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Regulation of sialic acid transport and catabolism in Haemophilus influenzae
Author(s) -
Johnston Jason W.,
Zaleski Anthony,
Allen Simon,
Mootz Joe M.,
Armbruster David,
Gibson Bradford W.,
Apicella Michael A.,
Munson Robert S.
Publication year - 2007
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2007.05890.x
Subject(s) - operon , sialic acid , biology , catabolism , haemophilus influenzae , biochemistry , repressor , microbiology and biotechnology , gene , escherichia coli , metabolism , gene expression , antibiotics
Summary Virulence of nontypeable Haemophilus influenzae (NTHi) is dependent on the decoration of lipooligosaccharide with sialic acid. This sugar must be derived from the host, as NTHi cannot synthesize sialic acids. NTHi can also use sialic acid as a carbon source. The genes encoding the sialic acid transporter and the genes encoding the catabolic activities are localized to two divergently transcribed operons, the siaPT operon and the nan operon respectively. In this study, we identified SiaR as a repressor of sialic acid transport and catabolism in NTHi. Inactivation of siaR resulted in the unregulated expression of the genes in both operons. Unregulated catabolism of sialic acid in the siaR mutant resulted in the reduction of surface sialylation and an increase in serum sensitivity. In addition to SiaR‐mediated repression, CRP, the cAMP receptor protein, was shown to activate expression of the siaPT operon but not the nan operon. We describe a model in which SiaR and CRP work to modulate intracellular sialic acid levels. Our results demonstrate the importance of SiaR‐mediated regulation to balance the requirement of surface sialylation and the toxic accumulation of intracellular sialic acid.