All ETDs from UAB

Advisory Committee Chair

Moon H Nahm

Advisory Committee Members

William H Benjamin

David E Briles

Susan K Hollingshead

David G Pritchard

Hui Wu

Document Type

Dissertation

Date of Award

2010

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

Serogroup 6 of Streptococcus pneumoniae has been known to contain three serotypes, named 6A, 6B and 6C, with highly homologous capsule gene loci. The 6A and 6B capsule gene loci consistently differ from each other by only one nucleotide in the wciP gene. The 6A capsule gene locus has a galactosyltransferase (wciNα), which has been replaced with a glucosyltransferase (wciNß) in the 6C capsule gene locus. We considered that a new serotype, 6D, would be possible if the glucosyltransferase found in 6C strains was combined with the wciP gene from a 6B strain. We demonstrate that this gene combination yields a viable pneumococcal strain and that the capsular polysaccharide (PS) from this strain has the predicted chemical structure and serological similarity to the capsular PS of the 6B serotype. The new 6D serotype can be distinguished from serotype 6B strains with a set of mAbs, and by using these mAbs, we were able to discover two 6D isolates obtained from Korea. Therefore, the novel 6D serotype is structurally unique and clinically relevant. After the discovery of 6C and the novel 6D, it became necessary to reexamine the evolution relationship of serogroup 6. In addition to supporting the conclusions from previous studies, the results presented in this study have allowed us to build a hypothetical model for serogroup 6 evolution. By analyzing sequences of a diverse set of 6C strains, we hypothesize that the cps loci from all these strains have a single origin, due to their low level of diversity. While the source of the foreign gene incorporated into a serogroup 6 strain to create 6C is still unknown, our results provide evidence that the source of this gene in 6D was from a 6C strain. Furthermore, through MLST analysis we have examined the mechanism of the well-documented expansion of serotype 6C post common use of the PCV-7 vaccine.

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