Tetracyclines function as dual-action light-activated antibiotics

Abstract

Antimicrobial photodynamic inactivation (aPDI) employs photosensitizing dyes activated by visible light to produce reactive oxygen species. aPDI is independent of the antibiotic resistance status of the target cells, and is thought unlikely to produce resistance itself. Among many PS that have been investigated, tetracyclines occupy a unique niche. They are potentially dual-action compounds that can both kill bacteria under illumination, and prevent bacterial regrowth by inhibiting ribosomes. Tetracycline antibiotics are regarded as bacteriostatic rather than bactericidal. Doxycycline (DOTC) is excited best by UVA light (365 nm) while demeclocycline (DMCT) can be efficiently activated by blue light (415 nm) as well as UVA. Both compounds were able to eradicate Gram-positive (methicillin-resistant Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria (>6 log(10) steps of killing) at concentrations (10–50μM) and fluences (10-20J/cm2). In contrast to methylene blue, MB plus red light, tetracyclines photoinactivated bacteria in rich growth medium. When ~3 logs of bacteria were killed with DMCT/DOTC+light and the surviving cells were added to growth medium, further bacterial killing was observed, while the same experiment with MB allowed complete regrowth. MIC studies were carried out either in the dark or exposed to 0.5mW/cm2 blue light. Up to three extra steps (8-fold) increased antibiotic activity was found with light compared to dark, with MRSA and tetracycline-resistant strains of E. coli. Tetracyclines can accumulate in bacterial ribosomes, where they could be photoactivated with blue/UVA light producing microbial killing via ROS generation.

Effects of 462 nm Light-Emitting Diode on the Inactivation of Escherichia coli and a Multidrug-Resistant by Tetracycline Photoreaction

“…The aPDI treatment has become a potential alternative or adjuvant in treating SSRIs [ 23 , 24 ], and it is used to decrease nosocomial infections of the skin with multiresistant bacteria [ 25 ]. The application of aPDI to E. coli with tetracyclines, such as demeclocycline [ 26 , 27 ], doxycycline [ 26 , 27 ], chlortetracycline [ 28 ], oxytetracycline [ 27 ], and tetracycline [ 26 , 29 ], requires a UV light for the inactivation of E. coli . Demeclocycline is a semisynthetic tetracycline.…”

“…Demeclocycline is a semisynthetic tetracycline. It has been reported that demeclocycline can be excited by violet light (415 nm) and UVA light (365 nm), and it is able to eradicate Gram-positive (MRSA) and Gram-negative ( E. coli ) bacteria [ 26 ]. Lights with shorter wavelengths and high energy may cause damage to cells.…”

Using Colistin as a Trojan Horse: Inactivation of Gram-Negative Bacteria with Chlorophyllin

“…The possible observed additive effect of colistin and illumination on the proliferation of E. coli (and to a lower extent on S. Typhimurium) could not only be explained by delayed cell growth due to illumination as reported before [60]. To date, light-activation was only reported for tetracyclines [76] and the antitumor antibiotics ravidomycin and desacetylravidomycin [77], but this finding deserves further investigation of polymyxins.…”

Radical-scavenging and Pro-/anti-inflammatory Activity of Tetracycline and Related Phenolic Compounds With or Without Visible Light Irradiation

“…These degradation products resulting from VLI may possibly affect inflammatory mediators. On the other hand, Ya et al have reported that tetracyclines (TC, DC, MC) can accumulate in bacterial ribosomes, where they are photoactivated by blue light (BL) (415 nm) and ultraviolet light (UVA) (365 nm), resulting in microbial killing via ROS generation, and that no photobleaching of tetracyclines was observed upon exposure to either UVA or BL at <50 J/cm 2 (34). Our present results indicated that MC, QU and RE were fairly photostable in RAW264.7 cells.…”