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Evolution of the Hyaluronic Acid Synthesis (has) Operon in Streptococcus zooepidemicus and Other Pathogenic Streptococci

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Hyaluronic acid (HA) is a ubiquitous linear polysaccharide in vertebrates and also is the capsule material of some pathogenic bacteria including group A and C streptococci. In bacteria, the HA synthase occurs in an operon (has) coding for enzymes involved in the production of HA precursors. We report two new members of the has operon family from Streptococcus equi subsp. zooepidemicus (S. zooepidemicus) and Streptococcus equi subsp. equi (S. equi). The has operon of S. zooepidemicus contains, in order, hasA, hasB, hasC, glum, and pgi, whereas these genes are separated on two operons in S. equi (hasA, hasB, hasC and hasC, glmU, pgi). The transcription start site and a σ70 promoter were experimentally identified 50 bp upstream of hasA in S. zooepidemicus. We performed a phylogenetic analysis of each of the has operon genes to determine the evolutionary origin(s) of the streptococcal has operon. In contrast to other capsular and exopolysaccharide operons, has operons have undergone no detectable interspecies lateral gene transfers in their construction, instead relying on intragenome gene duplication for their assembly. Specifically, hasC and glmU appear to have been duplicated into the S. zooepidemicus has operon from remotely located but near-identical paralogues most likely to improve HA productivity by gene dosage in this streptococcus. The intragene rearrangements appear to be ongoing events and the two has operons of the S. equi subspecies represent two alternatives of the same gene arrangement. A scenario for the evolution of streptococcal has operons is proposed.

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hasA :

Hyaluronate synthase

hasB :

UDP-glucose dehydrogenase

hasC :

glucose-1-phosphate uridyltransferase

glmU :

N-acetyl-glucosamine-1-phosphate uridyltransferase

pgi :

glucose-6-phosphate isomerase


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This work was supported by Grant A89937110 from the Australian Research Council.

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Correspondence to Lars M. Blank.

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Blank, L.M., Hugenholtz, P. & Nielsen, L.K. Evolution of the Hyaluronic Acid Synthesis (has) Operon in Streptococcus zooepidemicus and Other Pathogenic Streptococci. J Mol Evol 67, 13–22 (2008).

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