Inactivation of the antimicrobial peptide LL-37 by pathogenic Leptospira

Area of Science:

• Microbiology
• Immunology
• Bacterial Pathogenesis

Background:

• Leptospires are Gram-negative spirochetes known for their invasiveness.
• Pathogenic Leptospira secrete proteases to degrade host proteins, aiding invasion and immune evasion.
• Human cathelicidin (LL-37) is a crucial antimicrobial peptide in the innate immune response.

Purpose of the Study:

• To investigate whether Leptospira proteases target and inactivate the human antimicrobial peptide LL-37.
• To compare the LL-37 degrading activity between pathogenic and saprophytic Leptospira strains.
• To assess the role of LL-37 inactivation in Leptospira pathogenesis.

Main Methods:

• Supernatants from six Leptospira strains (four pathogenic, two saprophytic) were incubated with LL-37.
• LL-37 degradation was assessed over time.
• The effect of a metalloproteinase inhibitor (1,10-phenanthroline) on LL-37 inactivation was evaluated.
• Antibacterial activity of LL-37 against pathogenic and saprophytic Leptospira was tested.

Main Results:

• Proteases in pathogenic Leptospira supernatants degraded LL-37 in a time-dependent manner.
• No significant degradation of LL-37 was observed with saprophytic Leptospira supernatants.
• LL-37 inactivation was inhibited by 1,10-phenanthroline, indicating metalloproteinase involvement.
• Pathogenic Leptospira exhibited greater resistance to LL-37's antibacterial activity compared to saprophytic strains.

Conclusions:

• Leptospira proteases can inactivate the host defense peptide LL-37.
• This inactivation mechanism is associated with pathogenic Leptospira strains.
• LL-37 inactivation is a potential virulence factor for pathogenic Leptospira, possibly influencing disease outcomes.