Abstract
Leptospires are highly motile spirochetes equipped with strategies for efficient invasion and dissemination within the host. Our group previously demonstrated that pathogenic leptospires secrete proteases capable of cleaving and inactivating key molecules of the complement system, allowing these bacteria to circumvent host's innate immune defense mechanisms. Given the successful dissemination of leptospires during infection, we wondered if such proteases would target a broader range of host molecules. In the present study, the proteolytic activity of secreted leptospiral proteases against a panel of extracellular matrix (ECM) and plasma proteins was assessed. The culture supernatant of the virulent L. interrogans serovar Kennewicki strain Fromm (LPF) degraded human fibrinogen, plasma fibronectin, gelatin, and the proteoglycans decorin, biglycan, and lumican. Interestingly, human plasminogen was not cleaved by proteases present in the supernatants. Proteolytic activity was inhibited by 1,10-phenanthroline, suggesting the participation of metalloproteases. Moreover, production of proteases might be an important virulence determinant since culture-attenuated or saprophytic Leptospira did not display proteolytic activity against ECM or plasma components. Exoproteomic analysis allowed the identification of three metalloproteases that could be involved in the degradation of host components. The ability to cleave conjunctive tissue molecules and coagulation cascade proteins may certainly contribute to invasion and tissue destruction observed upon infection with Leptospira.
Highlights
Leptospira are long, thin, spiral-shaped, and highly motile Gramnegative bacteria
We reported the secretion of proteases by pathogenic Leptospira as a novel complement evasion mechanism displayed by these spirochetes (Fraga et al, 2014)
We evaluated the proteolytic activity of leptospiral secreted proteases against extracellular matrix (ECM) and plasma proteins
Summary
Leptospira are long, thin, spiral-shaped, and highly motile Gramnegative bacteria. These spirochetes can be either non-pathogenic free-living organisms or pathogenic, having the potential to cause disease in animals and humans. Pathogenic leptospires efficiently spread and propagate in susceptible hosts. They are equipped with strategies to modulate the surrounding microenvironment in the host, including mechanisms to circumvent host’s immune responses (Meri et al, 2005; Barbosa et al, 2009). By hydrolyzing diverse proteinaceous substrates of the host, bacterial proteases play a crucial role in colonization and spreading, allowing evasion of innate immune responses and contributing to disruption of tissue integrity
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.