Emergence of an unconventional Enterobacter cloacae-derived Iturin A C-15 as a potential therapeutic agent against methicillin-resistant Staphylococcus aureus

Antimicrobial resistance poses a significant global health threat by reducing the effectiveness of conventional antibiotics, particularly against pathogens like Methicillin-resistant Staphylococcus aureus (MRSA). This study investigates the antimicrobial potential of rhizospheric soil bacteria from Prosopis cineraria (Sangri) in the Thar Desert. Bacterial strains isolated from these samples were observed to produce secondary metabolites, notably, Iturin A C-15 cyclic lipopeptide (SS1-3-P) which was extracted from strain Enterobacter cloacae SS1-3 and was purified and characterized using reverse-phase HPLC, ESI-LC/MS, Nile-Red Assay, and FT-IR analysis. The presence of the Iturin A biosynthetic gene cluster was confirmed using gene-specific polymerase chain reaction and the biocompatibility of the purified product was assessed on HEK-293, WI38, and human RBCs. The potential of SS1-3-P to bind to and destroy MRSA membranes was validated using molecular dynamics simulation along with membranolysis and membrane depolarization assays. Antimicrobial assays like growth curve analysis, field emission scanning electron microscopy, and ROS generation confirmed the efficacy of SS1-3-P against clinical MRSA. Furthermore, the antibiofilm and anti-virulence properties of SS1-3-P were studied meticulously. Studies on NIH/3T3 cell lines and a murine excisional wound model showed significant wound-healing attributes of the lipopeptide. These results highlight the potential of desert ecosystems in developing effective antimicrobial therapies against recalcitrant nosocomial pathogens like MRSA.