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1.
Microbiology (Reading) ; 168(2)2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-35113781

RESUMEN

Vibrio cholerae O1 and O139 isolates deploy cholera toxin (CT) and toxin-coregulated pilus (TCP) to cause the diarrhoeal disease cholera. The ctxAB and tcpA genes encoding CT and TCP are part of two acquired genetic elements, the CTX phage and Vibrio pathogenicity island-1 (VPI-1), respectively. ToxR and ToxT proteins are the key regulators of virulence genes of V. cholerae O1 and O139. V. cholerae isolates belonging to serogroups other than O1/O139, called non-O1/non-O139, are usually devoid of virulence-related elements and are non-pathogenic. Here, we have analysed the available whole genome sequence of an environmental toxigenic V. cholerae non-O1/non-O139 strain, VCE232, carrying the CTX phage and VPI-1. Extensive bioinformatics and phylogenetic analyses indicated high similarity of the VCE232 genome sequence with the genome of V. cholerae O1 strains, including organization of the VPI-1 locus, ctxAB, tcpA and toxT genes, and promoters. We established that the VCE232 strain produces an optimal amount of CT at 30 °C under AKI conditions. To investigate the role of ToxT and ToxR in the regulation of virulence factors, we constructed ΔtoxT, ΔtoxR and ΔtoxTΔtoxR deletion mutants of VCE232. Extensive genetic analyses of these mutants indicated that the toxT and toxR genes of VCE232 are crucial for CT and TCP production. However, unlike O1 isolates, the presence of either toxT or toxR gene is sufficient for optimal CT production in VCE232. In addition, the VCE232 ΔtoxR mutant showed differential regulation of the major outer membrane proteins, OmpT and OmpU. This is the first attempt to explore the regulation of expression of major virulence genes and regulators in an environmental toxigenic V. cholerae non-O1/non-O139 strain.


Asunto(s)
Cólera , Vibrio cholerae no O1 , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Humanos , Filogenia , Vibrio cholerae no O1/metabolismo , Virulencia/genética
3.
Front Public Health ; 10: 845057, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35602140

RESUMEN

Introduction: Cholera remains a serious public health problem characterized by a large disease burden, frequent outbreaks, persistent endemicity, and high mortality, particularly in tropical and subtropical low-income countries including Ethiopia. The recent cholera outbreak in the Somali region began on 4 September to 1 November 2019. Cholera may spread rapidly through a population so that an early detection and reporting of the cases is mandatory. This study aimed to identify determinants of cholera infection among >5 years of age population in Somali region, Ethiopia. Methods: A community-based unmatched case-control study was conducted among 228 (76 cases and 152 controls, 1:2 ratio) systematically selected population. Data were collected using a structured questionnaire administered by an interviewer and a record review. Descriptive statistics and multivariable logistic regression analysis was used to identify the determinants of the risk factors of cholera infection with a 95% confidence interval and statistical significance was declared a tap-value < 0.05. Results: A total of 228 participants (33.3% cases and 66.7% controls) were enrolled in this study. The majority of the cases were in the range of 20-49 years of age (69.7%). The odds of acquiring cholera infection increased significantly by drinking unsafe pipe water (AOR 4.3, 95% CI 1.65-11.2), not having a household level toilet/latrine (AOR 3.25, 95% CI 1.57-6.76), hand washing only sometimes after the toilet (AOR 3.04, 95% CI 1.58-5.86) and not using water purification methods (AOR 2.3, 95% CI 1.13-4.54). Conclusion: Major risk factors for cholera infection were related to drinking water and latrine hygiene. Improvement in awareness creation about cholera prevention and control methods, including water treatment, hygiene and sanitation were crucial in combating this cholera outbreak. Primary public health actions are ensuring clean drinking water, delivery of water purification tablets, soap and hand sanitizers and provision of health care and outbreak response. Long term goals in cholera affected areas include comprehensive water and sanitation strategies. Overall, the strategic role of a multi-sectoral approach in the design and implementation of public health interventions aimed at preventing and controlling cholera are essential to avert cholera outbreaks. Preparedness should be highlighted in cholera prone areas like Somali region especially after drought periods.


Asunto(s)
Cólera , Agua Potable , Estudios de Casos y Controles , Cólera/epidemiología , Cólera/etiología , Cólera/prevención & control , Diarrea/prevención & control , Brotes de Enfermedades , Etiopía/epidemiología , Desinfección de las Manos , Humanos , Somalia , Cuartos de Baño
5.
Antimicrob Resist Infect Control ; 11(1): 62, 2022 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-35468830

RESUMEN

BACKGROUND: Vibrio cholerae O1/O139 were the predominant circulating serogroups exhibiting multi-drug resistance (MDR) during the cholera outbreak which led to cholera treatment failures. OBJECTIVE: This meta-analysis aimed to evaluate the weighted pooled resistance (WPR) rates in V. cholerae O1/O139 isolates obtained from environmental samples. METHODS: We systematically searched the articles in PubMed, Scopus, and Embase (until January 2020). Subgroup analyses were then employed by publication year, geographic areas, and the quality of studies. Statistical analyses were conducted using STATA software (ver. 14.0). RESULTS: A total of 20 studies investigating 648 environmental V. cholerae O1/O139 isolates were analysed. The majority of the studies were originated from Asia (n = 9). In addition, a large number of studies (n = 15 i.e. 71.4%) included in the meta-analysis revealed the resistance to cotrimoxazole and ciprofloxacin. The WPR rates were as follows: cotrimoxazole 59%, erythromycin 28%, tetracycline 14%, doxycycline 5%, and ciprofloxacin 0%. There was increased resistance to nalidixic acid, cotrimoxazole, furazolidone, and tetracycline while a decreased resistance to amoxicillin, ciprofloxacin, erythromycin, chloramphenicol, ampicillin, streptomycin, and ceftriaxone was observed during the years 2000-2020. A significant decrease in the doxycycline and ciprofloxacin-resistance rates in V. cholerae O1/O139 isolates was reported over the years 2011-2020 which represents a decrease in 2001-2010 (p < 0.05). CONCLUSIONS: Fluoroquinolones, gentamicin, ceftriaxone, doxycycline, kanamycin, and cefotaxime showed the highest effectiveness and the lowest resistance rate. However, the main interest is the rise of antimicrobial resistance in V. cholerae strains especially in low-income countries or endemic areas, and therefore, continuous surveillance, careful appropriate AST, and limitation on improper antibiotic usage are crucial.


Asunto(s)
Cólera , Vibrio cholerae O139 , Vibrio cholerae O1 , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Ceftriaxona/uso terapéutico , Cólera/tratamiento farmacológico , Cólera/epidemiología , Ciprofloxacina , Doxiciclina , Farmacorresistencia Bacteriana , Eritromicina , Humanos , Pruebas de Sensibilidad Microbiana , Combinación Trimetoprim y Sulfametoxazol/uso terapéutico , Vibrio cholerae O1/genética
6.
Nature ; 604(7905): 250-252, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35388150
7.
Front Cell Infect Microbiol ; 12: 863435, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35433512

RESUMEN

There is a growing demand for rapid, sensitive, field-deployable nucleic acid tests for cholera, which usually occurs in rural areas. In this study, we developed a Cas12a-assisted rapid isothermal detection (CARID) system for the detection of toxigenic V. cholerae serogroups O1 and O139 by combining recombinase-aided amplification and CRISPR-Cas (clustered regularly interspaced short palindromic repeats and CRISPR-associated proteins). The results can be determined by fluorescence signal and visualized by lateral flow dipstick. We identified 154 V. cholerae strains and 129 strains of other intestinal diarrheagenic bacteria with a 100% coincidence rate. The limit of detection of CARID was 20 copies/reaction of V. cholerae genomic DNA, which is comparable to that of polymerase chain reaction (PCR) and qPCR. Multiple-CARID was also established for efficiency and economic considerations with an acceptable decrease in sensitivity. Simulated sample tests showed that CARID is suitable for complex samples. In conclusion, CARID is a rapid, sensitive, economically efficient, and portable method for the detection of V. cholerae, which makes it suitable for field responses to cholera.


Asunto(s)
Cólera , Vibrio cholerae O1 , Cólera/diagnóstico , Cólera/microbiología , Toxina del Cólera , Humanos , Serogrupo , Serotipificación , Vibrio cholerae O1/genética
8.
mBio ; 13(2): e0053922, 2022 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-35389261

RESUMEN

Human challenge studies are instrumental for testing cholera vaccines, but these studies use outdated strains and require inpatient facilities. Here, we created next-generation isogenic Ogawa and Inaba O1 V. cholerae challenge strains (ZChol strains) derived from a contemporary Zambian clinical isolate representative of current dominant pandemic V. cholerae. Since the primary mechanism of immune protection against cholera is thought to be antibody responses that limit V. cholerae colonization and not the diarrheagenic actions of cholera toxin, these strains were rendered nontoxigenic. In infant mice, the ZChol strains did not cause diarrhea and proved to accurately gauge reduction in intestinal colonization mediated by effective vaccination. ZChol strains were also valuable as targets for measuring vibriocidal antibody responses. Using barcoded ZChol strains, we discovered that vaccination and passive immunity in the infant mouse model tightens the infection bottleneck without restricting pathogen expansion during intestinal infection. Collectively, our findings suggest that ZChol strains have the potential to enhance the safety, relevance, and scope of future cholera vaccine challenge studies and be valuable reagents for studies of immunity to cholera. IMPORTANCE Human challenge studies are a valuable method for testing the efficacy of cholera vaccines. However, challenge studies cannot be performed in countries of cholera endemicity due to safety concerns; also, contemporary pandemic Vibrio cholerae strains are not used in current challenge studies. To facilitate cholera research, we derived nontoxigenic challenge strains of both V. cholerae serotypes from a 2016 clinical isolate from Zambia and demonstrated how they can be used to gauge cholera immunity accurately and safely. These strains were also genetically barcoded, adding the potential for analyses of V. cholerae population dynamics to challenge studies. Preclinical analyses presented here suggest that these strains have the potential to enhance the safety, relevance, and scope of future cholera vaccine challenge studies and be valuable reagents for studies of immunity to cholera.


Asunto(s)
Vacunas contra el Cólera , Cólera , Vibrio cholerae , Animales , Cólera/epidemiología , Toxina del Cólera , Humanos , Ratones , Vibrio cholerae/genética
9.
Int J Infect Dis ; 120: 83-87, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35429638

RESUMEN

OBJECTIVES: The non-O1/non-O139 Vibrio cholerae caused outbreaks or sporadic cases of gastroenteritis that was rarely seen in good sanitary condition. It was described a case of systemic multiple organ lesions that worsened because of non-O1/non-O139 V. cholerae, suggesting that serogroups have a potential virulence in enhancing pathogenicity with patients with underlying diseases compared with a healthy population. DESIGN OR METHODS: Samples are identified by strain culture, polymerase chain reaction (PCR) virulence identification, and whole genome sequencing. RESULTS: A middle-aged man was diagnosed with cytotoxin-producing and nontoxin V. cholerae non-O1/non-O139 serogroups. Although lacking the CT toxin encoded by ctxAB gene, the pathogenesis of cholera relies on the synergistic action of many other genes, especially virulence genes. CONCLUSIONS: This case suggested that the laborers engaging in agricultural production are at potential risk of V. cholerae infection by exposure of open wounds to contaminated water . However, epidemiological investigation should focus on the objective cause of the change of working environment. Furthermore, common diseases can possibly enhance the virulence of non-O1/non-O139 serogroups by attacking the tight junction of small intestinal epithelial cells, further triggering bacteremia, a process that may lead to death within 48-72 hours, which requires great attention.


Asunto(s)
Cólera , Vibrio cholerae no O1 , Cólera/epidemiología , Toxina del Cólera/genética , Endotoxinas , Agricultores , Humanos , Masculino , Persona de Mediana Edad , Vibrio cholerae no O1/genética
10.
Syst Rev ; 11(1): 73, 2022 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-35436979

RESUMEN

BACKGROUND: Waterborne diarrhea diseases are among the leading causes of morbidity and mortality globally. These diseases can be mitigated by implementing various interventions. We reviewed the literature to identify available interventions to mitigate the risk of waterborne diarrheal diseases. METHODS: We conducted a systematic database review of CINAHL (Cumulative Index to Nursing and Allied Health Literature), PubMed, Web of Science Core Collection, Cochrane library, Scopus, African Index Medicus (AIM), and LILACS (Latin American and Caribbean Health Sciences Literature). Our search was limited to articles published between 2009 and 2020. We conducted the review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement checklist. The identified studies were qualitatively synthesized. RESULTS: Our initial search returned 28 773 articles of which 56 studies met the inclusion criteria. The included studies reported interventions, including vaccines for rotavirus disease (monovalent, pentavalent, and Lanzhou lamb vaccine); enhanced water filtration for preventing cryptosporidiosis, Vi polysaccharide for typhoid; cholera 2-dose vaccines, water supply, water treatment and safe storage, household disinfection, and hygiene promotion for controlling cholera outbreaks. CONCLUSION: We retrieved few studies on interventions against waterborne diarrheal diseases in low-income countries. Interventions must be specific to each type of waterborne diarrheal disease to be effective. Stakeholders must ensure collaboration in providing and implementing multiple interventions for the best outcomes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020190411 .


Asunto(s)
Cólera , Vacunas , Animales , Región del Caribe , Cólera/prevención & control , Diarrea/prevención & control , Brotes de Enfermedades , Humanos , Ovinos
11.
Nature ; 604(7905): 323-329, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35388218

RESUMEN

Horizontal gene transfer can trigger rapid shifts in bacterial evolution. Driven by a variety of mobile genetic elements-in particular bacteriophages and plasmids-the ability to share genes within and across species underpins the exceptional adaptability of bacteria. Nevertheless, invasive mobile genetic elements can also present grave risks to the host; bacteria have therefore evolved a vast array of defences against these elements1. Here we identify two plasmid defence systems conserved in the Vibrio cholerae El Tor strains responsible for the ongoing seventh cholera pandemic2-4. These systems, termed DdmABC and DdmDE, are encoded on two major pathogenicity islands that are a hallmark of current pandemic strains. We show that the modules cooperate to rapidly eliminate small multicopy plasmids by degradation. Moreover, the DdmABC system is widespread and can defend against bacteriophage infection by triggering cell suicide (abortive infection, or Abi). Notably, we go on to show that, through an Abi-like mechanism, DdmABC increases the burden of large low-copy-number conjugative plasmids, including a broad-host IncC multidrug resistance plasmid, which creates a fitness disadvantage that counterselects against plasmid-carrying cells. Our results answer the long-standing question of why plasmids, although abundant in environmental strains, are rare in pandemic strains; have implications for understanding the dissemination of antibiotic resistance plasmids; and provide insights into how the interplay between two defence systems has shaped the evolution of the most successful lineage of pandemic V. cholerae.


Asunto(s)
Cólera , Vibrio cholerae , Cólera/epidemiología , Cólera/microbiología , Islas Genómicas/genética , Humanos , Pandemias , Plásmidos/genética , Vibrio cholerae/genética
12.
Lancet ; 399(10333): 1429-1440, 2022 04 09.
Artículo en Inglés | MEDLINE | ID: mdl-35397865

RESUMEN

Cholera was first described in the areas around the Bay of Bengal and spread globally, resulting in seven pandemics during the past two centuries. It is caused by toxigenic Vibrio cholerae O1 or O139 bacteria. Cholera is characterised by mild to potentially fatal acute watery diarrhoeal disease. Prompt rehydration therapy is the cornerstone of management. We present an overview of cholera and its pathogenesis, natural history, bacteriology, and epidemiology, while highlighting advances over the past 10 years in molecular epidemiology, immunology, and vaccine development and deployment. Since 2014, the Global Task Force on Cholera Control, a WHO coordinated network of partners, has been working with several countries to develop national cholera control strategies. The global roadmap for cholera control focuses on stopping transmission in cholera hotspots through vaccination and improved water, sanitation, and hygiene, with the aim to reduce cholera deaths by 90% and eliminate local transmission in at least 20 countries by 2030.


Asunto(s)
Cólera , Vibrio cholerae , Cólera/epidemiología , Cólera/prevención & control , Diarrea/epidemiología , Humanos , Epidemiología Molecular , Saneamiento
13.
J Math Biol ; 84(5): 34, 2022 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-35381862

RESUMEN

Cholera is a water- and food-borne infectious disease caused by V. cholerae. To investigate multiple effects of human behavior change, seasonality and spatial heterogeneity on cholera spread, we propose a reaction-advection-diffusion model that incorporates human hosts and aquatic reservoir of V. cholerae. We derive the basic reproduction number [Formula: see text] for this system and then establish a threshold type result on its global dynamics in terms of [Formula: see text]. Further, we show that the bacterial loss at the downstream end of the river due to water flux can reduce the disease risk, and describe the asymptotic behavior of [Formula: see text] for small and large diffusion in a special case (where the diffusion rates of infected human and the pathogen are constant). We also study the transmission dynamics at the early stage of cholera outbreak numerically, and find that human behavior change may lower the infection level and delay the disease peak. Moreover, the relative rate of bacterial loss, together with convection rate, plays an important role in identifying the severely infected areas. Meanwhile spatial heterogeneity may dilute or amplify cholera infection, which in turn would increase the complexity of disease spread.


Asunto(s)
Cólera , Epidemias , Vibrio cholerae , Número Básico de Reproducción , Cólera/epidemiología , Humanos , Modelos Biológicos
14.
PLoS One ; 17(4): e0266849, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35413080

RESUMEN

BACKGROUND: Handwashing with soap has the potential to curb cholera transmission. This research explores how populations experienced and responded to the 2017 cholera outbreak in the Democratic Republic of the Congo and how this affected their handwashing behaviour. METHODS: Cholera cases were identified through local cholera treatment centre records. Comparison individuals were recruited from the same neighbourhoods by identifying households with no recent confirmed or suspected cholera cases. Multiple qualitative methods were employed to understand hand hygiene practices and their determinants, including unstructured observations, interviews and focus group discussions. The data collection tools and analysis were informed by the Behaviour Centred Design Framework. Comparisons were made between the experiences and practices of people from case households and participants from comparison households. RESULTS: Cholera was well understood by the population and viewed as a persistent and common health challenge. Handwashing with soap was generally observed to be rare during the outbreak despite self-reported increases in behaviour. Across case and comparison groups, individuals were unable to prioritise handwashing due to competing food-scarcity and livelihood challenges and there was little in the physical or social environments to cue handwashing or make it a convenient, rewarding or desirable to practice. The ability of people from case households to practice handwashing was further constrained by their exposure to cholera which in addition to illness, caused profound non-health impacts to household income, productivity, social status, and their sense of control. CONCLUSIONS: Even though cholera outbreaks can cause disruptions to many determinants of behaviour, these shifts do not automatically facilitate an increase in preventative behaviours like handwashing with soap. Hygiene programmes targeting outbreaks within complex crises could be strengthened by acknowledging the emic experiences of the disease and adopting sustainable solutions which build upon local disease coping mechanisms.


Asunto(s)
Cólera , Cólera/epidemiología , Cólera/prevención & control , República Democrática del Congo/epidemiología , Brotes de Enfermedades/prevención & control , Desinfección de las Manos/métodos , Humanos , Jabones
15.
PLoS Negl Trop Dis ; 16(4): e0010358, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35442958

RESUMEN

BACKGROUND: A global stockpile of oral cholera vaccine (OCV) was established in 2013 for use in outbreak response and are licensed as two-dose regimens. Vaccine availability, however, remains limited. Previous studies have found that a single dose of OCV may provide substantial protection against cholera. METHODS: Using a mathematical model with two age groups paired with optimization algorithms, we determine the optimal vaccination strategy with one and two doses of vaccine to minimize cumulative overall infections, symptomatic infections, and deaths. We explore counterfactual vaccination scenarios in three distinct settings: Maela, the largest refugee camp in Thailand, with high in- and out-migration; N'Djamena, Chad, a densely populated region; and Haiti, where departments are connected by rivers and roads. RESULTS: Over the short term under limited vaccine supply, the optimal strategies for all objectives prioritize one dose to the older age group (over five years old), irrespective of setting and level of vaccination coverage. As more vaccine becomes available, it is optimal to administer a second dose for long-term protection. With enough vaccine to cover the whole population with one dose, the optimal strategies can avert up to 30% to 90% of deaths and 36% to 92% of symptomatic infections across the three settings over one year. The one-dose optimal strategies can avert 1.2 to 1.8 times as many cases and deaths compared to the standard two-dose strategy. CONCLUSIONS: In an outbreak setting, speedy vaccination campaigns with a single dose of OCV is likely to avert more cases and deaths than a two-dose pro-rata campaign under a limited vaccine supply.


Asunto(s)
Vacunas contra el Cólera , Cólera , Administración Oral , Anciano , Preescolar , Cólera/epidemiología , Cólera/prevención & control , Brotes de Enfermedades/prevención & control , Humanos , Programas de Inmunización
16.
Toxins (Basel) ; 14(3)2022 03 18.
Artículo en Inglés | MEDLINE | ID: mdl-35324722

RESUMEN

Vibrio cholerae uses cholera toxin (CT) to cause cholera, a severe diarrheal disease in humans that can lead to death within hours of the onset of symptoms. The catalytic activity of CT in target epithelial cells increases cellular levels of 3',5'-cyclic AMP (cAMP), leading to the activation of the cystic fibrosis transmembrane conductance regulator (CFTR), an apical ion channel that transports chloride out of epithelial cells, resulting in an electrolyte imbalance in the intestinal lumen and massive water loss. Here we report that when administered perorally, benzopyrimido-pyrrolo-oxazinedione, (R)-BPO-27), a potent small molecule inhibitor of CFTR, blocked disease symptoms in a mouse model for acute diarrhea caused by toxigenic V. cholerae. We show that both (R)-BPO-27 and its racemic mixture, (R/S)-BPO-27, are able to protect mice from CT-dependent diarrheal disease and death. Furthermore, we show that, consistent with the ability of the compound to block the secretory diarrhea induced by CT, BPO-27 has a measurable effect on suppressing the gut replication and survival of V. cholerae, including a 2010 isolate from Haiti that is representative of the most predominant 'variant strains' that are causing epidemic and pandemic cholera worldwide. Our results suggest that BPO-27 should advance to human Phase I studies that could further address its safety and efficacy as therapeutic or preventative drug intervention for diarrheal syndromes, including cholera, that are mediated by CFTR channel activation.


Asunto(s)
Cólera , Vibrio cholerae , Animales , Cólera/tratamiento farmacológico , Toxina del Cólera/uso terapéutico , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/uso terapéutico , Diarrea/tratamiento farmacológico , Ratones , Morbilidad , Vibrio cholerae/metabolismo
17.
Microbiol Spectr ; 10(2): e0039122, 2022 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-35315699

RESUMEN

Comparative genomic analysis of Vibrio cholerae El Tor associated with endemic cholera in Asia revealed two distinct lineages, one dominant in Bangladesh and the other in India. An in-depth whole-genome study of V. cholerae El Tor strains isolated during endemic cholera in Bangladesh (1991 to 2017) included reference genome sequence data obtained online. Core genome phylogeny established using single nucleotide polymorphisms (SNPs) showed V. cholerae El Tor strains comprised two lineages, BD-1 and BD-2, which, according to Bayesian phylodynamic analysis, originated from paraphyletic group BD-0 around 1981. BD-1 and BD-2 lineages overlapped temporally but were negatively associated as causative agents of cholera during 2004 to 2017. Genome-wide association study (GWAS) revealed 140 SNPs and 31 indels, resulting in gene alleles unique to BD-1 and BD-2. Regression analysis of root to tip distance and year of isolation indicated early BD-0 strains at the base, whereas BD-1 and BD-2 subsequently emerged and progressed by accumulating SNPs. Pangenome analysis provided evidence of gene acquisition by both BD-1 and BD-2, of which six crucial proteins of known function were predominant in BD-2. BD-1 and BD-2 diverged and have distinctively different genomic traits, namely, heterogeneity in VSP-2, VPI-1, mobile elements, toxin encoding elements, and total gene abundance. In addition, the observed phage-inducible chromosomal island-like element (PLE1), and SXT ICE elements (ICETET) in BD-2 presumably provided a fitness advantage for the lineage to outcompete BD-1 as the etiological agent of endemic cholera in Bangladesh, with implications for global cholera epidemiology. IMPORTANCE Cholera is a global disease with specific reference to the Bay of Bengal Ganges Delta where Vibrio cholerae O1 El Tor, the causative agent of the disease showed two circulating lineages, one dominant in Bangladesh and the other in India. Results of an in-depth genomic study of V. cholerae associated with endemic cholera during the past 27 years (1991 to 2017) indicate emergence and succession of the two lineages, BD-1 and BD-2, arising from a common ancestral paraphyletic group, BD-0, comprising the early strains and short-term evolution of the bacterium in Bangladesh. Among the two V. cholerae lineages, BD-2 supersedes BD-1 and is predominant in the most recent endemic cholera in Bangladesh. The BD-2 lineage contained significantly more SNPs and indels, and showed richness in gene abundance, including antimicrobial resistance genes, gene cassettes, and PLE to fight against bacteriophage infection, acquired over time. These findings have important epidemic implications on a global scale.


Asunto(s)
Cólera , Vibrio cholerae O1 , Bangladesh/epidemiología , Teorema de Bayes , Cólera/epidemiología , Cólera/microbiología , Toxina del Cólera/genética , Toxina del Cólera/metabolismo , Estudio de Asociación del Genoma Completo , Genómica/métodos , Humanos , Vibrio cholerae O1/genética
18.
Microb Pathog ; 165: 105485, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35318072

RESUMEN

Cholera is a serious epidemic disease caused by the toxigenic strains of Vibrio cholerae belonged to O1 or O139 serogroups. The emergence of antibacterial resistance in V. cholerae is an increasing concern. Natural product drug invention and Ethnopharmacology may demonstrate a considerable expectation under this circumstance. Traditionally, leaves of Typhonium trilobatum (L.) Schott (locally known as Ghatkanchu or Bengal Arum) are employed for treatment of gastrointestinal disorder in different region of India. The objective of the present study was to evaluate the antibacterial, and antibiofilm activities of methanol extract of T. trilobatum leaves (METTL) against the strains of multi-drug resistant (MDR) Vibrio cholerae (serotypes O1, O139, non-O1, and non-O139) which are responsible for watery diarrhea such as cholera. MIC, MBC and time-kill kinetic studies were used for evaluation of In vitro antibacterial activity of METTL. Microdilution method and Confocal laser scanning microscopy were used to evaluate biofilm-inhibitory activities. The gene expression was analyzed by performing Quantitative real-time PCR (qRT-PCR). METTL showed antibacterial activity with MIC and MBC at 1-32 mg/mL and 8-32 mg/mL, respectively against the clinical strains of Vibrio cholerae belonged to different serogroups. METTL showed significant (P < 0.05) inhibitory activity on the formation of biofilm by V. cholerae SG24, with 81.3, 75.8, and 69.6% of inhibition at MIC, ½ MIC and » MIC, respectively. METTL showed also significant (P < 0.05) inhibitory activity on the formation of extracellular polymeric substances (EPS) formation by V. cholerae SG24, with 89.41, and 99.26% of inhibition of EPS protein and EPS carbohydrate at MIC, respectively. METTL significantly (p < 0.01) inhibited the Cholera toxin (CT) production by the V. cholerae strain SG24 evaluated by the CT - ELISA assay. The cholera toxin production was reduced by 76.26%, 48.76% and 29.93 at MIC (8 mg/mL), ½ MIC (4 mg/mL) and » MIC (2 mg/mL), respectively. METTL was shown to repress ctxAB gene transcription 1.76 fold (p < 0.05) at sub-bactericidal concentration (» MIC). We also found that the expression of cholera toxin activator genes, toxT and tcpP was reduced by 11.56- fold (p < 0.001) and 23.52- fold (p < 0.001), respectively, at sub-bactericidal concentration (» MIC). Transcription of the following genes was repressed: vpsR (1.8-fold; p < 0.05), Bap1 (1.53-fold; p ≤ 0.05), and rmbA (2.89-fold) by METTL at sub-bactericidal concentration. The expression of vpsT was also repressed by 1.5-fold (p < 0.01) at sub-bactericidal concentration. The active Typhonium trilobatum (L.) leaves extract may be suggested as an substitute for the treatment of MDR V. cholerae infection and could be used as prospective source for the development of novel antimicrobial compound/s and biofilm-inhibitory drug/s useful for the treatment of cholera and diarrheal patients. The results obtained here also validate scientifically the traditional uses of Typhonium trilobatum (L.) in India employed for the treatment of gastrointestinal disorder. Further studies should be directed at purifying and characterizing these antibacterial principles against Vibrio cholerae.


Asunto(s)
Cólera , Vibrio cholerae , Antibacterianos/farmacología , Cólera/microbiología , Toxina del Cólera/genética , Humanos , Cinética , Extractos Vegetales/farmacología , Estudios Prospectivos , Vibrio cholerae/metabolismo , Virulencia/genética
19.
Elife ; 112022 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-35343438

RESUMEN

Recent studies indicate that the human intestinal microbiota could impact the outcome of infection by Vibrio cholerae, the etiological agent of the diarrheal disease cholera. A commensal bacterium, Paracoccus aminovorans, was previously identified in high abundance in stool collected from individuals infected with V. cholerae when compared to stool from uninfected persons. However, if and how P. aminovorans interacts with V. cholerae has not been experimentally determined; moreover, whether any association between this bacterium alters the behaviors of V. cholerae to affect the disease outcome is unclear. Here, we show that P. aminovorans and V. cholerae together form dual-species biofilm structure at the air-liquid interface, with previously uncharacterized novel features. Importantly, the presence of P. aminovorans within the murine small intestine enhances V. cholerae colonization in the same niche that is dependent on the Vibrio exopolysaccharide and other major components of mature V. cholerae biofilm. These studies illustrate that multispecies biofilm formation is a plausible mechanism used by a gut microbe to increase the virulence of the pathogen, and this interaction may alter outcomes in enteric infections.


Asunto(s)
Cólera , Microbioma Gastrointestinal , Vibrio cholerae , Animales , Biopelículas , Cólera/microbiología , Humanos , Ratones , Virulencia
20.
PLoS One ; 17(3): e0265868, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35333909

RESUMEN

BACKGROUND: Cholera continues to cause morbidity and mortality in developing countries, including Tanzania. Since August 2015, Tanzania Mainland has experienced cholera outbreaks affecting 26 regions and a 1.6% case fatality rate. The current study determined the virulence factors, genetic relatedness and antimicrobial susceptibility patterns of the Vibrio cholerae isolated from different regions in Tanzania. METHODS: A cross-sectional study that involved the genetic characterization of V. cholerae isolates from eleven regions in Tanzania was carried out. There were 99 V. cholerae isolates collected between January 2016 and December 2017. The study perfomed a Multi-locus Variable-number tandem-repeat analysis for genetic relatedness and Mismatch Amplification Mutation Analysis polymerase chain reaction for analyzing toxin genes. All the isolates were tested for antimicrobial susceptibility using the Kirby Bauer disk diffusion method. Data were generally analyzed using Microsoft excel, where genetic relatedness was analyzed using eBurst software v3. RESULTS: All isolates were V. cholerae O1. Ogawa was the most predominant 97(98%) serotype. Isolates were genetically related with a small genetic diversity and were positive for ctxA, tcpA El Tor virulence genes. All isolates (100%) were sensitive to doxycycline, trimethoprim-sulphamethoxazole, tetracycline, ceftriaxone, and chloramphenicol, while 87.8% were sensitive to ciprofloxacin. A high resistance rate (100%) was detected towards erythromycin, nalidixic acid, amoxicillin, and ampicillin. CONCLUSION: The V.cholerae O1 serotypes Ogawa, El Tor variant predominantly caused cholera outbreaks in Tanzania with strains clonally related regardless of the place and time of the outbreak. Most of the isolates were susceptible to the antibiotic regimen currently used in Tanzania. The high resistance rate detected for the other common antibiotics calls for continuous antimicrobial susceptibility testing during outbreaks.


Asunto(s)
Cólera , Vibrio cholerae O1 , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Cólera/tratamiento farmacológico , Cólera/epidemiología , Toxina del Cólera/genética , Estudios Transversales , Brotes de Enfermedades , Genotipo , Humanos , Pruebas de Sensibilidad Microbiana , Tanzanía/epidemiología , Factores de Virulencia/genética
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