Combinatorial antimicrobial potential of secondary metabolites and bacteriophages against multi-drug-resistant...

Uropathogenic Escherichia coli (UPEC), the leading cause of urinary tract infections, has developed resistance to multiple antibiotics, creating an urgent need for alternative therapeutics.

A bacterial isolate exhibiting antimicrobial activity against multidrug-resistant (MDR) UPEC was screened. Its secondary metabolites were extracted and analyzed using high-performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS), and gas chromatography-mass spectrometry (GC-MS). Antimicrobial activity was evaluated for the purified secondary metabolite (SM) extract alone and in combination with bacteriophages.

HPLC revealed a major bioactive peak corresponding to polymyxin B sulfate, confirmed by LC-MS with a dominant peak at 1185 Da. GC-MS identified additional minor pyrrolizidine derivatives with potential antibacterial activity. The polymyxin-like SM (PSM) extract showed potent antimicrobial effects against UPEC and other uropathogens. Notably, co-treatment with bacteriophages significantly reduced the minimum inhibitory concentration (MIC), indicating a synergistic effect.

Bacterial secondary metabolites, particularly polymyxin-like extracts, exhibit strong antimicrobial activity against MDR UPEC. Their synergistic interaction with bacteriophages highlights a promising combined antimicrobial approach to combat MDR uropathogens.