Evolution of new variants of Vibrio cholerae O1

doi:10.1016/j.tim.2009.10.003

Trends in Microbiology

Volume 18, Issue 1, January 2010, Pages 46-54

https://doi.org/10.1016/j.tim.2009.10.003 Get rights and content

Vibrio cholerae typically contains a prophage that carries the genes encoding the cholera toxin, which is responsible for the major clinical symptoms of the disease. In recent years, new pathogenic variants of V. cholerae have emerged and spread throughout many Asian and African countries. These variants display a mixture of phenotypic and genotypic traits from the two main biotypes (known as ‘classical’ and ‘El Tor’), suggesting that they are genetic hybrids. Classical and El Tor biotypes have been the most epidemiologically successful cholera strains during the past century, and it is believed that the new variants (which we call here ‘atypical El Tor’) are likely to develop successfully in a manner similar to these biotypes. Here, we describe recent advances in our understanding of the epidemiology and evolution of the atypical El Tor strains.

Section snippets

Vibrio cholerae subtypes and their epidemiology

Cholera, a severe form of acute secretory diarrhoea, is caused by the gamma-proteobacterium Vibrio cholerae. Pathogenic strains harbour a cholera toxin prophage (CTXΦ) that carries the genes that encode the cholera toxin (CT), a key virulence factor that is directly responsible for the major clinical symptoms of the disease [1]. CT binds to a specific receptor (GM₁) on host enterocytes and is internalized, leading to elevated intracellular cAMP levels and resulting in a major loss of water and

Cholera phage and toxin in V. cholerae biotypes

CTXΦ carried by toxigenic V. cholerae strains consists of two functionally distinct gene clusters, namely, the core and the RS2 region (Figure 2a)[35]. The core region includes the ctxAB genes, encoding CT, together with five other genes encoding Psh, Core-encoded pilin (Cep), pIII^CTX, Accessory cholera enterotoxin (Ace) and Zonula occludens (Zot), which are required for phage morphogenesis. The RS2 region encodes proteins with roles in the replication (RstA), integration (RstB) and regulation

Atypical El Tor strains

Classical and El Tor biotypes, therefore, have different phenotypic and genotypic properties (Table 1). However, V. cholerae O1 strains exist that cannot be classified into any of the two biotypes based on the mentioned traits. Here, we use the term ‘atypical El Tor’ for these unusual strains, which appear to have a mix of both classical and El Tor traits. Several atypical El Tor strains have been recently identified and reported in the literature, and these are briefly described below.

Epidemiology of classical strains and the evolution of atypical El Tor strains

Since the beginning of the seventh pandemic, El Tor strains have gradually displaced the classical strains as the cause of cholera. In Bangladesh, the classical biotype apparently disappeared in 1973, but re-emerged in 1982 60, 61 and co-circulated with the El Tor biotype for at least a decade (the last isolation was reported in 1992) [61]. Curiously, the transient reappearance of O1 classical strains was observed only in Bangladesh.

Classical strains are now believed to be extinct; hence, the

Possible hosts for CTXΦ^Cla in the origin of atypical El Tor strains

We do not know which Vibrio strains acted as hosts in the origin of atypical El Tor strains. Whereas the seventh pandemic El Tor clone is thought to have reached Bangladesh during the late 1970 s, it is commonly believed that it has never reached the USA [1]. Hence, the seventh pandemic El Tor clone is an unlikely host in the origination of the US Gulf Coast El Tor strains. However, it might have served as the host for the emergence of the current atypical El Tor strains that first appeared in

Nomenclature and identification of atypical El Tor strains: problems and solutions

Although there is ongoing speculation regarding the origins of the different atypical El Tor variants, it seems clear that these strains are more similar to El Tor strains, despite having some classical traits. In particular, the classical rstR^Cla and ctxB1 alleles are consistently seen in most atypical El Tor strains 30, 31, 32, 33. For these reasons, we propose that ‘atypical El Tor’ is used as a broad term to describe all V. cholerae O1 El Tor strains that harbour classical traits.

Since the

Concluding remarks and future directions

The evolution and continuing emergence of new pathogenic variants of V. cholerae over the past 100 years have posed major challenges to governments that attempt to control and manage this highly infectious disease. Recent investigations of the new variants have provided clues that are helping researchers to understand the probable origin of pathogenic variants from non-pathogenic ancestors and the natural events that might have contributed to their improved evolutionary fitness 56, 68, 74, 75,

Acknowledgements

We thank the anonymous reviewers for their insight and helpful comments. The work of R.Y.C.K. and A.S. is funded by an Area of Excellence Grant from the University Grants Committee of the Hong Kong Special Administrative Region, China (AoE/P-04/04). The work of G.B.N. is supported by the Indian Council of Medical Research.

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Trends in Microbiology

ReviewEvolution of new variants of Vibrio cholerae O1

Section snippets

Vibrio cholerae subtypes and their epidemiology

Cholera phage and toxin in V. cholerae biotypes

Atypical El Tor strains

Epidemiology of classical strains and the evolution of atypical El Tor strains

Possible hosts for CTXΦCla in the origin of atypical El Tor strains

Nomenclature and identification of atypical El Tor strains: problems and solutions

Concluding remarks and future directions

Acknowledgements

Gene

Lancet

Gene

Lancet

J. Infect.

Lancet

Curr. Opin. Microbiol.

Lancet

Lancet

Trends. Microbiol.

Trends. Microbiol.

Lancet

Diagn. Microbiol. Infect. Dis.

Cholera

Clin. Microbiol. Rev

Vibrio cholerae: cholera toxin

Int. J. Biochem. Cell Biol.

Isolation and identification of Vibrio cholerae O1 from fecal specimens

Manual for Laboratory Investigations of Acute Enteric Infections

Use of automated sequencing of polymerase chain reaction-generated amplicons to identify three types of cholera toxin subunit B in Vibrio cholerae O1 strains

J. Clin. Microbiol.

CTXΦ immunity: application in the development of cholera vaccines

Proc. Natl. Acad. Sci. U. S. A.

Epitopes of the cholera family of enterotoxins

Rev. Infect. Dis.

Evolutionary genetic analysis of the emergence of epidemic Vibrio cholerae isolates on the basis of comparative nucleotide sequence analysis and multilocus virulence gene profiles

J. Clin. Microbiol.

Detection of RTX toxin gene in Vibrio cholerae by PCR

J. Clin. Microbiol.

Comparative genomic analysis of Vibrio cholerae: genes that correlate with cholera endemic and pandemic disease

Proc. Natl. Acad. Sci. U. S. A.

Identification of a Vibrio cholerae RTX toxin gene cluster that is tightly linked to the cholera toxin prophage

Proc. Natl. Acad. Sci. U. S. A.

Cholera

Isolation of nonagglutinable vibrios from an enteritis outbreak in Czechoslovakia

J. Infect. Dis.

Outbreak of gastroenteritis by nonagglutinable (NAG) vibrios in the Republic of Sudan

J. Egypt. Public Health Assoc.

Cholera – a possible endemic focus in the United States

N. Engl. J. Med.

Endemic cholera in Australia and the United States

Outbreak of Vibrio cholerae non-O1 in India and Bangladesh

Lancet

Vibrio cholerae O139 and epidemic cholera

Commun. Dis. Rep. Weekly

Imported cholera associated with a newly described toxigenic Vibrio cholerae O139 strain-California

Morbid. Mortal. Weekly Rep.

Vibrio cholerae O139: how great is the threat of a pandemic?

Trop. Med. Int. Health

Vibrio cholerae non-O1 - the eighth pandemic?

Lancet

Genetic rearrangements in the rfb regions of Vibrio cholerae O1 and O139

Proc. Natl. Acad. Sci. U. S. A.

Genesis of the novel epidemic Vibrio cholerae O139 strain: evidence for horizontal transfer of genes involved in polysaccharide synthesis

EMBO J.

DNA fingerprinting of Vibrio cholerae strains with a novel insertion sequence element: a tool to identify epidemic strains

J. Clin. Microbiol.

Molecular analysis of rRNA and cholera toxin genes carried by the new epidemic strain of toxigenic Vibrio cholerae O139 synonym Bengal

J. Clin. Microbiol.

New variants of Vibrio cholerae O1 biotype El Tor with attributes of the classical biotype from hospitalized patients with acute diarrhea in Bangladesh

J. Clin. Microbiol.

Cholera in Mozambique, variant of Vibrio cholerae

Emerg. Infect. Dis.

Cholera due to altered El Tor strains of Vibrio cholerae O1 in Bangladesh

J. Clin. Microbiol.

Vibrio cholerae O1 hybrid El Tor strains, Asia and Africa

Emerg. Infect. Dis

Epidemiology, genetics, and ecology of toxigenic Vibrio cholerae

Microbiol. Mol. Biol. Rev.

Review
Evolution of new variants of Vibrio cholerae O1

Possible hosts for CTXΦ^Cla in the origin of atypical El Tor strains