Investigating LTX-315 as a Therapeutic Peptide: Antimicrobial Activity on Clinical Bacterial Isolates

The global rise of multidrug-resistant (MDR) pathogens has created an urgent need for alternative antimicrobial agents. In this study, we evaluated the antibacterial activity of LTX-315, a synthetic cationic 9-mer peptide originally developed as an oncolytic agent, against six ATCC reference strains and six clinical isolates, including methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae, MDR Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Burkholderia cepacia. LTX-315 exhibited broad-spectrum antibacterial activity, with MICs of 8-32 μM against reference strains and as low as 4 μM against several MDR clinical isolates, whereas chloramphenicol and kanamycin were ineffective. Double-disk diffusion assays indicated synergistic interactions with aminoglycosides, chloramphenicol, and vancomycin, and checkerboard assays confirmed synergy-to-additivity interactions with gentamicin and vancomycin against S. aureus (FICI 0.38-0.75), yielding fourfold to 16-fold reductions in antibiotic dose. These findings demonstrate that LTX-315 retains potent activity against clinically relevant MDR pathogens and may serve as both a standalone antimicrobial peptide and a potential antibiotic adjuvant.