Photodamage to multidrug-resistant gram-positive and gram-negative bacteria by 870 nm/930 nm light potentiates erythromycin, tetracycline and ciprofloxacin.
We have previously shown that 870 nm/930 nm wavelengths cause photodamage at physiologic temperatures in methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli via generation of endogenous radical oxygen species (ROS) and decreased plasma membrane potentials (Delta Psi p). We tested MRSA (Strain HSJ216) in vitro with sublethal 870 nm/930 nm laser energy and subinhibitory concentrations of erythromycin, tetracycline, penicillin, rifampin and trimethoprim to surmise whether photodamage could potentiate these antimicrobials. We also tested patient isolates of fluoroquinolone-resistant MRSA and E. coli with subinhibitory concentrations of ciprofloxacin. In MRSA (Strain HSJ216) we observed 97% potentiation (a 1.5 log(10) CFU decrease) with erythromycin and tetracycline. In patient isolates of E. coli, we observed 100% potentiation (>3 log(10) CFU decrease) in all irradiated samples with ciprofloxacin. To assess whether staphyloxanthin pigment conferred protection against the generated ROS, we created an isogenic carotenoid-deficient mutant of S. aureus that was significantly less tolerant of 870 nm/930 nm exposure than the wild type strain (P < 0.0001). We suggest that antibiotic potentiation results from a photobiological attenuation of ATP-dependent macromolecular synthetic pathways, similar to that observed with daptomycin, via disruption of Delta Psi p and endogenous generation of ROS. With erythromycin, tetracycline and ciprofloxacin, attenuation of energy-dependent efflux systems is also a possibility.
Bornstein
Eric
E
Nomir Medical Technologies, Waltham, MA, USA. ebornstein@nomirmedical.com
Gridley
Scott
S
Wengender
Paul
P
Robbins
Alan
A
D000890:Anti-Infective Agents / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology; D004917:Erythromycin / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects / Q000528:radiation effects; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000528:radiation effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000528:radiation effects*; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000528:radiation effects; D013752:Tetracycline / Q000494:pharmacology
D000890:Anti-Infective Agents; D002939:Ciprofloxacin; D004917:Erythromycin; D013752:Tetracycline