Inactivation of the antimicrobial peptide LL-37 by pathogenic Leptospira

Author(s)

Oliveira, Priscila N. ^{[1, 2]} ; Courrol, Daniella S. ^[1] ; Chura-Chambi, Rosa Maria ^[3] ; Morganti, Ligia ^[3] ; Souza, Gisele O. ^[2] ; Franzolin, Marcia R. ^[1] ; Wunder Jr, Elsio A. ; Heinemann, Marcos B. ^[2] ; Barbosa, Angela S. ^[1]

Affiliation

^[1] Inst Butantan, Lab Bacteriol, BR-05503900 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Dept Med Vet Prevent & Saude Anim, Fac Med Vet & Zootecnia, Sao Paulo - Brazil

^[3] Ctr Biotecnol, Inst Pesquisas Energet & Nucl IPEN CNEN SP, Sao Paulo - Brazil

• Document type: Journal article
• Source: Microbial Pathogenesis; v. 150, JAN 2021.
• Web of Science Citations: 0

Abstract

Leptospires are aerobic, Gram-negative spirochetes with a high invasive capacity. Pathogenic leptospires secrete proteases that inactivate a variety of host's proteins including molecules of the extracellular matrix and of the human complement system. This strategy, used by several pathogens of medical importance, contributes to bacterial invasion and immune evasion. In the current work we present evidence that Leptospira proteases also target human cathelicidin (LL-37), an antimicrobial peptide that plays an important role in the innate immune response. By using six Leptospira strains, four pathogenic and two saprophytic, we demonstrated that proteases present in the supernatants of pathogenic strains were capable of degrading LL-37 in a time-dependent manner, whereas proteolytic degradation was not observed with the supernatants of the two saprophytic strains. Inactivation of LL-37 was prevented by using the 1,10-phenanthroline inhibitor, thus suggesting the involvement of metalloproteinases in this process. In addition, the antibacterial activity of LL-37 against two Leptospira strains was evaluated. Compared to the saprophytic strain, a greater resistance of the pathogenic strain to the action of the peptide was observed. Our data suggest that the capacity to inactivate the host defense peptide LL-37 may be part of the virulence arsenal of pathogenic Leptospira, and we hypothesize that its inactivation by the bacteria may influence the outcome of the disease. (AU)

• FAPESP's process: 18/12896-2 - ROLE OF PROTEASES SECRETED BY LEPTOSPIRA IN THE DEGRADATION AND INACTIVATION OF HOST MOLECULES
• Grantee: Angela Silva Barbosa
• Support Opportunities: Regular Research Grants