Moraxella catarrhalis binds plasminogen to evade host innate immunity.
Author
Summary, in English
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.
Department/s
Publishing year
2015
Language
English
Pages
3458-3469
Publication/Series
Infection and Immunity
Volume
83
Issue
9
Full text
Links
Document type
Journal article
Publisher
American Society for Microbiology
Topic
- Microbiology in the medical area
Status
Published
Research group
- Clinical Microbiology, Malmö
ISBN/ISSN/Other
- ISSN: 1098-5522