Evolution of the primate cathelicidin. Correlation between structural variations and antimicrobial activity

Area of Science:

• Evolutionary biology
• Immunology
• Biochemistry

Background:

• Cathelicidins are crucial host defense peptides involved in innate immunity.
• The human cathelicidin antimicrobial peptide (CAMP) gene codes for LL-37, a key effector molecule.
• Understanding primate cathelicidin evolution provides insights into host-pathogen interactions.

Purpose of the Study:

• To analyze the evolution and functional variation of cathelicidin genes across 20 primate species.
• To investigate the structural and functional differences of derived antimicrobial peptides.
• To elucidate the impact of evolutionary changes on antimicrobial activity and host cell interactions.

Main Methods:

• Sequencing and phylogenetic analysis of cathelicidin genes in diverse primate species.
• Chemical synthesis and characterization of selected primate cathelicidin peptides.
• In vitro antimicrobial activity assays under varying salt and medium conditions.
• Assessment of peptide structure and interaction with host cells.

Main Results:

• Cathelicidin genes show strong positive selection, favoring charge alterations over hydrophobicity.
• Two distinct peptide types emerged: salt-independent (macaque, leaf-eating monkey) and salt-dependent (human, orangutan, hylobates, callithrix).
• Peptide behavior in solution (structured vs. unstructured) correlates with antimicrobial activity and host cell interactions.

Conclusions:

• Primate cathelicidin evolution has generated peptides with divergent antimicrobial mechanisms.
• Structural and functional variations influence both direct antimicrobial potency and accessory immune functions.
• These findings highlight the dynamic evolution of innate immune effectors in primates.