Expression of Vibrio cholerae virulence genes in response to environmental signals.
Vibrio cholerae, the causative agent of Asiatic cholera, is a gram-negative motile bacterial species acquired via oral ingestion of contaminated food or water sources. The O1 serogroup of V. cholerae is responsible for pandemic cholera and is divided into two biotypes, classical and El Tor (Butterton and Calderwood, 1995; Mekalanos, 1985). The El Tor biotype is responsible for the current cholera pandemic. In the absence of disease, the vibrio life cycle consists of a free-swimming phase in marine and estuarine environments in association with zooplankton, crustaceans, insects, and water plants. Vibrios interact with various surfaces found in the environment to generate biofilms which may promote survival (Watnick etaL, 1999). Within the host the motile vibrios must evade the innate host defense mechanisms, penetrate the mucus layer covering the intestinal villi, adhere to and colonize the epithelial surface of the small intestine, assume a non-motile phase, replicate and cause disease by secreting numerous exoproteins at the site of infection (Oliver and Kaper, 1997). The voluminous diarrhea associated with cholera infection leads to the dissemination of the vibrios back into a watery environment and thus a continuation of the environmental phase of the life cycle. The host phase of the vibrio life cycle is only possible through the action of a group of virulence genes (ToxR-regulon) controlled by a complex and incompletely understood regulatory cascade. The ToxR regulon colonization and toxin genes are coordinately expressed in response to specific host signals that have yet to be completely defined (Skorupsky and Taylor 1997). Although little is known regarding the host signals that impact the ToxR regulatory cascade, it is clear that these intraintestinal signals play an important role in maximizing the ability of the vibrios to survive and multiply within the host. Key to understanding the complex events involved in the pathogenesis of V. cholerae will be elucidating the intraintestinal signaling molecules that trigger the expression of vibrio virulence genes. Understanding the molecular basis of this host-parasite interaction will provide important information with respect to how pathogenic bacteria establish infection and provide insights leading to novel methods for treating and/or preventing bacterial infections. This review will summarize what is known regarding host signaling and the complex ToxR regulatory system employed by V. cholerae to coordinate virulence gene expression within the host.
Peterson
Kenneth M
KM
Louisiana State University Health Sciences Center, Department of Microbiology and Immunology, Shreveport, Louisiana 71130, USA. kpeter@lsuhsc.edu
D001426:Bacterial Proteins; D002771:Cholera / Q000382:microbiology; D002772:Cholera Toxin / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D010861:Fimbriae, Bacterial / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D018085:Regulon; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014734:Vibrio cholerae / Q000235:genetics* / Q000472:pathogenicity*; D014774:Virulence / Q000235:genetics
D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D014157:Transcription Factors; C499324:toxR protein, Vibrio cholerae; C066719:toxR protein, bacteria; D002772:Cholera Toxin