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Scientific Reports May 2018Salmonella is a major foodborne pathogen which successfully infects animal species for human consumption such as swine. The pathogen has a battery of virulence factors...
Salmonella is a major foodborne pathogen which successfully infects animal species for human consumption such as swine. The pathogen has a battery of virulence factors which it uses to colonise and persist within the host. The host microbiota may play a role in resistance to, and may also be indirectly responsible from some of the consequences of, Salmonella infection. To investigate this, we used 16S rRNA metagenomic sequencing to determine the changes in the gut microbiota of pigs in response to infection by Salmonella Typhimurium at three locations: ileum mucosa, ileum content and faeces. Early infection (2 days post-infection) impacted on the microbiome diversity at the mucosa, reflected in a decrease in representatives of the generally regarded as desirable genera (i.e., Bifidobacterium and Lactobacillus). Severe damage in the epithelium of the ileum mucosa correlated with an increase in synergistic (with respect to Salmonella infection; Akkermansia) or opportunistically pathogenic bacteria (Citrobacter) and a depletion in anaerobic bacteria (Clostridium spp., Ruminococcus, or Dialliser). Predictive functional analysis, together with metabolomic analysis revealed changes in glucose and lipid metabolism in infected pigs. The observed changes in commensal healthy microbiota, including the growth of synergistic or potentially pathogenic bacteria and depletion of beneficial or competing bacteria, could contribute to the pathogen's ability to colonize the gut successfully. The findings from this study could be used to form the basis for further research aimed at creating intervention strategies to mitigate the effects of Salmonella infection.
Topics: Animals; Feces; Ileum; Intestinal Mucosa; Microbiota; Salmonella Infections; Salmonella typhimurium; Swine
PubMed: 29773876
DOI: 10.1038/s41598-018-26083-3 -
European Journal of Cell Biology Dec 2023Salmonella enterica serovar Typhimurium manipulates cellular Rho GTPases for host cell invasion by effector protein translocation via the Type III Secretion System...
Salmonella enterica serovar Typhimurium manipulates cellular Rho GTPases for host cell invasion by effector protein translocation via the Type III Secretion System (T3SS). The two Guanine nucleotide exchange (GEF) mimicking factors SopE and -E2 and the inositol phosphate phosphatase (PiPase) SopB activate the Rho GTPases Rac1, Cdc42 and RhoA, thereby mediating bacterial invasion. S. Typhimurium lacking these three effector proteins are largely invasion-defective. Type III secretion is crucial for both early and later phases of the intracellular life of S. Typhimurium. Here we investigated whether and how the small GTPase RhoB, known to localize on endomembrane vesicles and at the invasion site of S. Typhimurium, contributes to bacterial invasion and to subsequent steps relevant for S. Typhimurium lifestyle. We show that RhoB is significantly upregulated within hours of Salmonella infection. This effect depends on the presence of the bacterial effector SopB, but does not require its phosphatase activity. Our data reveal that SopB and RhoB bind to each other, and that RhoB localizes on early phagosomes of intracellular S. Typhimurium. Whereas both SopB and RhoB promote intracellular survival of Salmonella, RhoB is specifically required for Salmonella-induced upregulation of autophagy. Finally, in the absence of RhoB, vacuolar escape and cytosolic hyper-replication of S. Typhimurium is diminished. Our findings thus uncover a role for RhoB in Salmonella-induced autophagy, which supports intracellular survival of the bacterium and is promoted through a positive feedback loop by the Salmonella effector SopB.
Topics: Humans; Salmonella Infections; Salmonella typhimurium; rho GTP-Binding Proteins; Autophagy; Phosphoric Monoester Hydrolases
PubMed: 37703749
DOI: 10.1016/j.ejcb.2023.151358 -
The American Journal of Case Reports Jun 2022BACKGROUND Rhabdomyolysis is a clinical syndrome characterized by elevated serum creatine kinase (CK) and myoglobin levels due to the breakdown of muscle fibers and is...
BACKGROUND Rhabdomyolysis is a clinical syndrome characterized by elevated serum creatine kinase (CK) and myoglobin levels due to the breakdown of muscle fibers and is associated with symptoms such as myalgia, muscle swelling, and erythruria. Rhabdomyolysis has an array of potential causes, including Salmonella infection, although rare. We report 2 cases in which nontyphoidal salmonellae caused acute gastroenteritis complicated by rhabdomyolysis and myoglobinuric acute kidney injury (AKI). CASE REPORT Two male patients, aged 69 years and 62 years, presented to our hospital with sudden-onset fever, abdominal pain, and watery diarrhea. At the time of admission, the patients had elevated serum CK levels (32 225 U/L and 10 590 U/L, respectively) and serum creatinine levels (4.8 mg/dL and 8.8 mg/dL, respectively). Both patients also had elevated serum myoglobin concentrations with significant myoglobinuria. They were administered fluid therapy and intravenous empirical antibiotics (cefotaxime and metronidazole for Case 1, ciprofloxacin for Case 2). The patient in Case 2 underwent 3 sessions of hemodialysis due to persistent oliguria and exacerbation of metabolic acidosis. Salmonella B (Case 1) and Salmonella C (Case 2) were isolated from blood cultures. After about 2 weeks of inpatient care, both patients showed improvement of clinical symptoms and were discharged. CONCLUSIONS Patients with acute gastroenteritis induced by Salmonella infection can develop rhabdomyolysis and myoglobinuric AKI in rare cases. Timely administration of appropriate antibiotics and fluids is expected to produce a favorable prognosis. Furthermore, early initiation of hemodialysis after onset of oliguric AKI can improve clinical outcomes.
Topics: Acute Kidney Injury; Anti-Bacterial Agents; Creatine Kinase; Gastroenteritis; Humans; Male; Myoglobin; Rhabdomyolysis; Salmonella Infections
PubMed: 35672938
DOI: 10.12659/AJCR.936407 -
Zhongguo Dang Dai Er Ke Za Zhi =... Nov 2018To study the clinical features and drug resistance in children with Salmonella infection.
OBJECTIVE
To study the clinical features and drug resistance in children with Salmonella infection.
METHODS
A total of 163 children with positive fecal cultures for Salmonella who were hospitalized between 2013 and 2017 were enrolled. A retrospective analysis was performed for their data on clinical features, distribution of Salmonella serotypes, and drug sensitivity test results.
RESULTS
Among the 163 children with Salmonella infection, 79 (48.5%) were aged ≤1 year. Main clinical manifestations included fever and diarrhea. Of all the children, 121 (74.2%) reached a body temperature of above 39°C, 52 (31.9%) had diarrhea more than 10 times a day, and 56 (34.4%) had respiratory infection. Salmonella infection often occurred in summer and autumn. Of all the children, 131 (80.4%) had the infection in May to October. Salmonella typhimurium was observed in 100 children (61.3%) and Salmonella enteritidis was observed 15 children (9.2%). All serotypes of Salmonella had a drug resistance rate of >20% to cefotaxime, as well as high sensitivities to β-lactamase inhibitors (amoxicillin/clavulanic acid and piperacillin/tazobactam). There were no strains resistant to carbapenems including imipenem.
CONCLUSIONS
Infants aged ≤1 year are susceptible to Salmonella infection in summer and autumn, and the most common serotype is Salmonella typhimurium. Main clinical manifestations are fever and diarrhea in children with Salmonella infection, and most children also have respiratory infection. Salmonella has an increased rate of drug resistance to third-generation cephalosporins. In clinical treatment, antimicrobial drugs should be used according to the results of drug sensitivity test.
Topics: Anti-Bacterial Agents; Child; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Retrospective Studies; Salmonella Infections
PubMed: 30477623
DOI: 10.7499/j.issn.1008-8830.2018.11.008 -
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 -
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 -
The Journal of Antimicrobial... Dec 2017We determined the interactions between efficacy of antibiotic treatment, pathogen growth rates and between-organ spread during systemic Salmonella infections.
OBJECTIVES
We determined the interactions between efficacy of antibiotic treatment, pathogen growth rates and between-organ spread during systemic Salmonella infections.
METHODS
We infected mice with isogenic molecularly tagged subpopulations of either a fast-growing WT or a slow-growing ΔaroC Salmonella strain. We monitored viable bacterial numbers and fluctuations in the proportions of each bacterial subpopulation in spleen, liver, blood and mesenteric lymph nodes (MLNs) before, during and after the cessation of treatment with ampicillin and ciprofloxacin.
RESULTS
Both antimicrobials induced a reduction in viable bacterial numbers in the spleen, liver and blood. This reduction was biphasic in infections with fast-growing bacteria, with a rapid initial reduction followed by a phase of lower effect. Conversely, a slow and gradual reduction of the bacterial load was seen in infections with the slow-growing strain, indicating a positive correlation between bacterial net growth rates and the efficacy of ampicillin and ciprofloxacin. The viable numbers of either bacterial strain remained constant in MLNs throughout the treatment with a relapse of the infection with WT bacteria occurring after cessation of the treatment. The frequency of each tagged bacterial subpopulation was similar in the spleen and liver, but different from that of the MLNs before, during and after treatment.
CONCLUSIONS
In Salmonella infections, bacterial growth rates correlate with treatment efficacy. MLNs are a site with a bacterial population structure different to those of the spleen and liver and where the total viable bacterial load remains largely unaffected by antimicrobials, but can resume growth after cessation of treatment.
Topics: Ampicillin; Animal Structures; Animals; Anti-Bacterial Agents; Bacterial Load; Blood; Ciprofloxacin; Disease Models, Animal; Female; Mice, Inbred C57BL; Salmonella; Salmonella Infections; Sepsis; Spatio-Temporal Analysis
PubMed: 28962012
DOI: 10.1093/jac/dkx294 -
Infection and Immunity Oct 2016Salmonella infection profoundly affects host erythroid development, but the mechanisms responsible for this effect remain poorly understood. We monitored the impact of...
Salmonella infection profoundly affects host erythroid development, but the mechanisms responsible for this effect remain poorly understood. We monitored the impact of Salmonella infection on erythroid development and found that systemic infection induced anemia, splenomegaly, elevated erythropoietin (EPO) levels, and extramedullary erythropoiesis in a process independent of Salmonella pathogenicity island 2 (SPI2) or flagellin. The circulating EPO level was also constitutively higher in mice lacking the expression of signal-regulatory protein α (SIRPα). The expression level of EPO mRNA was elevated in the kidney and liver but not increased in the spleens of infected mice despite the presence of extramedullary erythropoiesis in this tissue. In contrast to data from a previous report, mice lacking EPO receptor (EPOR) expression on nonerythroid cells (EPOR rescued) had bacterial loads similar to those of wild-type mice following Salmonella infection. Indeed, treatment to reduce splenic erythroblasts and mature red blood cells correlated with elevated bacterial burdens, implying that extramedullary erythropoiesis benefits the host. Together, these findings emphasize the profound effect of Salmonella infection on erythroid development and suggest that the modulation of erythroid development has both positive and negative consequences for host immunity.
Topics: Anemia; Animals; Bacterial Load; Disease Models, Animal; Erythropoiesis; Erythropoietin; Flow Cytometry; Kidney; Liver; Mice; Mice, Inbred C57BL; RNA, Messenger; Receptors, Erythropoietin; Receptors, Immunologic; Salmonella Infections; Salmonella typhi; Spleen
PubMed: 27456828
DOI: 10.1128/IAI.00337-16 -
Epidemiology and Infection Dec 2017We conducted a hospital-based cross-sectional study among children aged <5 years in Thi-Qar Governorate, south-eastern Iraq, in order to examine the prevalence, risk...
We conducted a hospital-based cross-sectional study among children aged <5 years in Thi-Qar Governorate, south-eastern Iraq, in order to examine the prevalence, risk factors and antimicrobial resistance associated with gastroenteritis caused by Salmonella infection. From 320 diarrhoea cases enrolled between March and August 2016, 33 (10·3%, 95% confidence interval (CI) 8·4-12·4) cases were stool culture-positive for non-typhoidal Salmonella enterica. The most commonly identified serovar was Typhimurium (54%). Multivariable logistic regression analysis indicated that the odds of Salmonella infection in children from households supplied by pipe water was 4·7 (95% CI 1·6-13·9) times higher compared with those supplied with reverse osmosis treated water. Similarly, children from households with domestic animals were found to have a higher odds (OR 10·5; 95% CI 3·8-28·4) of being Salmonella stool culture-positive. The likelihood of Salmonella infection was higher (OR 3·9; 95% CI 1·0-6·4) among children belonging to caregiver with primary vs. tertiary education levels. Lower odds (OR 0·4; 95% CI 0·1-0·9) of Salmonella infection were associated with children exclusively breast fed as compared with those exclusively bottle fed. Salmonella infection was three times lower (95% CI 0·1-0·7) in children belonging to caregiver who reported always washing hands after cleaning children following defecation, vs. those belonging to caregivers who did not wash hands. The antimicrobial resistance profile by disc diffusion revealed that non-susceptibility to tetracycline (78·8%), azithromycin (66·7%) and ciprofloxacin (57·6%) were the most commonly seen, and 84·9% of Salmonella isolates were classified as multi-drug resistant. This is the first study on prevalence and antimicrobial resistance of Salmonella infection among children in this setting. This work provides specific epidemiological data which are crucial to understand and combat paediatric diarrhoea in Iraq.
Topics: Anti-Bacterial Agents; Child, Preschool; Cross-Sectional Studies; Diarrhea; Drug Resistance, Bacterial; Feces; Female; Humans; Infant; Infant, Newborn; Iraq; Male; Prevalence; Risk Factors; Salmonella; Salmonella Infections
PubMed: 29103396
DOI: 10.1017/S0950268817002400 -
Scientific Reports Jan 2021Nontyphoidal salmonella (NTS) infection has a high mortality rate. Bowel resections affect gut microbiota and immune function, and the association between bowel...
Nontyphoidal salmonella (NTS) infection has a high mortality rate. Bowel resections affect gut microbiota and immune function, and the association between bowel resection and NTS infection in human beings has not been addressed. We conducted a nationwide propensity score (PS)-matched cohort study to clarify this association. Data from the Longitudinal Health Insurance Database of Taiwan were used to establish a case-cohort with bowel resections from 2000 to 2013. Informed consent was waived by the Institutional Review Board of China Medical University Hospital (CMUH104-REC2-115) because all personal identifying information used had been de-identified. Each case was matched with one control without any bowel resection according to age, gender, index date, and propensity score (PS). Cumulative incidences of and hazard ratios (HRs) for NTS infection development were analyzed. The incidence of NTS infection was greater in patients with a bowel resection than in the control group (2.97 vs. 1.92 per 10,000 person-years), with an adjusted hazard ratio (aHR) of 1.64 (95% CI = 1.08-2.48). The incidence of NTS infection increased significantly for cases with small bowel resections and right hemicolectomies. Age (31-40 and > 50 years), hypertension, chronic kidney disease, chronic obstructive pulmonary disease, and autoimmune diseases were significant risk factors of NTS infection. Stratification analysis revealed that patients without comorbidities were prone to NTS infection after bowel resections. The increased risk of developing NTS infection could be related to the bowel resection. Specific age groups and comorbidities also contribute to increased risk of NTS infection.
Topics: Adolescent; Adult; Databases, Factual; Digestive System Surgical Procedures; Female; Humans; Incidence; Intestine, Small; Male; Middle Aged; Postoperative Complications; Salmonella Infections; Taiwan
PubMed: 33446836
DOI: 10.1038/s41598-021-81224-5