Synergistic bactericidal effects of pairs of photosensitizer molecules activated by ultraviolet A light against bacteria in plasma

Abstract

Background The current approach to reducing bacterial contamination in blood transfusion products is through detection or pathogen reduction methods, some of which utilize ultraviolet (UV) light photosensitizers. A small number of photosensitizers are being used as single agents in combination with UV light, but their efficacy can be limited against some pathogens. Benzophenone (BP) and vitamins B1, B6, and K3 have been identified as effective UVA photosensitizers for inactivation of bacteria. We evaluated whether combining pairs of photosensitizers in this group would have synergistic bactericidal effects on Gram‐negative and Gram‐positive bacteria. Study Design and Methods Bacteria species of Escherichia coli, Bacillus cereus, Staphylococcus aureus, and Klebsiella pneumoniae were mixed with 0 to 100 mM concentrations of photosensitizers and exposed to UVA irradiation at 18 J/cm2 to assess their bactericidal effects. Results Single photosensitizers irradiated with UVA produced a range of bactericidal activity. When combined in pairs, all demonstrated some synergistic bactericidal effects with up to 4‐log reduction above the sum of activities of individual molecules in the pair against bacteria in plasma. Photosensitizer pairs with BP had the highest synergism across all bacteria. With vitamin K3 in the pair, synergism was evident for Gram‐positive but not for Gram‐negative bacteria. Vitamin B1 and vitamin B6 had the least synergism. These results indicate that a combination approach with multiple photosensitizers may extend effectiveness of pathogen reduction in plasma. Conclusions Combining photosensitizers in pathogen reduction methods could improve bactericidal efficacy and lead to use of lower concentrations of photosensitizers to reduce toxicities and unwanted side effects.

Viral reduction of human blood by ultraviolet A‐photosensitized vitamin K5

“…The UVA photosensitizer application appears to be an attractive approach for whole blood since it has already proved to be successful in platelet and plasma pathogen reduction. We have previously shown that the UVA/VK5 combination, as well as combinations of other vitamins with UVA light, can produce a reduction of bacteria in suspension 6,8 5,7 Our current results show that VK5 and UVA photodynamic treatment can also reduce viral titers in human plasma thus expanding the pathogen reduction potential of this combination.…”

“…Riboflavin binds to nucleic acids (DNA or RNA) bases leading to pathogen inactivation mainly through the generation of free reactive radicals, which enhances the formation of oxidized nucleotides 3,4 . Other approaches with different photosensitizers, such as benzophenone and vitamins B1, B6, K3, and K5 combined individually with UVA irradiation have been shown to be effective for the inactivation of bacteria in plasma 5–8 …”

Efficacy of violet–blue light to inactive microbial growth

“…Different abatement rate among bacterial strains may be explained by the different biological dispositions and expressions of endogenous photosensitizers in different species 20 .…”

Effects of low-light stress on aquacultural water quality and disease resistance in Nile tilapia

“…Light is considered the single most important contributor to bacterial die-off in aquaculture water [17,18]. A bactericidal effect of light was achieved that caused a rapid decrease in the colony-forming ability of bacteria [19,20]. Solar UV light is highly bactericidal, causing direct photobiological DNA damage in bacteria [21].…”