Emergence of an unconventional Enterobacter cloacae-derived Iturin A C-15 as a potential therapeutic agent against...

Area of Science:

• Microbiology
• Biochemistry
• Pharmacology

Background:

• Antimicrobial resistance is a critical global health challenge, diminishing antibiotic efficacy against pathogens like Methicillin-resistant Staphylococcus aureus (MRSA).
• Exploring novel antimicrobial sources, such as extremophilic microorganisms from desert environments, is crucial for discovering new therapeutic agents.

Purpose of the Study:

• To investigate the antimicrobial potential of rhizospheric bacteria from Prosopis cineraria in the Thar Desert.
• To isolate, characterize, and evaluate the efficacy of a novel lipopeptide, SS1-3-P, against MRSA and assess its wound-healing properties.

Main Methods:

• Isolation and characterization of bacterial strains and secondary metabolites, including Iturin A C-15 cyclic lipopeptide (SS1-3-P) using HPLC, ESI-LC/MS, Nile-Red Assay, and FT-IR.
• Confirmation of the Iturin A biosynthetic gene cluster via PCR; assessment of biocompatibility on cell lines (HEK-293, WI38) and human red blood cells (RBCs).
• Validation of MRSA membrane interaction using molecular dynamics simulations, membranolysis, and depolarization assays; antimicrobial efficacy confirmed by growth curve analysis, SEM, and ROS generation; antibiofilm, anti-virulence, and wound healing studies.

Main Results:

• Strain Enterobacter cloacae SS1-3 produced Iturin A C-15 cyclic lipopeptide (SS1-3-P).
• SS1-3-P demonstrated significant binding to and destruction of MRSA membranes, confirmed by in vitro assays and molecular dynamics simulations.
• The lipopeptide exhibited potent antimicrobial activity against clinical MRSA strains, alongside antibiofilm, anti-virulence, and notable wound-healing capabilities in a murine model.

Conclusions:

• Rhizospheric bacteria from the Thar Desert harbor potent antimicrobial compounds like SS1-3-P.
• SS1-3-P is a promising candidate for developing novel therapeutic strategies against multidrug-resistant pathogens, including MRSA.
• The study underscores the therapeutic potential of desert microbial resources for combating infectious diseases and promoting tissue regeneration.