Moraxella catarrhalis binds plasminogen to evade host innate immunity.

• Several bacterial species recruit the complement regulators C4b binding protein, Factor H and vitronectin resulting in resistance against the bactericidal activity of human serum. It has recently been demonstrated that bacteria also bind plasminogen, which is converted to plasmin that degrades C3b and C5. In this study, we found that a series of clinical isolates (n=58) of the respiratory pathogen M. catarrhalis, which is commonly isolated from pre-school children and adults with chronic obstructive pulmonary disease (COPD), significantly binds human plasminogen. Ubiquitous surface protein (Usp) A2 and A2 hybrid (UspA2H) was identified as the plasminogen-binding factor in the outer membrane proteome of Moraxella. Furthermore, expression of a series of truncated recombinant UspA2 and UspA2H followed by a detailed analysis of protein-protein interactions suggested that the N-terminal head domains bound to the kringle domains of plasminogen. The binding affinity constant (KD) for UspA2(30-539) and UspA2H(50-720) to immobilized plasminogen was 4.8x10(-8) M and 3.13x10(-8) M, respectively, as measured by Biolayer inferometry. Plasminogen bound to intact M. catarrhalis or to recombinant UspA2/A2H was readily accessible for urokinase plasminogen activator that converted the zymogen into active plasmin as verified by the specific substrate S-2251, and a degradation assay comprising fibrinogen. Importantly, plasmin bound at the bacterial surface also degraded C3b and C5 that consequently may contribute to a reduced bacterial killing. Our findings suggest that binding of plasminogen to M. catarrhalis may lead to increased virulence and hence more efficient colonization of the host.

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MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Microbiology in the medical area (hsv//eng)

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