Microbiology and pathogenesis of Vibrio cholerae infection
- Regina LaRocque, MD, MPH
Regina LaRocque, MD, MPH
- Assistant Professor of Medicine
- Harvard Medical School
- Jason B Harris, MD, MPH
Jason B Harris, MD, MPH
- Assistant Professor of Pediatrics
- Harvard Medical School
Cholera is a rapidly dehydrating diarrheal disease caused by a toxin-producing bacteria, Vibrio cholerae.
The etiologic agent and pathogenesis of infection with toxigenic V. cholerae is reviewed here. The clinical approach to patients with cholera is discussed separately. (See "Overview of cholera".)
Infections due to other strains of V. cholerae that do not cause epidemic cholera, are also discussed elsewhere. (See "Infections due to non-O1/O139 Vibrio cholerae".)
Etiologic agent — V. cholerae is a distinctive, comma-shaped gram-negative rod. Organisms are highly motile and possess a single polar flagellum. V. cholerae is salt-tolerant, requiring NaCl for growth (halophilic) and exists naturally in aquatic environments. While in aquatic environments, V. cholerae may enter a viable but non-culturable form . However, V. cholerae is readily grown from clinical specimens, including stool and rectal swabs, and can be identified in microbiology laboratories using selective media and biochemical tests. (See "Overview of cholera", section on 'Diagnosis'.)
Only cholera toxin-producing (toxigenic) strains of V. cholerae are associated with cholera. While some environmental V. cholerae are toxigenic and capable of causing cholera, most environmental V. cholerae isolates are not toxigenic. Toxigenic strains harbor a filamentous bacteriophage (CTXΦ) which encodes cholera toxin . (See 'Genomic features' below.)To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
Subscribers log in hereLiterature review current through: Sep 2017. | This topic last updated: Oct 06, 2016.References
- Alam M, Sultana M, Nair GB, et al. Viable but nonculturable Vibrio cholerae O1 in biofilms in the aquatic environment and their role in cholera transmission. Proc Natl Acad Sci U S A 2007; 104:17801.
- Waldor MK, Mekalanos JJ. Lysogenic conversion by a filamentous phage encoding cholera toxin. Science 1996; 272:1910.
- Harris JB, LaRocque RC, Qadri F, et al. Cholera. Lancet 2012; 379:2466.
- Lebens M, Karlsson SL, Källgård S, et al. Construction of novel vaccine strains of Vibrio cholerae co-expressing the Inaba and Ogawa serotype antigens. Vaccine 2011; 29:7505.
- Mutreja A, Kim DW, Thomson NR, et al. Evidence for several waves of global transmission in the seventh cholera pandemic. Nature 2011; 477:462.
- Waldor MK, Mekalanos JJ. Emergence of a new cholera pandemic: molecular analysis of virulence determinants in Vibrio cholerae O139 and development of a live vaccine prototype. J Infect Dis 1994; 170:278.
- Heidelberg JF, Eisen JA, Nelson WC, et al. DNA sequence of both chromosomes of the cholera pathogen Vibrio cholerae. Nature 2000; 406:477.
- Karaolis DK, Johnson JA, Bailey CC, et al. A Vibrio cholerae pathogenicity island associated with epidemic and pandemic strains. Proc Natl Acad Sci U S A 1998; 95:3134.
- Herrington DA, Hall RH, Losonsky G, et al. Toxin, toxin-coregulated pili, and the toxR regulon are essential for Vibrio cholerae pathogenesis in humans. J Exp Med 1988; 168:1487.
- Taylor RK, Miller VL, Furlong DB, Mekalanos JJ. Use of phoA gene fusions to identify a pilus colonization factor coordinately regulated with cholera toxin. Proc Natl Acad Sci U S A 1987; 84:2833.
- Waldor MK, Tschäpe H, Mekalanos JJ. A new type of conjugative transposon encodes resistance to sulfamethoxazole, trimethoprim, and streptomycin in Vibrio cholerae O139. J Bacteriol 1996; 178:4157.
- Chin CS, Sorenson J, Harris JB, et al. The origin of the Haitian cholera outbreak strain. N Engl J Med 2011; 364:33.
- Eppinger M, Pearson T, Koenig SS, et al. Genomic epidemiology of the Haitian cholera outbreak: a single introduction followed by rapid, extensive, and continued spread characterized the onset of the epidemic. MBio 2014; 5:e01721.
- Centers for Disease Control and Prevention (CDC). Update: outbreak of cholera ---Haiti, 2010. MMWR Morb Mortal Wkly Rep 2010; 59:1586.
- Levine MM, Kaper JB, Herrington D, et al. Safety, immunogenicity, and efficacy of recombinant live oral cholera vaccines, CVD 103 and CVD 103-HgR. Lancet 1988; 2:467.
- Nelson EJ, Harris JB, Morris JG Jr, et al. Cholera transmission: the host, pathogen and bacteriophage dynamic. Nat Rev Microbiol 2009; 7:693.
- Levine MM, Kaper JB, Black RE, Clements ML. New knowledge on pathogenesis of bacterial enteric infections as applied to vaccine development. Microbiol Rev 1983; 47:510.
- Krebs SJ, Taylor RK. Protection and attachment of Vibrio cholerae mediated by the toxin-coregulated pilus in the infant mouse model. J Bacteriol 2011; 193:5260.
- Bishop AL, Schild S, Patimalla B, et al. Mucosal immunization with Vibrio cholerae outer membrane vesicles provides maternal protection mediated by antilipopolysaccharide antibodies that inhibit bacterial motility. Infect Immun 2010; 78:4402.
- Gill DM. The arrangement of subunits in cholera toxin. Biochemistry 1976; 15:1242.
- Holmgren J, Lönnroth I, Månsson J, Svennerholm L. Interaction of cholera toxin and membrane GM1 ganglioside of small intestine. Proc Natl Acad Sci U S A 1975; 72:2520.
- Feng Y, Jadhav AP, Rodighiero C, et al. Retrograde transport of cholera toxin from the plasma membrane to the endoplasmic reticulum requires the trans-Golgi network but not the Golgi apparatus in Exo2-treated cells. EMBO Rep 2004; 5:596.
- Gill DM, Meren R. ADP-ribosylation of membrane proteins catalyzed by cholera toxin: basis of the activation of adenylate cyclase. Proc Natl Acad Sci U S A 1978; 75:3050.
- Ma T, Thiagarajah JR, Yang H, et al. Thiazolidinone CFTR inhibitor identified by high-throughput screening blocks cholera toxin-induced intestinal fluid secretion. J Clin Invest 2002; 110:1651.
- Molla AM, Rahman M, Sarker SA, et al. Stool electrolyte content and purging rates in diarrhea caused by rotavirus, enterotoxigenic E. coli, and V. cholerae in children. J Pediatr 1981; 98:835.
- DiRita VJ, Parsot C, Jander G, Mekalanos JJ. Regulatory cascade controls virulence in Vibrio cholerae. Proc Natl Acad Sci U S A 1991; 88:5403.
- Merrell DS, Butler SM, Qadri F, et al. Host-induced epidemic spread of the cholera bacterium. Nature 2002; 417:642.
- Merrell DS, Camilli A. The cadA gene of Vibrio cholerae is induced during infection and plays a role in acid tolerance. Mol Microbiol 1999; 34:836.
- Nelson EJ, Chowdhury A, Flynn J, et al. Transmission of Vibrio cholerae is antagonized by lytic phage and entry into the aquatic environment. PLoS Pathog 2008; 4:e1000187.
- Hartley DM, Morris JG Jr, Smith DL. Hyperinfectivity: a critical element in the ability of V. cholerae to cause epidemics? PLoS Med 2006; 3:e7.
- Butler SM, Nelson EJ, Chowdhury N, et al. Cholera stool bacteria repress chemotaxis to increase infectivity. Mol Microbiol 2006; 60:417.
- Levine MM, Black RE, Clements ML, et al. Duration of infection-derived immunity to cholera. J Infect Dis 1981; 143:818.
- Glass RI, Becker S, Huq MI, et al. Endemic cholera in rural Bangladesh, 1966-1980. Am J Epidemiol 1982; 116:959.
- Ali M, Emch M, Park JK, et al. Natural cholera infection-derived immunity in an endemic setting. J Infect Dis 2011; 204:912.
- Glass RI, Holmgren J, Haley CE, et al. Predisposition for cholera of individuals with O blood group. Possible evolutionary significance. Am J Epidemiol 1985; 121:791.
- Harris JB, Khan AI, LaRocque RC, et al. Blood group, immunity, and risk of infection with Vibrio cholerae in an area of endemicity. Infect Immun 2005; 73:7422.
- Kuhlmann FM, Santhanam S, Kumar P, et al. Blood Group O-Dependent Cellular Responses to Cholera Toxin: Parallel Clinical and Epidemiological Links to Severe Cholera. Am J Trop Med Hyg 2016; 95:440.
- Larocque RC, Sabeti P, Duggal P, et al. A variant in long palate, lung and nasal epithelium clone 1 is associated with cholera in a Bangladeshi population. Genes Immun 2009; 10:267.
- Karlsson EK, Harris JB, Tabrizi S, et al. Natural selection in a bangladeshi population from the cholera-endemic ganges river delta. Sci Transl Med 2013; 5:192ra86.
- Bavishi C, Dupont HL. Systematic review: the use of proton pump inhibitors and increased susceptibility to enteric infection. Aliment Pharmacol Ther 2011; 34:1269.
- Glass RI, Svennerholm AM, Stoll BJ, et al. Protection against cholera in breast-fed children by antibodies in breast milk. N Engl J Med 1983; 308:1389.
- Harris JB, LaRocque RC, Chowdhury F, et al. Susceptibility to Vibrio cholerae infection in a cohort of household contacts of patients with cholera in Bangladesh. PLoS Negl Trop Dis 2008; 2:e221.
- David LA, Weil A, Ryan ET, et al. Gut microbial succession follows acute secretory diarrhea in humans. MBio 2015; 6:e00381.
- Hsiao A, Ahmed AM, Subramanian S, et al. Members of the human gut microbiota involved in recovery from Vibrio cholerae infection. Nature 2014; 515:423.
- Seed KD, Bodi KL, Kropinski AM, et al. Evidence of a dominant lineage of Vibrio cholerae-specific lytic bacteriophages shed by cholera patients over a 10-year period in Dhaka, Bangladesh. MBio 2011; 2:e00334.
- Faruque SM, Islam MJ, Ahmad QS, et al. Self-limiting nature of seasonal cholera epidemics: Role of host-mediated amplification of phage. Proc Natl Acad Sci U S A 2005; 102:6119.
- Faruque SM, Naser IB, Islam MJ, et al. Seasonal epidemics of cholera inversely correlate with the prevalence of environmental cholera phages. Proc Natl Acad Sci U S A 2005; 102:1702.
- Seed KD, Yen M, Shapiro BJ, et al. Evolutionary consequences of intra-patient phage predation on microbial populations. Elife 2014; 3:e03497.
- Etiologic agent
- - Serogroup O1
- - Serogroup O139
- Genomic features
- Molecular epidemiology
- Cholera toxin
- Regulation of virulence
- Host susceptibility
- Interactions with other microbes
- - Gut microbiota
- - Lytic bacteriophages