Low-dose blue light extends the antibacterial spectrum of bacitracin against Escherichia coli

Bacitracin, a narrow-spectrum antimicrobial peptide, is primarily effective against Gram-positive bacteria but lacks efficacy against Gram-negative bacteria like Escherichia coli due to intrinsic resistance. The global rise in antibiotic resistance necessitates innovative strategies to enhance the utility of existing drugs. Blue light (BL) has emerged as a promising non-pharmacological antimicrobial approach. This study investigates whether low-dose BL can broaden bacitracin's antibacterial spectrum to include E. coli, potentially reducing reliance on combination therapies.

One laboratory strain (DH5α) and three clinical isolates of bacitracin-resistant E. coli were examined. Bacitracin's antibacterial efficacy was assessed using the broth microdilution method to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration. Cultures were treated with varying bacitracin concentrations, with or without sub-therapeutic BL exposure (405 ± 5 nm, 120 J/cm²). Potentiation effects were evaluated through MIC/minimum bactericidal concentration determinations and time-course viability assays at multiple time points.

BL alone had minimal impact on E. coli growth. However, combining BL with bacitracin significantly sensitized all strains, reducing bacitracin's MIC by ≥8-fold to ≥512-fold, depending on the strain. For two strains, MICs dropped from 256-512 to <1 µg/mL, representing a >256-fold reduction. Time-course viability assays confirmed a potent bactericidal effect within 2 h post-exposure.

A non-pharmacological intervention with low-dose BL reverses E. coli's resistance to bacitracin, likely through photodamage affecting cell permeability or resistance genes, requiring further investigation. This synergy enhances bacitracin's potential, offering a cost-effective and translatable approach to combat antibiotic resistance.