Search

A subset of non-Ol/non-O139 serogroup strains of Vibrio cholerae cause disease using type 3 secretion system (T3SS)-mediated mechanisms. An ~50-kb genomic island carries genes encoding the T3SS structural apparatus, effector proteins, and two trans-membrane transcriptional regulators, VttRA and VttRB, which are ToxR homologues. Previous experiments demonstrated that VttRA and VttRB are necessary for colonization in vivo and promote bile-dependent T3SS gene expression in vitro. To better understand the scope of genes that are potential targets of VttRA and VttRB regulation, we performed deep RNA sequencing using 039 serogroup strain AM-19226 and derivatives carrying deletions in vttRA and vttRB grown in bile. Comparison of the transcript profiles from AvttRA and \vttRB mutant strains to the isogenic parent strain confirmed that VttRA and VttRB regulate expression of some T3SS island genes and provided additional information about relative expression levels and operon organization. Interestingly, the data also suggested that additional genes, located outside the T3SS island and encoding functions involved in motility, chemotaxis, type 6 secretion, transcriptional regulation, and stress responses, may also by regulated by VttRA and VttRB. We verified transcript levels for selected genes by quantitative reverse transcription (RT)-PCR and then focused additional studies on motility and biofilm formation. The results suggest that VttRA and VttRB act as part of a complex transcriptional network that coordinates virulence gene expression with multiple cellular phenotypes. VttRA and VttRB therefore represent horizontally acquired transcriptional regulators with the ability to influence global gene expression in addition to modulating gene expression within the T3SS genomic island. [ABSTRACT FROM AUTHOR]

Non-O1, non-O139 Vibrio cholerae can cause gastroenteritis and extraintestinal infections, but, unlike 01 and 0139 strains of V. cholerae, little is known about the virulence gene content of non-O1, non-0139 strains and their phylogenetic relationship to other pathogenic V. cholerae. Comparative genomic microarray analysis of four pathogenic non-O1, non-0139 strains indicates that these strains are quite divergent from O1 and 0139 strains. Genomic sequence analysis of a non-O1, non-0139 strain (AM- 19226) that appeared particularly pathogenic in experimental animals suggests that this strain carries a type III secretion system (1755) that is related to the 17552 gene cluster found in a pandemic clone of Vibrio parahaemolyticus. The genes for this V. cholerae TTSS system appear to be present in many clinical and environ- mental non-O1, non-O139 strains, including at least one clone that is globally distributed. We hypothesize that the 1755 present in some pathogenic strains of non-O1, non-O139 V. cho!erae may be involved in the virulence and environmental fitness of these strains. [ABSTRACT FROM AUTHOR]