Abstract
Cholera is a bacterial infection that has sickened and killed millions of individuals since ancient times. It is caused by the Gram-negative bacterium Vibrio cholerae and is transmitted by the fecal-oral route, mainly through contaminated drinking water. Colonization of the human small intestine by Vibrio cholerae requires presence of the toxin-coregulated pilus (TCP) and allows for multiplication of the bacterium. As it multiplies, V. cholerae secretes cholera toxin (CT), which targets heterotrimeric G proteins and induces production of cyclic AMP. Buildup of this molecule leads to secretion of chloride ions into the intestinal lumen, which in turn prompts massive fluid loss in the form of secretory diarrhea. In some cases, patients can lose a liter of fluid every hour and quickly become severely dehydrated, often resulting in death. Over the past several decades, cholera fatality rates have dropped significantly due to the introduction of oral rehydration therapy, an inexpensive and effective method of treatment. Two vaccines, Dukoral and Shanchol, are currently recommended by the World Health Organization (WHO) for prevention of cholera. Both are oral heat-killed whole-cell vaccines that provide >50 % protection when administered correctly. However, cholera is still a grave problem in areas where water sanitation is insufficient, such as developing countries and regions where conflict or natural disasters have damaged infrastructure.
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Anderson C (1991) Cholera epidemic traced to risk miscalculation. Nature 354(6351):255. doi:10.1038/354255a0
Ang GY, Yu CY, Balqis K, Elina HT, Azura H, Hani MH, Yean CY (2010) Molecular evidence of cholera outbreak caused by a toxigenic Vibrio cholerae O1 El tor variant strain in Kelantan, Malaysia. J Clin Microbiol 48(11):3963–3969. doi:10.1128/JCM.01086-10
Bishop AL, Camilli A (2011) Vibrio cholerae: lessons for mucosal vaccine design. Expert Rev Vaccines 10(1):79–94. doi:10.1586/erv.10.150
Bourassa L, Camilli A (2009) Glycogen contributes to the environmental persistence and transmission of Vibrio cholerae. Mol Microbiol 72(1):124–138. doi:10.1111/j.1365-2958.2009.06629.x, MMI6629 [pii]
Bradley ES, Bodi K, Ismail AM, Camilli A (2011) A genome-wide approach to discovery of small RNAs involved in regulation of virulence in Vibrio cholerae. PLoS Pathog 7(7):e1002126. doi:10.1371/journal.ppat.1002126 PPATHOGENS-D-11-00072 [pii]
Butler D (2011) No quick fix for Haiti cholera. Nature 478(7369):295–296. doi:10.1038/478295a
Chin CS, Sorenson J, Harris JB, Robins WP, Charles RC, Jean-Charles RR, Bullard J, Webster DR, Kasarskis A, Peluso P, Paxinos EE, Yamaichi Y, Calderwood SB, Mekalanos JJ, Schadt EE, Waldor MK (2011) The origin of the Haitian cholera outbreak strain. N Engl J Med 364(1):33–42. doi:10.1056/NEJMoa1012928
Clemens JD, Sack DA, Harris JR, Chakraborty J, Khan MR, Stanton BF, Kay BA, Khan MU, Yunus M, Atkinson W et al (1986) Field trial of oral cholera vaccines in Bangladesh. Lancet 2(8499):124–127
da Cunha Ferreira RM, Cash RA (1990) History of the development of oral rehydration therapy. Clin Ther 12(Suppl A):2–11; discussion 11–13
De SN (1959) Enterotoxicity of bacteria-free culture-filtrate of Vibrio cholerae. Nature 183(4674):1533–1534
De Haan L, Hirst TR (2004) Cholera toxin: a paradigm for multi-functional engagement of cellular mechanisms (Review). Mol Membr Biol 21(2):77–92. doi:10.1080/09687680410001663267, 0V4XABL5376HCVH4 [pii]
DiRita VJ, Parsot C, Jander G, Mekalanos JJ (1991) Regulatory cascade controls virulence in Vibrio cholerae. Proc Natl Acad Sci USA 88(12):5403–5407
Duffy J (1971) The history of Asiatic cholera in the United States. Bull N Y Acad Med 47(10):1152–1168
Dziejman M, Balon E, Boyd D, Fraser CM, Heidelberg JF, Mekalanos JJ (2002) Comparative genomic analysis of Vibrio cholerae: genes that correlate with cholera endemic and pandemic disease. Proc Natl Acad Sci USA 99(3):1556–1561. doi:10.1073/pnas.042667999
Faruque SM, Naser IB, Islam MJ, Faruque AS, Ghosh AN, Nair GB, Sack DA, Mekalanos JJ (2005) Seasonal epidemics of cholera inversely correlate with the prevalence of environmental cholera phages. Proc Natl Acad Sci USA 102(5):1702–1707. doi:10.1073/pnas.0408992102
Finkelstein RA, LoSpalluto JJ (1969) Pathogenesis of experimental cholera. Preparation and isolation of choleragen and choleragenoid. J Exp Med 130(1):185–202
Goel AK, Jain M, Kumar P, Sarguna P, Bai M, Ghosh N, Gopalan N (2011) Molecular characterization reveals involvement of altered El Tor biotype Vibrio cholerae O1 strains in cholera outbreak at Hyderabad, India. J Microbiol 49(2):280–284. doi:10.1007/s12275-011-0317-9
Herrington DA, Hall RH, Losonsky G, Mekalanos JJ, Taylor RK, Levine MM (1988) Toxin, toxin-coregulated pili, and the toxR regulon are essential for Vibrio cholerae pathogenesis in humans. J Exp Med 168(4):1487–1492
Higgins DE, Nazareno E, DiRita VJ (1992) The virulence gene activator ToxT from Vibrio cholerae is a member of the AraC family of transcriptional activators. J Bacteriol 174(21):6974–6980
Karaolis DK, Johnson JA, Bailey CC, Boedeker EC, Kaper JB, Reeves PR (1998) A Vibrio cholerae pathogenicity island associated with epidemic and pandemic strains. Proc Natl Acad Sci USA 95(6):3134–3139
Koch R (1884) An address on cholera and its Bacillus. Br Med J 2(1236):453–459
Lacey SW (1995) Cholera: calamitous past, ominous future. Clin Infect Dis 20(5):1409–1419
Legros D, Paquet C, Perea W, Marty I, Mugisha NK, Royer H, Neira M, Ivanoff B (1999) Mass vaccination with a two-dose oral cholera vaccine in a refugee camp. Bull World Health Organ 77(10):837–842
Lindenbaum J, Greenough WB, Islam MR (1967) Antibiotic therapy of cholera. Bull World Health Organ 36(6):871–883
Lombardo MJ, Michalski J, Martinez-Wilson H, Morin C, Hilton T, Osorio CG, Nataro JP, Tacket CO, Camilli A, Kaper JB (2007) An in vivo expression technology screen for Vibrio cholerae genes expressed in human volunteers. Proc Natl Acad Sci USA 104(46):18229–18234. doi:10.1073/pnas.0705636104, 0705636104 [pii]
Matson JS, Withey JH, DiRita VJ (2007) Regulatory networks controlling Vibrio cholerae virulence gene expression. Infect Immun 75(12):5542–5549
Meibom KL, Blokesch M, Dolganov NA, Wu CY, Schoolnik GK (2005) Chitin induces natural competence in Vibrio cholerae. Science 310(5755):1824–1827. doi:10.1126/science.1120096
Merrell DS, Camilli A (2000) Detection and analysis of gene expression during infection by in vivo expression technology. Philos Trans R Soc Lond B Biol Sci 355(1397):587–599. doi:10.1098/rstb.2000.0600
Merrell DS, Butler SM, Qadri F, Dolganov NA, Alam A, Cohen MB, Calderwood SB, Schoolnik GK, Camilli A (2002) Host-induced epidemic spread of the cholera bacterium. Nature 417(6889):642–645. doi:10.1038/nature00778, nature00778 [pii]
Mosley WH, Bart KJ, Sommer A (1972) An epidemiological assessment of cholera control programs in rural East Pakistan. Int J Epidemiol 1(1):5–11
Na-Ubol M, Srimanote P, Chongsa-Nguan M, Indrawattana N, Sookrung N, Tapchaisri P, Yamazaki S, Bodhidatta L, Eampokalap B, Kurazono H, Hayashi H, Nair GB, Takeda Y, Chaicumpa W (2011) Hybrid & El Tor variant biotypes of Vibrio cholerae O1 in Thailand. Indian J Med Res 133(4):387–394
Piarroux R, Barrais R, Faucher B, Haus R, Piarroux M, Gaudart J, Magloire R, Raoult D (2011) Understanding the cholera epidemic, Haiti. Emerg Infect Dis 17(7):1161–1168. doi:10.3201/eid1707.110059
Pollitzer R (1954) Cholera studies. 1. History of the disease. Bull World Health Organ 10(3):421–461
Richard AL, Withey JH, Beyhan S, Yildiz F, DiRita VJ (2010) The Vibrio cholerae virulence regulatory cascade controls glucose uptake through activation of TarA, a small regulatory RNA. Mol Microbiol 78(5):1171–1181. doi:10.1111/j.1365-2958.2010.07397.x
Richie EE, Punjabi NH, Sidharta YY, Peetosutan KK, Sukandar MM, Wasserman SS, Lesmana MM, Wangsasaputra FF, Pandam SS, Levine MM, O’Hanley PP, Cryz SJ, Simanjuntak CH (2000) Efficacy trial of single-dose live oral cholera vaccine CVD 103-HgR in North Jakarta, Indonesia, a cholera-endemic area. Vaccine 18(22):2399–2410
Ritchie JM, Rui H, Bronson RT, Waldor MK (2010) Back to the future: studying cholera pathogenesis using infant rabbits. mBio 1(1). doi:10.1128/mBio.00047-10
Rodighiero C, Tsai B, Rapoport TA, Lencer WI (2002) Role of ubiquitination in retro-translocation of cholera toxin and escape of cytosolic degradation. EMBO Rep 3(12):1222–1227. doi:10.1093/embo-reports/kvf239
Rui H, Ritchie JM, Bronson RT, Mekalanos JJ, Zhang Y, Waldor MK (2010) Reactogenicity of live-attenuated Vibrio cholerae vaccines is dependent on flagellins. Proc Natl Acad Sci USA 107(9):4359–4364. doi:10.1073/pnas.0915164107, 0915164107 [pii]
Ryan ET, Calderwood SB, Qadri F (2006) Live attenuated oral cholera vaccines. Expert Rev Vaccines 5(4):483–494. doi:10.1586/14760584.5.4.483
Sack DA, Sack RB, Nair GB, Siddique AK (2004) Cholera. Lancet 363(9404):223–233
Schild S, Tamayo R, Nelson EJ, Qadri F, Calderwood SB, Camilli A (2007) Genes induced late in infection increase fitness of Vibrio cholerae after release into the environment. Cell Host Microbe 2(4):264–277. doi:10.1016/j.chom.2007.09.004, S1931-3128(07)00219-3 [pii]
Snow J (1855) On the mode of communication of cholera. John Churchill, London
Son MS, Megli CJ, Kovacikova G, Qadri F, Taylor RK (2011) Characterization of Vibrio cholerae O1 El Tor biotype variant clinical isolates from Bangladesh and Haiti, including a molecular genetic analysis of virulence genes. J Clin Microbiol 49(11):3739–3749. doi:10.1128/JCM.01286-11
Taviani E, Grim CJ, Choi J, Chun J, Haley B, Hasan NA, Huq A, Colwell RR (2010) Discovery of novel Vibrio cholerae VSP-II genomic islands using comparative genomic analysis. FEMS Microbiol Lett 308(2):130–137. doi:10.1111/j.1574-6968.2010.02008.x
Taylor RK, Miller VL, Furlong DB, Mekalanos JJ (1987) Use of phoA gene fusions to identify a pilus colonization factor coordinately regulated with cholera toxin. Proc Natl Acad Sci USA 84(9):2833–2837
Taylor DN, Killeen KP, Hack DC, Kenner JR, Coster TS, Beattie DT, Ezzell J, Hyman T, Trofa A, Sjogren MH et al (1994) Development of a live, oral, attenuated vaccine against El Tor cholera. J Infect Dis 170(6):1518–1523
Tickner J, Gouveia-Vigeant T (2005) The 1991 cholera epidemic in Peru: not a case of precaution gone awry. Risk Anal 25(3):495–502. doi:10.1111/j.1539-6924.2005.00617.x
Tsai B, Rodighiero C, Lencer WI, Rapoport TA (2001) Protein disulfide isomerase acts as a redox-dependent chaperone to unfold cholera toxin. Cell 104(6):937–948, S0092-8674(01)00289-6 [pii]
Waldor MK, Mekalanos JJ (1996) Lysogenic conversion by a filamentous phage encoding cholera toxin. Science 272(5270):1910–1914
WHO (2006) Implementing the new recommendations on the clinical management of diarrhoea. WHO Press, Geneva
WHO (2010) Updated WHO position paper on cholera vaccines. www.who.int/entity/immunization/cholera_PP_slides_20_Mar_2010.pdf
WHO (2011) Global epidemics and impact of cholera 2011. http://www.who.int/topics/cholera/impact/en/
Withey JH, DiRita VJ (2006) The toxbox: specific DNA sequence requirements for activation of Vibrio cholerae virulence genes by ToxT. Mol Microbiol 59(6):1779–1789
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Richard, A.L., DiRita, V.J. (2013). Cholera. In: Rosenberg, E., DeLong, E.F., Lory, S., Stackebrandt, E., Thompson, F. (eds) The Prokaryotes. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-30144-5_92
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DOI: https://doi.org/10.1007/978-3-642-30144-5_92
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