A conserved UDP-glucose dehydrogenase encoded outside the hasABC operon contributes to capsule biogenesis in group A Streptococcus

Cole, Jason N., Aziz, Ramy K., Kuipers, Kirsten, Timmer, Anjuli M., Nizet, Victor and van Sorge, Nina M. (2012) A conserved UDP-glucose dehydrogenase encoded outside the hasABC operon contributes to capsule biogenesis in group A Streptococcus. Journal of Bacteriology, 194 22: 6154-6161. doi:10.1128/JB.01317-12

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Author Cole, Jason N.
Aziz, Ramy K.
Kuipers, Kirsten
Timmer, Anjuli M.
Nizet, Victor
van Sorge, Nina M.
Title A conserved UDP-glucose dehydrogenase encoded outside the hasABC operon contributes to capsule biogenesis in group A Streptococcus
Formatted title
A conserved UDP-glucose dehydrogenase encoded outside the hasABC operon contributes to capsule biogenesis in Group A Streptococcus
Journal name Journal of Bacteriology   Check publisher's open access policy
ISSN 0021-9193
1098-5530
Publication date 2012-11-01
Sub-type Article (original research)
DOI 10.1128/JB.01317-12
Open Access Status File (Publisher version)
Volume 194
Issue 22
Start page 6154
End page 6161
Total pages 8
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Language eng
Abstract Group A Streptococcus (GAS) is a human-specific bacterial pathogen responsible for serious morbidity and mortality worldwide. The hyaluronic acid (HA) capsule of GAS is a major virulence factor, contributing to bloodstream survival through resistance toneutrophil and antimicrobial peptide killing and to in vivo pathogenicity. Capsule biosynthesis has been exclusively attributedto the ubiquitous hasABC hyaluronan synthase operon, which is highly conserved across GAS serotypes. Previous reports indicatethat hasA, encoding hyaluronan synthase, and hasB, encoding UDP-glucose 6-dehydrogenase, are essential for capsule productionin GAS. Here, we report that precise allelic exchange mutagenesis of hasB in GAS strain 5448, a representative of theglobally disseminated M1T1 serotype, did not abolish HA capsule synthesis. In silico whole-genome screening identified a putativeHasB paralog, designated HasB2, with 45% amino acid identity to HasB at a distant location in the GAS chromosome. Invitro enzymatic assays demonstrated that recombinant HasB2 is a functional UDP-glucose 6-dehydrogenase enzyme. Mutagenesisof hasB2 alone slightly decreased capsule abundance; however, a ΔhasB ΔhasB2 double mutant became completely acapsular. We conclude that HasB is not essential for M1T1 GAS capsule biogenesis due to the presence of a newly identified HasB paralog,HasB2, which most likely resulted from gene duplication. The identification of redundant UDP-glucose 6-dehydrogenases underscoresthe importance of HA capsule expression for M1T1 GAS pathogenicity and survival in the human host.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published ahead of print: 7 September 2012.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Chemistry and Molecular Biosciences
 
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Created: Fri, 07 Dec 2012, 19:34:41 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences