CXCL12a, an antimicrobial chemokine, contains a C-terminal helical structural fragment that exerts potent antimicrobial activity in largemouth bass (Micropterus salmoides).

Abstract

CXCL12 is a broad-spectrum antimicrobial protein across diverse species and plays a pivotal role in innate immunity. However, the specific structure underlying this activity remain poorly characterized. In this study, we reported that largemouth bass (Micropterus salmoides) encodes an evolutionarily conserved CXCL12a, which kills bacteria in a dose-dependent manner. MsCXCL12a directly kill bacteria through bacterial cell membrane disruption, cytoplasmic leakage and subsequent cell death. Notably, MsCXCL12a also exhibits calcium-independent bacterial aggregation property. By performing structure-charge analysis on the basis of its secondary structure, we identified that the C-terminal peptide of MsCXCL12a (MsCXCL12a) retains broad-spectrum, stable antimicrobial activity while exhibiting negligible cytotoxicity. MsCXCL12aalso kills bacteria by disrupting bacterial cell membrane integrity. Although MsCXCL12aretains the aggregation-mediating capability of MsCXCL12a, its aggregation efficiency is significantly reduced compared to MsCXCL12a. Using a largemouth bass model challenged with a lethal dose of Aeromonas hydrophila, MsCXCL12a and MsCXCL12acan substantially reduce tissue bacterial loads and mortality rates. These findings underscored the functional convergence between chemokine and antimicrobial peptide. The antimicrobial efficacy of MsCXCL12ain the fish model suggested its potential as a novel therapeutic candidate for bacterial infections, warranting further investigation into its translational applications.