Moraxella catarrhalis binds plasminogen to evade host innate immunity.

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Abstract

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.

Detaljer

Författare
Enheter & grupper
Externa organisationer
  • Leibniz Institute for Natural Product Research and Infection Biology
  • Friedrich Schiller University Jena
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Mikrobiologi inom det medicinska området
Originalspråkengelska
Sidor (från-till)3458-3469
TidskriftInfection and Immunity
Volym83
Utgåva nummer9
StatusPublished - 2015
PublikationskategoriForskning
Peer review utfördJa

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