Binding of human factor H to outer membrane protein P 5 of non‐typeable H aemophilus influenzae contributes to complement resistance

Summary Non‐typeable H aemophilus influenzae is an opportunistic pathogen of the human upper respiratory tract and is often found to cause inflammatory diseases that include sinusitis, otitis media and exacerbations of chronic obstructive pulmonary disease. To persist in the inflammatory milieu during infection, non‐typeable H . influenzae must resist the antimicrobial activity of the human complement system. Here, we used Tn ‐seq to identify genes important for resistance to complement‐mediated killing. This screen identified outer membrane protein P 5 in evasion of the alternative pathway of complement activation. Outer membrane protein P 5 was shown to bind human complement regulatory protein factor H directly, thereby, preventing complement factor C 3 deposition on the surface of the bacterium. Furthermore, we show that amino acid variation within surface‐exposed regions within outer membrane P 5 affected the level of factor H binding between individual strains.