Department of Microbiology and Physiological Systems; Department of Medicine, Division of Infectious Diseases and Immunology
Adolescent; Adult; Aged; Antibodies, Bacterial; Bacterial Outer Membrane Proteins; *Blood Bactericidal Activity; Complement Pathway, Alternative; Complement Pathway, Classical; Complement System Proteins; Haemophilus influenzae; Humans; Immunoglobulin M; *Microbial Viability; Middle Aged; Protein Binding; Young Adult
Immunity | Immunology of Infectious Disease | Immunopathology | Virology
The complement system is an important first line of defense against the human pathogen Haemophilus influenzae. To survive and propagate in vivo, H. influenzae has evolved mechanisms for subverting this host defense, most of which have been shown to involve outer surface structures, including lipooligosaccharide glycans and outer surface proteins. Bacterial defense against complement acts at multiple steps in the pathway by mechanisms that are not fully understood. Here we identify outer membrane protein P5 as an essential factor in serum resistance of both H. influenzae strain Rd and nontypeable H. influenzae (NTHi) clinical isolate NT127. P5 was essential for resistance of Rd and NT127 to complement in pooled human serum. Further investigation determined that P5 expression decreased cell surface binding of IgM, a potent activator of the classical pathway of complement, to both Rd and NT127. Additionally, P5 expression was required for NT127 to bind factor H (fH), an important inhibitor of alternative pathway (AP) activation. Collectively, the results obtained in this work highlight the ability of H. influenzae to utilize a single protein to perform multiple protective functions for evading host immunity.
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Copyright © 2014, American Society for Microbiology. Publisher PDF posted as allowed by the publisher's author rights policy at http://journals.asm.org/site/misc/ASM_Author_Statement.xhtml.
DOI of Published Version
Infect Immun. 2014 Feb;82(2):640-9. doi: 10.1128/IAI.01224-13. Epub 2013 Nov 25. Link to article on publisher's site
Infection and immunity
Rosadini, Charles V.; Ram, Sanjay; and Akerley, Brian J., "Outer membrane protein P5 is required for resistance of nontypeable Haemophilus influenzae to both the classical and alternative complement pathways" (2014). University of Massachusetts Medical School Faculty Publications. 801.