title: ArcA-regulated glycosyltransferase lic2B promotes complement evasion and pathogenesis of nontypeable Haemophilus influenzae.
abstract: Signaling mechanisms used by Haemophilus influenzae to adapt to conditions it encounters during stages of infection and pathogenesis are not well understood. The ArcAB two-component signal transduction system controls gene expression in response to respiratory conditions of growth and contributes to resistance to bactericidal effects of serum and to bloodstream infection by H. influenzae. We show that ArcA of nontypeable H. influenzae (NTHI) activates expression of a glycosyltransferase gene, lic2B. Structural comparison of the lipooligosaccharide (LOS) of a lic2B mutant to that of the wild-type strain NT127 revealed that lic2B is required for addition of a galactose residue to the LOS outer core. The lic2B gene was crucial for optimal survival of NTHI in a mouse model of bacteremia and for evasion of serum complement. The results demonstrate that ArcA, which controls cellular metabolism in response to environmental reduction and oxidation (redox) conditions, also coordinately controls genes that are critical for immune evasion, providing evidence that NTHI integrates redox signals to regulate specific countermeasures against host defense.
authors.affiliation: Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, 55 Lake Ave. N., S6-242, Worcester, MA 01655, USA.
authors.forename: Sandy M S
authors.initials: SM
authors.lastname: Wong
authors.forename: Frank
authors.initials: F
authors.lastname: St Michael
authors.forename: Andrew
authors.initials: A
authors.lastname: Cox
authors.forename: Sanjay
authors.initials: S
authors.lastname: Ram
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Akerley
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D015153:Blotting, Western; D002469:Cell Separation; D003165:Complement System Proteins / Q000276:immunology*; D005434:Flow Cytometry; D015870:Gene Expression; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D006192:Haemophilus Infections / Q000276:immunology*; D006193:Haemophilus influenzae / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D006801:Humans; D057131:Immune Evasion / Q000235:genetics*; D008070:Lipopolysaccharides / Q000737:chemistry / Q000276:immunology; D051379:Mice; D010084:Oxidation-Reduction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; D008070:Lipopolysaccharides; C104912:lic2B protein, Haemophilus influenzae; C023023:lipid-linked oligosaccharides; D003165:Complement System Proteins