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BioRxiv : the Preprint Server For... May 2024Bacteria and phages are locked in a co-evolutionary arms race where each entity evolves mechanisms to restrict the proliferation of the other. Phage-encoded defense...
UNLABELLED
Bacteria and phages are locked in a co-evolutionary arms race where each entity evolves mechanisms to restrict the proliferation of the other. Phage-encoded defense inhibitors have proven powerful tools to interrogate how defense systems function. A relatively common defense system is BREX (Bacteriophage exclusion); however, how BREX functions to restrict phage infection remains poorly understood. A BREX system encoded by the SXT integrative and conjugative element, Ind5, was recently identified in , the causative agent of the diarrheal disease cholera. The lytic phage ICP1 that co-circulates with encodes the BREX inhibitor OrbA, but how OrbA inhibits BREX is unclear. Here, we determine that OrbA inhibits BREX using a unique mechanism from known BREX inhibitors by directly binding to the BREX component BrxC. BrxC has a functional ATPase domain that, when mutated, not only disrupts BrxC function but also alters how BrxC multimerizes. Furthermore, we find that OrbA binding disrupts BrxC-BrxC interactions. We determine that OrbA cannot bind BrxC encoded by the distantly related BREX system encoded by the SXT Ban9, and thus fails to inhibit this BREX system that also circulates in epidemic . Lastly, we find that homologs of the Ind5 BrxC are more diverse than the homologs of the Ban9 BrxC. These data provide new insight into the function of the BrxC ATPase and highlight how phage-encoded inhibitors can disrupt phage defense systems using different mechanisms.
IMPORTANCE
With renewed interest in phage therapy to combat antibiotic-resistant pathogens, understanding the mechanisms bacteria use to defend themselves against phages and the counter-strategies phages evolve to inhibit defenses is paramount. Bacteriophage exclusion (BREX) is a common defense system with few known inhibitors. Here, we probe how the vibriophage-encoded inhibitor OrbA inhibits the BREX system of , the causative agent of the diarrheal disease cholera. By interrogating OrbA function, we have begun to understand the importance and function of a BREX component. Our results demonstrate the importance of identifying inhibitors against defense systems, as they are powerful tools for dissecting defense activity and can inform strategies to increase the efficacy of some phage therapies.
PubMed: 38766029
DOI: 10.1101/2024.05.09.593382 -
Scientific Reports May 2024To study the dynamical system, it is necessary to formulate the mathematical model to understand the dynamics of various diseases which are spread in the world wide. The...
To study the dynamical system, it is necessary to formulate the mathematical model to understand the dynamics of various diseases which are spread in the world wide. The objective of the research study is to assess the early diagnosis and treatment of cholera virus by implementing remedial methods with and without the use of drugs. A mathematical model is built with the hypothesis of strengthening the immune system, and a ABC operator is employed to turn the model into a fractional-order model. A newly developed system SEIBR, which is examined both qualitatively and quantitatively to determine its stable position as well as the verification of flip bifurcation has been made for developed system. The local stability of this model has been explored concerning limited observations, a fundamental aspect of epidemic models. We have derived the reproductive number using next generation method, denoted as " ", to analyze its impact rate across various sub-compartments, which serves as a critical determinant of its community-wide transmission rate. The sensitivity analysis has been verified according to its each parameters to identify that how much rate of change of parameters are sensitive. Atangana-Toufik scheme is employed to find the solution for the developed system using different fractional values which is advanced tool for reliable bounded solution. Also the error analysis has been made for developed scheme. Simulations have been made to see the real behavior and effects of cholera disease with early detection and treatment by implementing remedial methods without the use of drugs in the community. Also identify the real situation the spread of cholera disease after implementing remedial methods with and without the use of drugs. Such type of investigation will be useful to investigate the spread of virus as well as helpful in developing control strategies from our justified outcomes.
Topics: Cholera; Humans; Models, Theoretical; Epidemics; Computer Simulation
PubMed: 38740856
DOI: 10.1038/s41598-024-59640-0 -
Case Reports in Infectious Diseases 2024Over 200 different serogroups of based on O-polysaccharide specificity have been described worldwide, including the two most important serogroups, O1 and O139....
Over 200 different serogroups of based on O-polysaccharide specificity have been described worldwide, including the two most important serogroups, O1 and O139. Non-O1/non-O139 serogroups generally do not produce the cholera-causing toxin but do sporadically cause gastroenteritis and extra-intestinal infections. Recently, however, bloodstream infections caused by non-O1/non-O139 are being increasingly reported, and these infections are associated with high mortality in immunocompromised hosts. We describe a case of non-O1/non-O139 bacteremia in a patient with autoimmune pancreatitis and stenosis of the intra- and extrahepatic bile ducts. The clinical manifestations of bacteremia were fever and mild digestive symptoms. The blood cultures showed , which was identified as a non-O1, non-O139 serogroup by slide agglutination tests and PCR. The bloodstream infection of the patient was likely caused by the consumption of contaminated seafood at a banquet. The patient recovered after the administration of a third-generation cephalosporin. Non-O1/non-O139 infection presents with or without gastrointestinal manifestations; close attention should be paid to the possibility of disseminated non-O1/non-O139 infection in high-risk patients.
PubMed: 38737750
DOI: 10.1155/2024/7219952 -
The Journal of Medical Investigation :... 2024Vibrio vulnificus (V. vulnificus) is a halophilic gram-negative bacterium that inhabits coastal warm water and induce severe diseases such as primary septicemia. To...
Vibrio vulnificus (V. vulnificus) is a halophilic gram-negative bacterium that inhabits coastal warm water and induce severe diseases such as primary septicemia. To investigate the mechanisms of rapid bacterial translocation on intestinal infection, we focused on outer membrane vesicles (OMVs), which are extracellular vesicles produced by Gram-negative bacteria and deliver virulence factors. However, there are very few studies on the pathogenicity or contents of V. vulnificus OMVs (Vv-OMVs). In this study, we investigated the effects of Vv-OMVs on host cells. Epithelial cells INT407 were stimulated with purified OMVs and morphological alterations and levels of lactate dehydrogenase (LDH) release were observed. In cells treated with OMVs, cell detachment without LDH release was observed, which exhibited different characteristics from cytotoxic cell detachment observed in V. vulnificus infection. Interestingly, OMVs from a Vibrio Vulnificus Hemolysin (VVH) and Multifunctional-autoprocessing repeats-in -toxin (MARTX) double-deletion mutant strain also caused cell detachment without LDH release. Our results suggested that the proteolytic function of a serine protease contained in Vv-OMVs may contribute to pathogenicity of V. vulnificus by assisting bacterial translocation. This study reveals a new pathogenic mechanism during V. vulnificus infections. J. Med. Invest. 71 : 102-112, February, 2024.
Topics: Vibrio vulnificus; Humans; Extracellular Vesicles; Hemolysin Proteins; L-Lactate Dehydrogenase; Bacterial Outer Membrane; Epithelial Cells
PubMed: 38735705
DOI: 10.2152/jmi.71.102 -
Microbiological Research Aug 2024Vibrio parahaemolyticus is the leading bacterial cause of gastroenteritis associated with seafood consumption worldwide. Not all members of the species are thought to be...
Vibrio parahaemolyticus is the leading bacterial cause of gastroenteritis associated with seafood consumption worldwide. Not all members of the species are thought to be pathogenic, thus identification of virulent organisms is essential to protect public health and the seafood industry. Correlations of human disease and known genetic markers (e.g. thermostable direct hemolysin (TDH), TDH-related hemolysin (TRH)) appear complex. Some isolates recovered from patients lack these factors, while their presence has become increasingly noted in isolates recovered from the environment. Here, we used whole-genome sequencing in combination with mammalian and insect models of infection to assess the pathogenic potential of V. parahaemolyticus isolated from European Atlantic shellfish production areas. We found environmental V. parahaemolyticus isolates harboured multiple virulence-associated genes, including TDH and/or TRH. However, carriage of these factors did not necessarily reflect virulence in the mammalian intestine, as an isolate containing TDH and the genes coding for a type 3 secretion system (T3SS) 2α virulence determinant, appeared avirulent. Moreover, environmental V. parahaemolyticus lacking TDH or TRH could be assigned to groups causing low and high levels of mortality in insect larvae, with experiments using defined bacterial mutants showing that a functional T3SS1 contributed to larval death. When taken together, our findings highlight the genetic diversity of V. parahaemolyticus isolates found in the environment, their potential to cause disease and the need for a more systematic evaluation of virulence in diverse V. parahaemolyticus to allow better genetic markers.
Topics: Vibrio parahaemolyticus; Animals; Virulence; Europe; Hemolysin Proteins; Virulence Factors; Vibrio Infections; Bacterial Proteins; Bacterial Toxins; Humans; Whole Genome Sequencing; Phenotype; Shellfish; Larva; Type III Secretion Systems; Genome, Bacterial; Seafood
PubMed: 38735242
DOI: 10.1016/j.micres.2024.127744 -
PLoS Medicine May 2024Cholera outbreaks are on the rise globally, with conflict-affected settings particularly at risk. Case-area targeted interventions (CATIs), a strategy whereby teams... (Observational Study)
Observational Study
BACKGROUND
Cholera outbreaks are on the rise globally, with conflict-affected settings particularly at risk. Case-area targeted interventions (CATIs), a strategy whereby teams provide a package of interventions to case and neighboring households within a predefined "ring," are increasingly employed in cholera responses. However, evidence on their ability to attenuate incidence is limited.
METHODS AND FINDINGS
We conducted a prospective observational cohort study in 3 conflict-affected states in Nigeria in 2021. Enumerators within rapid response teams observed CATI implementation during a cholera outbreak and collected data on household demographics; existing water, sanitation, and hygiene (WASH) infrastructure; and CATI interventions. Descriptive statistics showed that CATIs were delivered to 46,864 case and neighbor households, with 80.0% of cases and 33.5% of neighbors receiving all intended supplies and activities, in a context with operational challenges of population density, supply stock outs, and security constraints. We then applied prospective Poisson space-time scan statistics (STSS) across 3 models for each state: (1) an unadjusted model with case and population data; (2) an environmentally adjusted model adjusting for distance to cholera treatment centers and existing WASH infrastructure (improved water source, improved latrine, and handwashing station); and (3) a fully adjusted model adjusting for environmental and CATI variables (supply of Aquatabs and soap, hygiene promotion, bedding and latrine disinfection activities, ring coverage, and response timeliness). We ran the STSS each day of our study period to evaluate the space-time dynamics of the cholera outbreaks. Compared to the unadjusted model, significant cholera clustering was attenuated in the environmentally adjusted model (from 572 to 18 clusters) but there was still risk of cholera transmission. Two states still yielded significant clusters (range 8-10 total clusters, relative risk of 2.2-5.5, 16.6-19.9 day duration, including 11.1-56.8 cholera cases). Cholera clustering was completely attenuated in the fully adjusted model, with no significant anomalous clusters across time and space. Associated measures including quantity, relative risk, significance, likelihood of recurrence, size, and duration of clusters reinforced the results. Key limitations include selection bias, remote data monitoring, and the lack of a control group.
CONCLUSIONS
CATIs were associated with significant reductions in cholera clustering in Northeast Nigeria despite operational challenges. Our results provide a strong justification for rapid implementation and scale-up CATIs in cholera-response, particularly in conflict settings where WASH access is often limited.
Topics: Humans; Nigeria; Cholera; Prospective Studies; Sanitation; Male; Hygiene; Female; Adult; Epidemics; Incidence; Disease Outbreaks; Adolescent; Young Adult; Middle Aged; Child
PubMed: 38728366
DOI: 10.1371/journal.pmed.1004404 -
Pathogens and Disease Feb 2024The development of sustainable alternatives to conventional antimicrobials is needed to address bacterial virulence while avoiding selecting resistant strains in a...
The development of sustainable alternatives to conventional antimicrobials is needed to address bacterial virulence while avoiding selecting resistant strains in a variety of fields, including human, animal, and plant health. Quorum sensing (QS), a bacterial communication system involved in noxious bacterial phenotypes such as virulence, motility, and biofilm formation, is of utmost interest. In this study, we harnessed the potential of the lactonase SsoPox to disrupt QS of human, fish, and plant pathogens. Lactonase treatment significantly alters phenotypes including biofilm formation, motility, and infection capacity. In plant pathogens, SsoPox decreased the production of plant cell wall degrading enzymes in Pectobacterium carotovorum and reduced the maceration of onions infected by Burkholderia glumae. In human pathogens, lactonase treatment significantly reduced biofilm formation in Acinetobacter baumannii, Burkholderia cepacia, and Pseudomonas aeruginosa, with the cytotoxicity of the latter being reduced by SsoPox treatment. In fish pathogens, lactonase treatment inhibited biofilm formation and bioluminescence in Vibrio harveyi and affected QS regulation in Aeromonas salmonicida. QS inhibition can thus be used to largely impact the virulence of bacterial pathogens and would constitute a global and sustainable approach for public, crop, and livestock health in line with the expectations of the One Health initiative.
Topics: Quorum Sensing; Animals; Humans; Virulence; Biofilms; Bacteria; Plant Diseases; Anti-Bacterial Agents
PubMed: 38724459
DOI: 10.1093/femspd/ftae009 -
Frontiers in Immunology 2024Vibriosis, caused by , seriously affects the health of fish, shellfish, and shrimps, causing large economic losses. Teleosts are represent the first bony vertebrates...
Vibriosis, caused by , seriously affects the health of fish, shellfish, and shrimps, causing large economic losses. Teleosts are represent the first bony vertebrates with both innate and adaptive immune responses against pathogens. Aquatic animals encounter hydraulic pressure and more pathogens, compared to terrestrial animals. The skin is the first line of defense in fish, constituting the skin-associated lymphoid tissue (SALT), which belongs to the main mucosa-associated lymphoid tissues (MALT). However, little is known about the function of immunity related proteins in fish. Therefore, this study used iTRAQ (isobaric tags for relative and absolute quantitation) to compare the skin proteome between the resistant and susceptible families of . The protein integrin beta-2, the alpha-enolase isoform X1, subunit B of V-type proton ATPase, eukaryotic translation initiation factor 6, and ubiquitin-like protein ISG15, were highly expressed in the resistant family. The 16S sequencing of the skin tissues of the resistant and susceptible families showed significant differences in the microbial communities of the two families. The protein-microbial interaction identified ten proteins associated with skin microbes, including immunoglobulin heavy chain gene (IGH), B-cell lymphoma/leukemia 10 (BCL10) and pre-B-cell leukemia transcription factor 1 isoform X2 (PBX2). This study highlights the interaction between skin proteins and the microbial compositions of and provides new insights into understanding aquaculture breeding research.
Topics: Animals; Skin; Fish Diseases; Disease Resistance; Vibrio Infections; Flatfishes; Microbiota; Vibrio; Fish Proteins; Proteome; Proteomics
PubMed: 38711504
DOI: 10.3389/fimmu.2024.1352469 -
BMJ Open May 2024The aim of this study is a descriptive presentation of cases of acute watery diarrhoea (AWD) that were presented to Aleppo University Hospital (AUH) during the recent... (Observational Study)
Observational Study
OBJECTIVES
The aim of this study is a descriptive presentation of cases of acute watery diarrhoea (AWD) that were presented to Aleppo University Hospital (AUH) during the recent cholera outbreak in Syria.
DESIGN
Prospective, observational, cohort study.
SETTING AND PARTICIPANTS
A total of 1061 patients with AWD were admitted to AUH during the timeframe of 20 September 2022 to 20 October 2022. The data collection was done through a structured questionnaire. This includes comprehensive clinical observation, laboratory analyses, therapeutic interventions and holistic case evaluations.
RESULTS
The analysis has revealed notable insights: a predominant proportion of patients (58.6%) were residents from urban areas and 40.3% were residents from rural areas. Intriguingly, a diverse range of potential infection sources emerged from patient data within our hospital, including uncontrolled well water, vegetables and faecal-oral transmission through contaminated street/fast food. At discharge, most patients were in good health (79.7%), followed by moderate health (17.6%) and poor health (2.3%), with a minimal percentage dying before discharge (0.4%). The most common complications reported at admission and during hospitalisation included electrolyte imbalance (28.2%), followed by severe dehydration (16.3%). In the follow-up period, the majority of patients exhibited good health (81.0%). Older patients (>60 years) had poorer outcomes, with 8.4% having poor health and 4.2% death rate.
CONCLUSIONS
The study found results consistent with previous AWD outbreaks in developing countries like Yemen, Nigeria and Lebanon. Preventative measures like improving water sanitation and hygiene practices are essential to prevent future outbreaks and ease the strain on healthcare systems. Therefore, future studies must investigate the risk factors that increase the spread and the severity of the disease and investigate the best management method.
Topics: Humans; Cholera; Male; Female; Adult; Disease Outbreaks; Prospective Studies; Syria; Adolescent; Diarrhea; Young Adult; Middle Aged; Child; Child, Preschool; Infant; Acute Disease; Aged
PubMed: 38702080
DOI: 10.1136/bmjopen-2023-082385