Comparative genomic analysis of Vibrio cholerae O31: capsule, O-antigen, pathogenesis and genome
Morris, J Glenn
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Vibrio cholerae is the causative agent of cholera. In order to understand the genetic basis underlying the emergence of novel epidemic strains of V. cholerae, the genetics of surface polysaccharide biogenesis, and the role of lateral gene transfer in the evolution of this species, we investigated. NRT36S and A5 are both NAG-ST producing, cholera toxin negative, serogroup O31 V. cholerae. NRT36S is encapsulated and causes diarrhea when administered to volunteers; A5 is acapsular and does not colonize or cause illness in humans. The structure of the capsular (CPS) polysaccharide in NRT36S was determined by NMR. The gene cluster of CPS biogenesis was identified by transposon mutagenesis combined with whole genome sequencing data. The CPS gene cluster shared the same genetic locus as that of the O-antigen of lipopolysaccharide (LPS) biogenesis gene cluster. The LPS biogenesis regions in A5 were similar to NRT36S except that a 6.5 kb fragment in A5 replaced a 10 kb fragment in NRT36S in the middle of the LPS gene cluster. The genome of NRT36S was sequenced to a draft containing 174 contigs plus the superintegron region. Besides confirming the existence of NAG-ST, we also identified the genes for a type three secretion system (TTSS), a putative exotoxin, and two different RTX genes. Four pili systems were also identified. Therefore, the genome of non-O1 Vibrio cholerae NRT36S demonstrates the presence of pathogenic mechanisms that are distinct from O1 V. cholerae. We conclude that lateral gene transfer plays a critical role in the emergence of new strains. The co-location of CPS and LPS could provide a mechanism for simultaneous emergence of new O and K antigens in a single strain. Our data also highlights the apparent mobility within the CPS/LPS region that would provide a basis for the large number of observed V. cholerae serogroups and the emergence of novel epidemic strains.