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Identification and functional characterization of a conserved sea snake cathelicidin SS-CATH against multidrug-resistant Gram-negative bacteria

Year: 2026
Type: article
Abstract: Sea snakes are fully marine-adapted reptiles living under unique environmental pressures, including high salinity and exposure to potentially pathogenic Gram-negative bacteria. Cathelicidin antimicrobial peptides (AMPs) are important components of vertebrate innate immunity, and their mature peptide sequences are typically highly diverse among species. Here, genome mining and comparative sequence analysis across multiple sea snake species were performed and an unusually conserved mature cathelicidin peptide, designated SS-CATH, was identified from the sea snake species of Hydrophis cyanocinctus, Hydrophis major, Hydrophis elegans, and Hydrophis ornatus. Functional characterization demonstrated that SS-CATH possesses potent and broad-spectrum bactericidal activity against multidrug-resistant (MDR) Gram-negative pathogens. Moreover, SS-CATH effectively inhibits biofilm formation, eradicates pre-established biofilms, and eliminates rifampicin-induced persisters. Mechanistic studies demonstrated that SS-CATH disrupted bacterial membranes and induced oxidative stress. SS-CATH also exhibited DNA-binding activity in vitro. In a murine peritonitis model, SS-CATH significantly improved host survival and reduced bacterial loads across multiple organs. The sequence conservation of SS-CATH suggests possible functional constraint, while its antibacterial activities highlight its potential role in host defense. These findings suggest SS-CATH as a promising therapeutic candidate against MDR Gram-negative infections and provide novel insights into innate immune adaptation in marine reptiles.
Language: English
Subfield: Microbiology
Open Access status: diamond
OpenAlex ID: W7225628389
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