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Proceedings of the National Academy of... Jun 2024causes life-threatening wound and gastrointestinal infections, mediated primarily by the production of a Multifunctional-Autoprocessing Repeats-In-Toxin (MARTX) toxin....
causes life-threatening wound and gastrointestinal infections, mediated primarily by the production of a Multifunctional-Autoprocessing Repeats-In-Toxin (MARTX) toxin. The most commonly present MARTX effector domain, the Makes Caterpillars Floppy-like (MCF) toxin, is a cysteine protease stimulated by host adenosine diphosphate (ADP) ribosylation factors (ARFs) to autoprocess. Here, we show processed MCF then binds and cleaves host s-related proteins in rain (Rab) guanosine triphosphatases within their C-terminal tails resulting in Rab degradation. We demonstrate MCF binds Rabs at the same interface occupied by ARFs. Moreover, we show MCF preferentially binds to ARF1 prior to autoprocessing and is active to cleave Rabs only subsequent to autoprocessing. We then use structure prediction algorithms to demonstrate that structural composition, rather than sequence, determines Rab target specificity. We further determine a crystal structure of aMCF as a swapped dimer, revealing an alternative conformation we suggest represents the open, activated state of MCF with reorganized active site residues. The cleavage of Rabs results in Rab1B dispersal within cells and loss of Rab1B density in the intestinal tissue of infected mice. Collectively, our work describes an extracellular bacterial mechanism whereby MCF is activated by ARFs and subsequently induces the degradation of another small host guanosine triphosphatase (GTPase), Rabs, to drive organelle damage, cell death, and promote pathogenesis of these rapidly fatal infections.
Topics: Animals; Female; Humans; Mice; ADP-Ribosylation Factors; Bacterial Toxins; HEK293 Cells; Mice, Inbred ICR; Proteolysis; rab GTP-Binding Proteins; Vibrio Infections; Vibrio vulnificus
PubMed: 38861595
DOI: 10.1073/pnas.2316143121 -
Microbiology Spectrum Jul 2024The incidence of infections, with high mortality rates in humans and aquatic animals, has escalated, highlighting a significant public health challenge. Currently,...
The incidence of infections, with high mortality rates in humans and aquatic animals, has escalated, highlighting a significant public health challenge. Currently, reliable markers to identify strains with high virulence potential are lacking, and the understanding of evolutionary drivers behind the emergence of pathogenic strains is limited. In this study, we analyzed the distribution of virulent genotypes and phenotypes to discern the infectious potential of strains isolated from three distinct sources. Most isolates, traditionally classified as biotype 1, possessed the virulence-correlated gene-C type. Environmental isolates predominantly exhibited YJ-like alleles, while clinical and diseased fish isolates were significantly associated with the gene and pathogenicity region XII. Hemolytic activity was primarily observed in the culture supernatants of clinical and diseased fish isolates. Genetic relationships, as determined by multiple-locus variable-number tandem repeat analysis, suggested that strains originating from the same source tended to cluster together. However, multilocus sequence typing revealed considerable genetic diversity across clusters and sources. A phylogenetic analysis using single nucleotide polymorphisms of diseased fish strains alongside publicly available genomes demonstrated a high degree of evolutionary relatedness within and across different isolation sources. Notably, our findings reveal no direct correlation between phylogenetic patterns, isolation sources, and virulence capabilities. This underscores the necessity for proactive risk management strategies to address pathogenic strains emerging from environmental reservoirs.IMPORTANCEAs the global incidence of infections rises, impacting human health and marine aquacultures, understanding the pathogenicity of environmental strains remains critical yet underexplored. This study addresses this gap by evaluating the virulence potential and genetic relatedness of strains, focusing on environmental origins. We conduct an extensive genotypic analysis and phenotypic assessment, including virulence testing in a wax moth model. Our findings aim to uncover genetic and evolutionary factors that drive pathogenic strain emergence in the environment. This research advances our ability to identify reliable virulence markers and understand the distribution of pathogenic strains, offering significant insights for public health and environmental risk management.
Topics: Vibrio vulnificus; Animals; Vibrio Infections; Humans; Phylogeny; Virulence; Genetic Variation; Fish Diseases; Fishes; Multilocus Sequence Typing; Virulence Factors; Genotype; Genome, Bacterial
PubMed: 38860819
DOI: 10.1128/spectrum.00079-24 -
Frontiers in Public Health 2024In Ethiopia, despite major improvements seen in health service delivery system, the country continues to be significantly affected by cholera outbreaks. Cholera remains...
INTRODUCTION
In Ethiopia, despite major improvements seen in health service delivery system, the country continues to be significantly affected by cholera outbreaks. Cholera remains a significant public health problem among the vulnerable populations living in many resource-limited settings with poor access to safe and clean water and hygiene practices. Recurring cholera outbreaks are an indication of deprived water and sanitation conditions as well as weak health systems, contributing to the transmission and spread of the cholera infection.
OBJECTIVE
To assess the cholera outbreak, its challenges, and the way forward on public health interventions to solve the knowledge and health service delivery gaps related to cholera control in Guraghe Zone, Ethiopia, 2023.
METHODS
Active surveillance of the cholera outbreak was conducted in all kebeles and town administrative of Guraghe zone from 7/8/2023 to 30/10/2023. A total of 224 cholera cases were detected during the active surveillance method. Data obtained from Guraghe zone offices were exported to SPSS version 25 for additional analysis. The case fatality rate, incidence of the cases, and other descriptive variables were presented and described using figures and tables.
RESULT
A total of 224 cholera cases were detected through an active surveillance system. In this study, the case fatality rate of cholera outbreak was 2.6%. To tackle the cholera outbreak, the Guraghe zone health office collaborated with other stakeholders to prepare four cholera treatment centers. The absence of OCV, inaccessible safe water, low latrine coverage, inappropriate utilization of latrines, and absence of cholera laboratory rapid diagnostics test in Guraghe Zone are barriers to tackling the outbreak.
CONCLUSION
Ethiopia National Cholera Plan targeted eradicating cholera by 2030, 222 cholera outbreak occurred in Guraghe Zone, Ethiopia. To minimize and control cholera mortality rate oral cholera vaccinations should be employed in all areas of the region. Sustainable WASH measures should be guaranteed for the use of safe water and good hygiene practices. Early diagnosis and treatment should be initiated appropriately for those who are infected.
Topics: Cholera; Ethiopia; Humans; Disease Outbreaks; Adolescent; Female; Male; Sanitation; Public Health; Adult; Child; Middle Aged; Young Adult; Child, Preschool; Incidence
PubMed: 38859897
DOI: 10.3389/fpubh.2024.1355613 -
The Science of the Total Environment Sep 2024The final point-of-drinking water (FPODW) exposure to Vibrio and waterborne pathogens remains a misaim surveillance target. Therefore, the current study purposed to... (Meta-Analysis)
Meta-Analysis
Global and regional final point-of-drinking water prevalence of Vibrio pathogens: a systematic analysis with socioeconomic, global health security, and WASH indices-guided meta-regressions.
The final point-of-drinking water (FPODW) exposure to Vibrio and waterborne pathogens remains a misaim surveillance target. Therefore, the current study purposed to estimate the global and regional prevalence of Vibrio pathogens in FPODW. Vibrio-FPODW data derived from integrated databases per PRISMA protocol were fitted to a random-intercept-logistic mixed-effects and meta-regression models. The global FPODW Vibrio prevalence was 5.13% (95%CI: 2.24-11.30) with 7.76% (6.84-8.78) cross-validated value. Vibrio prevalence in different FPODW varied with the highest in unclassified (13.98%, 3.98-38.95), household stored (6.42%, 1.16-28.69), municipal (4.39%, 1.54-11.90), and bottled (1.06%, 0.00-98.57) FPODW. Regionally, FPODW Vibrio prevalence varied significantly with highest in Africa (6.31%, 0.49-47.88), then Asia (4.83%, 2.01-11.18). Similarly, it varied significantly among income classification with the highest from low-income (8.77%, 0.91-50.05), then lower-middle-income (6.16%, 2.75-13.20), upper-middle-income (0.23%, 0.00-82.04), and 0.94% (0.19-2.72) in high-income economies. Among the WHO region, it varied significantly from 1.41% (0.17-10.45) in Eastern Mediterranean, 6.31% (0.49-47.88) in Africa to 8.86% (3.85-19.06) in South-East Asia and declining among SDI-quintiles from 11.64% (3.29-33.83) in Low-SDI, 10.59% (4.58-22.61) in High-middle-SDI to 0.26% (0.01-9.09) in Middle-SDI. FPODW Vibrio prevalence was 7.31% (2.94-17.03) in the low-GHSIG, followed by 4.55% (0.00-100.00) in the upper-GHSIG, and 2.21% (0.31-14.24) in middle-GHSIG; rural (4.18%, 0.06-76.17) and urban (5.28%, 2.35-11.44) settings. Also, sample size, SDI, SDI-quintiles, and nation significantly explained 14.12%, 10.91%, 30.35%, and 87.65% variance in FPODW Vibrio prevalence, respectively as a univariate influence. Additionally, 11.90% variance in FPODW Vibrio prevalence explained mortality rate attributed to unsafe WASH services. In conclusion, the study revealed a substantial high FPODW prevalence of Vibrio calling for initiative-taking and intentional surveillances of waterborne pathogens at the neglected stage across nations in order to achieve sustainably the SDG 3.
Topics: Vibrio; Drinking Water; Prevalence; Water Microbiology; Global Health; Humans; Socioeconomic Factors
PubMed: 38852862
DOI: 10.1016/j.scitotenv.2024.173818 -
Southern African Journal of Infectious... 2024Cholera, a severe diarrhoeal disease caused by is typically associated with inadequate potable water supply and poor sanitation. We report cholera disease presentation...
UNLABELLED
Cholera, a severe diarrhoeal disease caused by is typically associated with inadequate potable water supply and poor sanitation. We report cholera disease presentation identified as a suspected case of acute diarrhoea (HIV/AIDS common condition) in a person living with HIV seen in a cholera non-endemic area.
CONTRIBUTION
We highlight the importance of recognizing cholera in cases of acute diarrhoea, especially among people with HIV, in resource-constraint areas that lack potable water supply.
PubMed: 38841342
DOI: 10.4102/sajid.v39i1.619 -
Asian Journal of Surgery Jun 2024
PubMed: 38839495
DOI: 10.1016/j.asjsur.2024.05.177 -
Food Microbiology Sep 2024Acanthamoeba spp., are ubiquitous protist which belongs to Free-Living Amoeba (FLA) group, is considered as causal agent of side-threatening keratitis or fatal...
Acanthamoeba spp., are ubiquitous protist which belongs to Free-Living Amoeba (FLA) group, is considered as causal agent of side-threatening keratitis or fatal encephalitis among other human infections. Besides, this parasite has been reported as host for other microorganisms important to human health such as Campylobacter spp. or Vibrio spp. among others. This role of Acanthamoeba as pathogen and environmental phagocyte has increased the reports confirming its presence in human related environments, acting as a water quality indicator. Considering the tide relationship between water and kitchen environments, and the high prevalence of Acanthamoeba in water sources, the present study aims to establish a quick and accurate protocol based on DNA extraction and a real time qPCR assay to detect Acanthamoeba spp. in dishcloths. The procedure has been validated by processing 17 used dishcloths. Our findings demonstrated the high sensitivity of the qPCR assay used which was capable of detecting up to one Acanthamoeba from an in vitro contaminated dishcloth. The protocol accurately detected 64.7% of positive samples for Acanthamoeba spp, (in 4 samples DNA concentrations corresponded to 1-10 amoebae). Our findings demonstrate the importance of FLA surveillance by efficient and sensitive methods since one amoeba is capable of colonizing human related food environments such as kitchens sinks and could be a potential source of infection.
Topics: Acanthamoeba; Real-Time Polymerase Chain Reaction; DNA, Protozoan; Humans; Sensitivity and Specificity
PubMed: 38839225
DOI: 10.1016/j.fm.2024.104562 -
Fish & Shellfish Immunology Jun 2024MicroRNAs (miRNAs) play a fundamental role in the post-transcriptional regulation of genes and are pivotal in modulating immune responses in marine species, particularly...
MicroRNAs (miRNAs) play a fundamental role in the post-transcriptional regulation of genes and are pivotal in modulating immune responses in marine species, particularly during pathogen assaults. This study focused on the function of miR-7562 and its regulatory effects on autophagy against Vibrio harveyi infection in the black tiger shrimp (Penaeus monodon), an economically important aquatic species. We successfully cloned and characterized two essential autophagy-related genes (ATGs) from P. monodon, PmATG5 and PmATG12, and then identified the miRNAs potentially involved in co-regulating these genes, which were notably miR-7562, miR-8485, and miR-278. Subsequent bacterial challenge experiments and dual-luciferase reporter assays identified miR-7562 as the principal regulator of both genes, particularly by targeting the 3'UTR of each gene. By manipulating the in vivo levels of miR-7562 using mimics and antagomirs, we found significant differences in the expression of PmATG5 and PmATG12, which corresponded to alterations in autophagic activity. Notably, miR-7562 overexpression resulted in the downregulation of PmATG5 and PmATG12, leading to a subdued autophagic response. Conversely, miR-7562 knockdown elevated the expression levels of these genes, thereby enhancing autophagic activity. Our findings further revealed that during V. harveyi infection, miR-7562 continued to influence the autophagic pathway by specifically targeting the ATG5-ATG12 complex. This research not only sheds light on the miRNA-dependent mechanisms governing autophagic immunity in shrimp but also proposes miR-7562 as a promising target for therapeutic strategies intended to strengthen disease resistance within the crustacean aquaculture industry.
PubMed: 38838838
DOI: 10.1016/j.fsi.2024.109670 -
Diagnostic Microbiology and Infectious... Jun 2024Vibrio cholerae non-O1/non-O139 (NOVC) bacteremia is infrequently reported in Western countries and is associated with unfavorable outcome.
OBJECTIVES
Vibrio cholerae non-O1/non-O139 (NOVC) bacteremia is infrequently reported in Western countries and is associated with unfavorable outcome.
PATIENT/METHOD
We describe here the case of a diabetic patient with hepatic cytolysis and NOVC bacteremia following an episode of diarrhea.
RESULT
The patient was paucisymptomatic and had a favorable resolution with oral ciprofloxacin.
CONCLUSION
NOVC should be systematically sought in stool samples, particularly in immunocompromised patients, due to an increased risk of infection occurrence.
PubMed: 38838459
DOI: 10.1016/j.diagmicrobio.2024.116371 -
Microbiology Spectrum Jul 2024is a threat to human health and one of the leading bacterial causes of seafood-borne infection worldwide. This pathogen is autochtonous in the marine environment and is...
is a threat to human health and one of the leading bacterial causes of seafood-borne infection worldwide. This pathogen is autochtonous in the marine environment and is able to acquire antimicrobial resistance (AMR) mechanisms, which is a global concern. However, the emergence of AMR strains in seafood is still understudied, as interpretation criteria for this species for antimicrobial susceptibility tests are limited in the literature. In this study, we investigated the susceptibility profiles to clinically important antibiotics and the associated genetic determinants of isolates cultured from imported shrimps. Based on the analysis of the resistance phenotypes of 304 . isolates, we have defined experimental epidemiological cutoff values (CO) for 14/15 antibiotics tested. We observed that 19.1% of the bacterial isolates had acquired resistance to at least one antibiotic class. The highest number of resistance was associated with tetracycline (14.5% of the strains) and trimethoprim-sulfamethoxazole (3.6%). Moreover, seven strains were multidrug-resistant (MDR, resistant to at least three antibiotic classes). The most frequently identified genes in these strains were / (aminoglycoside resistance), (sulfonamide), ) (tetracycline), and (chloramphenicol). The SXT/R391 family ICE and class 1 integron-integrase genes were detected by PCR in three and one MDR strains, respectively. Consequently, in seafood can act as a reservoir of AMR, constituting a health risk for the consumer.IMPORTANCEOur study on "Antimicrobial Resistance Profiles and Genetic Determinants of Isolates from Imported Shrimps" addresses a critical gap in understanding the emergence of antimicrobial resistance (AMR) in this seafood-associated pathogen. is a major cause of global seafood-borne infections, and our research reveals that 19.1% of isolates from imported shrimps display resistance to at least one antibiotic class, with multidrug resistance observed in seven strains. Importantly, we establish experimental epidemiological cutoff values for antibiotic susceptibility, providing valuable criteria specific to . Our findings underscore the potential risk to consumers, emphasizing the need for vigilant monitoring and intervention strategies. This study significantly contributes to the comprehension of AMR dynamics in , offering crucial insights for global public health. The dissemination of our research through Microbiology Spectrum ensures broad accessibility and impact within the scientific community and beyond.
Topics: Vibrio parahaemolyticus; Animals; Anti-Bacterial Agents; Microbial Sensitivity Tests; Seafood; Drug Resistance, Multiple, Bacterial; Vibrio Infections; Penaeidae; Humans; Drug Resistance, Bacterial
PubMed: 38832768
DOI: 10.1128/spectrum.00175-24