Department of Microbiology and Physiological Systems; Department of Medicine, Division of Infectious Diseases and Immunology
Medical Subject Headings
Animals; Bacterial Proteins; Blotting, Western; Cell Separation; Complement System Proteins; Flow Cytometry; Gene Expression; Gene Expression Profiling; Gene Expression Regulation, Bacterial; Haemophilus Infections; Haemophilus influenzae; Humans; Immune Evasion; Lipopolysaccharides; Mice; Oxidation-Reduction; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction
Immunology and Infectious Disease | Microbiology | Physiology
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.
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Citation: Infect Immun. 2011 May;79(5):1971-83. Epub 2011 Feb 28. Link to article on publisher's site