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Open Access Research article

Sialic acid transport and catabolism are cooperatively regulated by SiaR and CRP in nontypeable Haemophilus influenzae

Jason W Johnston1*, Haider Shamsulddin2, Anne-Frances Miller2 and Michael A Apicella3

Author Affiliations

1 Department of Microbiology, Immunology, and Molecular Genetics, The University of Kentucky, Lexington, KY, USA

2 Department of Chemistry, The University of Kentucky, Lexington, KY, USA

3 Department of Microbiology, The University of Iowa, Iowa City, IA, USA

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BMC Microbiology 2010, 10:240  doi:10.1186/1471-2180-10-240

Published: 15 September 2010

Abstract

Background

The transport and catabolism of sialic acid, a critical virulence factor for nontypeable Haemophilus influenzae, is regulated by two transcription factors, SiaR and CRP.

Results

Using a mutagenesis approach, glucosamine-6-phosphate (GlcN-6P) was identified as a co-activator for SiaR. Evidence for the cooperative regulation of both the sialic acid catabolic and transport operons suggested that cooperativity between SiaR and CRP is required for regulation. cAMP was unable to influence the expression of the catabolic operon in the absence of SiaR but was able to induce catabolic operon expression when both SiaR and GlcN-6P were present. Alteration of helical phasing supported this observation by uncoupling SiaR and CRP regulation. The insertion of one half-turn of DNA between the SiaR and CRP operators resulted in the loss of SiaR-mediated repression of the transport operon while eliminating cAMP-dependent induction of the catabolic operon when GlcN-6P was present. SiaR and CRP were found to bind to their respective operators simultaneously and GlcN-6P altered the interaction of SiaR with its operator.

Conclusions

These results suggest multiple novel features for the regulation of these two adjacent operons. SiaR functions as both a repressor and an activator and SiaR and CRP interact to regulate both operons from a single set of operators.