Regulation of sialic acid transport and catabolism in Haemophilus influenzae.
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.
Johnston
Jason W
JW
Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA.
Zaleski
Anthony
A
Allen
Simon
S
Mootz
Joe M
JM
Armbruster
David
D
Gibson
Bradford W
BW
Apicella
Michael A
MA
Munson
Robert S
RS
D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology; D001692:Biological Transport; D001770:Blood Bactericidal Activity; D015169:Colony Count, Microbial; D002373:Cyclic AMP Receptor Protein / Q000502:physiology; D018983:DNA Footprinting; D004269:DNA, Bacterial / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D017353:Gene Deletion; D005786:Gene Expression Regulation; D015964:Gene Expression Regulation, Bacterial; D006193:Haemophilus influenzae / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000737:chemistry / Q000302:isolation & purification; D016254:Mutagenesis, Insertional; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D011485:Protein Binding; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D001426:Bacterial Proteins; D002373:Cyclic AMP Receptor Protein; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D008070:Lipopolysaccharides; D012097:Repressor Proteins; D014157:Transcription Factors; C023023:lipid-linked oligosaccharides; D019158:N-Acetylneuraminic Acid