Synergistic Antibacterial and Antibiofilm Effects of (KW) 4 in Combination With Antibiotics Against Listeria monocytogenes

ABSTRACT The efficacy of antibiotics is increasingly limited by microbial resistance, necessitating the development of alternative therapeutic strategies. The combination of conventional antibiotics with antimicrobial peptides (AMPs) has emerged as a promising approach for enhancing antibacterial activity. Listeria monocytogenes is an important foodborne pathogen that causes listeriosis—a severe invasive infection associated with high morbidity and mortality, particularly in pregnant women, neonates, older adults, and immunocompromised individuals. (KW) 4 is a peptide composed of four repeats of lysine (Lys) and tryptophan (Trp), exhibiting both cationic and hydrophobic characteristics. Because of these structural properties, (KW) 4 reportedly exhibits antimicrobial activities. However, its combined effects with conventional antibiotics have not yet been investigated. Here, we evaluated the synergistic effects of (KW) 4 in combination with cefotaxime or tetracycline against L. monocytogenes . These combinations displayed synergistic antimicrobial activity, as determined by the fractional inhibitory concentration index, and were more effective at lower concentrations than the individual agents. The combination exerted sustained bactericidal effects for up to 12 h and inhibited biofilm formation. No significant hemolytic activity or cytotoxicity was observed in RAW264.7 cells under the tested conditions. These results suggested that (KW) 4 has potential as an antibiotic adjuvant against L. monocytogenes .