BBA70 of Borrelia burgdorferi Is a Novel Plasminogen-binding Protein

Koenigs, Arno; Hammerschmidt, Claudia; Jutras, Brandon L.; Pogoryelov, Denys; Barthel, Diana; Skerka, Christine; Kugelstadt, Dominik; Wallich, Reinhard; Stevenson, Brian; Zipfel, Peter F.; Kraiczy, Peter

doi:10.1074/jbc.m112.413872

Cited by 59 publications

(69 citation statements)

References 90 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was previously shown that plasminogen bound at the surface of cells of the respiratory pathogen H. influenzae degrades C3b (27). In parallel, Borrelia burgdorferi recruits plasminogen and inactivates C3b as well as C5 to escape the innate immune system (25). Similar to those findings, we observed that M. catarrhalis with plasmin at the bacterial surface also degrades C3b and C5, which most likely contributes to increased resistance against serum-mediated killing.…”

Section: Discussionsupporting

confidence: 78%

“…Another approach used by microbes to degrade the ECM is to attract the zymogen plasminogen. It has been reported that when plasminogen is bound to pathogens, it contributes to adherence to host tissues (29), degradation of ECM proteins resulting in increased invasion (30), and, finally, degradation of complement (25). Interestingly, our present results also suggest that M. catarrhalis utilizes host plasminogen to escape from the innate host defense.…”

Section: Discussionsupporting

confidence: 74%

“…C3b and C5 degradation by plasmin. Plasmin modulates the activity of the complement system by degrading complement factors C3b and C5 (21,25). We analyzed the degradation of C3b and C5 by plasminogen bound at the surface of M. catarrhalis or bound to UspA2/UspA2H by Western blotting.…”

Section: Methodsmentioning

confidence: 99%

“…C3 is an important component of the alternative complement pathway and is cleaved into C3b and further on into C3a after activation. Plasminogen interacts with C3b and inactivates it by cleavage (21,25). To analyze the degradation capacity of C3b when plasmin was bound to the surface of M. catarrhalis, plasminogen bound at the bacterial surface was activated with uPA, followed by the addition of pure C3b.…”

Section: Uspa2 and Uspa2h Are The Major Plasminogen-binding Proteins mentioning

confidence: 99%

See 3 more Smart Citations

Moraxella catarrhalis Binds Plasminogen To Evade Host Innate Immunity

et al. 2015

View full text Add to dashboard Cite

bSeveral bacterial species recruit the complement regulators C4b-binding protein, factor H, and vitronectin, resulting in resistance against the bactericidal activity of human serum. It was recently 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 Moraxella catarrhalis, which is commonly isolated from preschool children and adults with chronic obstructive pulmonary disease (COPD), significantly binds human plasminogen. Ubiquitous surface protein A2 (UspA2) and hybrid UspA2 (UspA2H) were identified as the plasminogen-binding factors in the outer membrane proteome of Moraxella. Furthermore, expression of a series of truncated recombinant UspA2 and UspA2H proteins 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 (K D ) values of full-length UspA2 30 -539 (amino acids 30 to 539 of UspA2) and full-length UspA2H 50 -720 for immobilized plasminogen were 4.8 ؋ 10 ؊8 M and 3.13 ؋ 10 ؊8 M, respectively, as measured by biolayer interferometry. Plasminogen bound to intact M. catarrhalis or to recombinant UspA2/UspA2H was readily accessible for a urokinase plasminogen activator that converted the zymogen into active plasmin, as verified by the specific substrate S-2251 and a degradation assay with fibrinogen. Importantly, plasmin bound at the bacterial surface also degraded C3b and C5, which consequently may contribute to 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.

show abstract

Section: Discussionsupporting

confidence: 78%

Section: Discussionsupporting

confidence: 74%

Section: Methodsmentioning

confidence: 99%

Section: Uspa2 and Uspa2h Are The Major Plasminogen-binding Proteins mentioning

confidence: 99%

See 2 more Smart Citations

Moraxella catarrhalis Binds Plasminogen To Evade Host Innate Immunity

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Plasminogen not only binds complement proteins such as C3 and C5, but has also been shown to cleave C3b and C5 upon activation to active plasmin (40). Interestingly, many pathogenic microorganisms acquire these inhibitors (including but not limited to C4BP and plasminogen) to establish an infection and evade the constant attack of complement (27,29,(41)(42)(43)(44).…”

Section: C4bp-plasminogen Interactionmentioning

confidence: 99%

A Novel Interaction between Complement Inhibitor C4b-binding Protein and Plasminogen That Enhances Plasminogen Activation

Agarwal¹,

Talens

Grandits

et al. 2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: There are multiple interactions between complement, coagulation, and fibrinolytic systems. Results: C4b-binding protein (C4BP) and plasminogen form a complex and C4BP augments plasminogen activation. Conclusion: C4BP affects the function of plasminogen. Significance: The interaction may regulate fibrinolysis and complement at the site of injury and/or during acute inflammation to maintain homeostasis.

show abstract

Strategies used by Leptospira spirochetes to evade the host complement system

Barbosa

Isaac

2020

FEBS Letters

View full text Add to dashboard Cite

Leptospires are highly invasive spirochetes equipped with efficient strategies for dissemination in the host. The Leptospira genus currently comprises 64 species divided into two major clades: the saprophytes composed of nonpathogenic, free-living organisms, and the pathogens encompassing all the species that cause mild or severe infections in humans and animals. While saprophytes are highly susceptible to the lytic action of the complement system, pathogenic (virulent) strains have evolved virulence strategies that allow efficient colonization of a variety of hosts and target organs, including mechanisms to circumvent hosts' innate and acquired immune responses. Pathogenic Leptospira avoid complement-mediated killing by recruiting host complement regulatory proteins and by targeting complement proteins using own and host-expressed proteases. This review outlines the role of complement in eradicating saprophytic Leptospira and the stratagems adopted by pathogenic Leptospira to maneuver the host complement system for their benefit.

show abstract

BBA70 of Borrelia burgdorferi Is a Novel Plasminogen-binding Protein

Cited by 59 publications

References 90 publications

Moraxella catarrhalis Binds Plasminogen To Evade Host Innate Immunity

Moraxella catarrhalis Binds Plasminogen To Evade Host Innate Immunity

A Novel Interaction between Complement Inhibitor C4b-binding Protein and Plasminogen That Enhances Plasminogen Activation

Strategies used by Leptospira spirochetes to evade the host complement system

Contact Info

Product

Resources

About