1887

Abstract

The toxin-coregulated pilus (TCP) is a critical determinant of the pathogenicity of . This bundle-forming pilus is an essential intestinal colonization factor and also serves as a receptor for CTXϕ, the filamentous phage that encodes cholera toxin (CT). TCP is a polymer of repeating subunits of the major pilin protein TcpA and is found within the pathogenicity island (VPI). In this study genetic variation at the locus in toxigenic isolates of was investigated and three novel TcpA sequences from strains V46, V52 and V54, belonging to serogroups O141, O37 and O8, respectively, were identified. These novel alleles grouped into three distinct clonal lineages. The polymorphisms in TcpA were predominantly located in the carboxyl region of TcpA in surface-exposed regions of TCP fibres. Comparison of the genetic diversity among isolates at the locus with that of , another locus within the VPI, and , a chromosomal locus, revealed that sequences are far more diverse than these other loci. Most likely, this diversity is a reflection of diversifying selection in adaptation to the host immune response or to CTXϕ susceptibility. An assessment of the functional properties of the variant sequences in the non-O1 strains was carried out by analysing whether these strains could be infected by CTXϕ and colonize the suckling mouse. Similar to El Tor strains of . O1, CTXϕ infection of these strains required the exogenous expression of , suggesting that in these strains ToxT regulates TCP expression and that these TcpA variants can serve as CTXϕ receptors. All the non-O1 serogroup isolates tested were capable of colonizing the suckling mouse small intestine, suggesting that the different TcpA variants could function as colonization factors.

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2002-06-01
2019-08-19
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