ArcA-Regulated Glycosyltransferase Lic2B Promotes Complement Evasion and Pathogenesis of Nontypeable Haemophilus influenzae

Abstract

ABSTRACTSignaling mechanisms used byHaemophilus influenzaeto 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 byH. influenzae. We show that ArcA of nontypeableH. influenzae(NTHI) activates expression of a glycosyltransferase gene,lic2B.Structural comparison of the lipooligosaccharide (LOS) of alic2Bmutant to that of the wild-type strain NT127 revealed thatlic2Bis required for addition of a galactose residue to the LOS outer core. Thelic2Bgene 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.