 2021Ubiquitylation is a widespread post-translational protein modification in eukaryotes and marks bacteria that invade the cytosol as cargo for antibacterial autophagy. The...
Ubiquitylation is a widespread post-translational protein modification in eukaryotes and marks bacteria that invade the cytosol as cargo for antibacterial autophagy. The identity of the ubiquitylated substrate on bacteria is unknown. Here we show that the ubiquitin coat on Salmonella that invade the cytosol is formed through the ubiquitylation of a non-proteinaceous substrate, the lipid A moiety of bacterial lipopolysaccharide (LPS), by the E3 ubiquitin ligase ring finger protein 213 (RNF213). RNF213 is a risk factor for moyamoya disease, which is a progressive stenosis of the supraclinoid internal carotid artery that causes stroke (especially in children). RNF213 restricts the proliferation of cytosolic Salmonella and is essential for the generation of the bacterial ubiquitin coat, both directly (through the ubiquitylation of LPS) and indirectly (through the recruitment of LUBAC, which is a downstream E3 ligase that adds M1-linked ubiquitin chains onto pre-existing ubiquitin coats). In cells that lack RNF213, bacteria do not attract ubiquitin-dependent autophagy receptors or induce antibacterial autophagy. The ubiquitylation of LPS on Salmonella that invade the cytosol requires the dynein-like core of RNF213, but not its RING domain. Instead, ubiquitylation of LPS relies on an RZ finger in the E3 shell. We conclude that ubiquitylation extends beyond protein substrates and that ubiquitylation of LPS triggers cell-autonomous immunity, and we postulate that non-proteinaceous substances other than LPS may also become ubiquitylated.
Topics: Adenosine Triphosphatases; Animals; Autophagy; Cell Line; HeLa Cells; Humans; Lipopolysaccharides; Mice; RING Finger Domains; Salmonella Infections; Salmonella typhimurium; Ubiquitin; Ubiquitin-Protein Ligases; Ubiquitination
PubMed: 34012115
DOI: 10.1038/s41586-021-03566-4 -
Science (New York, N.Y.) Dec 2018Many bacterial infections are hard to treat and tend to relapse, possibly due to the presence of antibiotic-tolerant persisters. In vitro, persister cells appear to be...
Many bacterial infections are hard to treat and tend to relapse, possibly due to the presence of antibiotic-tolerant persisters. In vitro, persister cells appear to be dormant. After uptake of species by macrophages, nongrowing persisters also occur, but their physiological state is poorly understood. In this work, we show that persisters arising during macrophage infection maintain a metabolically active state. Persisters reprogram macrophages by means of effectors secreted by the pathogenicity island 2 type 3 secretion system. These effectors dampened proinflammatory innate immune responses and induced anti-inflammatory macrophage polarization. Such reprogramming allowed nongrowing cells to survive for extended periods in their host. Persisters undermining host immune defenses might confer an advantage to the pathogen during relapse once antibiotic pressure is relieved.
Topics: Animals; Anti-Bacterial Agents; Cells, Cultured; Drug Resistance, Bacterial; Female; Genomic Islands; Host-Pathogen Interactions; Immunity, Innate; Macrophages; Mice; Mice, Inbred C57BL; Recurrence; Salmonella Infections; Salmonella typhimurium; Type III Secretion Systems
PubMed: 30523110
DOI: 10.1126/science.aat7148 -
The Lancet. Infectious Diseases Dec 2019Non-typhoidal salmonella invasive disease is a major cause of global morbidity and mortality. Malnourished children, those with recent malaria or sickle-cell anaemia,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Non-typhoidal salmonella invasive disease is a major cause of global morbidity and mortality. Malnourished children, those with recent malaria or sickle-cell anaemia, and adults with HIV infection are at particularly high risk of disease. We sought to estimate the burden of disease attributable to non-typhoidal salmonella invasive disease for the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017.
METHODS
We did a systematic review of scientific databases and grey literature, and estimated non-typhoidal salmonella invasive disease incidence and mortality for the years 1990 to 2017, by age, sex, and geographical location using DisMod-MR, a Bayesian meta-regression tool. We estimated case fatality by age, HIV status, and sociodemographic development. We also calculated the HIV-attributable fraction and estimated health gap metrics, including disability-adjusted life-years (DALYs).
FINDINGS
We estimated that 535 000 (95% uncertainty interval 409 000-705 000) cases of non-typhoidal salmonella invasive disease occurred in 2017, with the highest incidence in sub-Saharan Africa (34·5 [26·6-45·0] cases per 100 000 person-years) and in children younger than 5 years (34·3 [23·2-54·7] cases per 100 000 person-years). 77 500 (46 400-123 000) deaths were estimated in 2017, of which 18 400 (12 000-27 700) were attributable to HIV. The remaining 59 100 (33 300-98 100) deaths not attributable to HIV accounted for 4·26 million (2·38-7·38) DALYs in 2017. Mean all-age case fatality was 14·5% (9·2-21·1), with higher estimates among children younger than 5 years (13·5% [8·4-19·8]) and elderly people (51·2% [30·2-72·9] among those aged ≥70 years), people with HIV infection (41·8% [30·0-54·0]), and in areas of low sociodemographic development (eg, 15·8% [10·0-22·9] in sub-Saharan Africa).
INTERPRETATION
We present the first global estimates of non-typhoidal salmonella invasive disease that have been produced as part of GBD 2017. Given the high disease burden, particularly in children, elderly people, and people with HIV infection, investigating the sources and transmission pathways of non-typhoidal salmonella invasive disease is crucial to implement effective preventive and control measures.
FUNDING
Bill & Melinda Gates Foundation.
Topics: Female; Geography, Medical; Global Burden of Disease; Humans; Incidence; Male; Prevalence; Risk Factors; Salmonella; Salmonella Infections; Socioeconomic Factors
PubMed: 31562022
DOI: 10.1016/S1473-3099(19)30418-9 -
Science (New York, N.Y.) Jul 2020The guanosine triphosphatase (GTPase) Rab32 coordinates a cell-intrinsic host defense mechanism that restricts the replication of intravacuolar pathogens such as Here,...
The guanosine triphosphatase (GTPase) Rab32 coordinates a cell-intrinsic host defense mechanism that restricts the replication of intravacuolar pathogens such as Here, we show that this mechanism requires aconitate decarboxylase 1 (IRG1), which synthesizes itaconate, a metabolite with antimicrobial activity. We find that Rab32 interacts with IRG1 on infection and facilitates the delivery of itaconate to the -containing vacuole. Mice defective in IRG1 rescued the virulence defect of a serovar Typhimurium mutant specifically defective in its ability to counter the Rab32 defense mechanism. These studies provide a link between a metabolite produced in the mitochondria after stimulation of innate immune receptors and a cell-autonomous defense mechanism that restricts the replication of an intracellular bacterial pathogen.
Topics: Animals; Cell Line; Host-Pathogen Interactions; Humans; Hydro-Lyases; Mice; Salmonella Infections; Salmonella enterica; Salmonella typhimurium; Succinates; Virulence; rab GTP-Binding Proteins
PubMed: 32703879
DOI: 10.1126/science.aaz1333 -
MSystems Feb 2023The spread of multidrug-resistant zoonotic pathogens, such as Salmonella, within livestock is of concern for food safety. The spread of Salmonella on the farm is...
The spread of multidrug-resistant zoonotic pathogens, such as Salmonella, within livestock is of concern for food safety. The spread of Salmonella on the farm is escalated by superspreaders, which shed the pathogen at high numbers with their feces. However, there are currently no biomarkers to identify potential superspreaders. Kempf and coworkers determined that a potent early inflammatory response to Salmonella infection and changes in the microbiota composition are associated with the superspreader phenotype in pigs (F. Kempf, G. Cordoni, A.M. Chaussé, R. Drumo, et al., , in press, https://doi.org/10.1128/msystems.00852-22). Since these biomarkers only develop during Salmonella infection, additional work is needed to predict animals that have the potential to become superspreaders.
Topics: Animals; Swine; Salmonella Infections; Salmonella; Microbiota; Feces
PubMed: 36815796
DOI: 10.1128/msystems.01199-22