Degradation of human antimicrobial peptide LL-37 by Staphylococcus aureus-derived proteinases

Area of Science:

• Microbiology
• Immunology
• Biochemistry

Background:

• Cathelicidin LL-37 is a human antimicrobial peptide with potent activity against Staphylococcus aureus.
• Staphylococcus aureus produces proteinases that may degrade LL-37, potentially contributing to immune evasion.

Purpose of the Study:

• To investigate the susceptibility of LL-37 to degradation by Staphylococcus aureus metalloproteinase (aureolysin) and V8 protease.
• To determine the impact of proteolytic degradation on LL-37's antibacterial activity and identify active fragments.

Main Methods:

• Incubation of LL-37 with purified aureolysin and V8 protease.
• Time- and concentration-dependent degradation assays.
• Mass spectrometry analysis of LL-37 fragments.
• Antibacterial activity assays against Staphylococcus aureus strains with varying aureolysin production.

Main Results:

• Aureolysin rapidly cleaved and inactivated LL-37 at multiple sites (Arg19-Ile20, Arg23-Ile24, Leu31-Val32).
• V8 protease efficiently cleaved LL-37 at Glu16-Phe17, producing an active C-terminal fragment (LL-17-37).
• LL-17-37 retained significant antibacterial activity against S. aureus, comparable to full-length LL-37.
• S. aureus strains producing aureolysin showed reduced susceptibility to LL-17-37.

Conclusions:

• Aureolysin production by S. aureus contributes to resistance against the human antimicrobial peptide LL-37.
• The C-terminal region of LL-37 (LL-17-37) is crucial for its antibacterial activity.
• Bacterial proteinase activity represents a mechanism for S. aureus to evade the host innate immune system.