Assessment of the potential for resistance to antimicrobial violet-blue light in Staphylococcus aureus

Abstract

BackgroundAntimicrobial violet-blue light in the region of 405 nm is emerging as an alternative technology for hospital decontamination and clinical treatment. The mechanism of action is the excitation of endogenous porphyrins within exposed microorganisms, resulting in ROS generation, oxidative damage and cell death. Although resistance to 405 nm light is not thought likely, little evidence has been published to support this. This study was designed to establish if there is potential for tolerance development, using the nosocomial pathogen Staphylococcus aureus as the model organism.MethodsThe first stage of this study investigated the potential for S. aureus to develop tolerance to high-intensity 405 nm light if pre-cultured in low-level stress violet-blue light (≤1 mW/cm2) conditions. Secondly, the potential for tolerance development in bacteria subjected to repeated sub-lethal exposure was compared by carrying out 15 cycles of exposure to high-intensity 405 nm light, using a sub-lethal dose of 108 J/cm2. Inactivation kinetics and antibiotic susceptibility were also compared.ResultsWhen cultured in low-level violet-blue light conditions, S. aureus required a greater dose of high-intensity 405 nm light for complete inactivation, however this did not increase with multiple (3) low-stress cultivations. Repeated sub-lethal exposures indicated no evidence of bacterial tolerance to 405 nm light. After 15 sub-lethal exposures 1.2 and 1.4 log10 reductions were achieved for MSSA and MRSA respectively, which were not significantly different to the initial 1.3 log10 reductions achieved (P = 0.242 & 0.116, respectively). Antibiotic susceptibility was unaffected, with the maximum change in zone of inhibition being ± 2 mm.ConclusionsRepeated sub-lethal exposure of non-proliferating S. aureus populations did not affect the susceptibility of the organism to 405 nm light, nor to antibiotics. Culture in low-level violet-blue light prior to 405 nm light exposure may increase oxidative stress responses in S. aureus, however, inactivation still occurs and results demonstrate that this is unlikely to be a selective process. These results demonstrate that tolerance from repeated exposure is unlikely to occur, and further supports the potential development of 405 nm light for clinical decontamination and treatment applications.

Light as a Broad-Spectrum Antimicrobial

“…The available data ( Maclean et al, 2008a , 2009 ; Endarko et al, 2012 ) suggest a sigmoidal dose–response curve implying that, as similarly observed with low-level oxidative stress ( Kumar and Imlay, 2013 ), a sub-lethal light dose may be indefinitely tolerated by organisms with appropriate detoxifying systems. The existence of adaptive tolerance is supported by the finding that growth in low levels of blue light protects somewhat against subsequent high-intensity challenge ( Tomb et al, 2017 ). With repeated sub-lethal dosage, resistance to blue light has been reported ( Guffey et al, 2013 ) although this point remains contentious ( de Sousa N.T.…”

“…With repeated sub-lethal dosage, resistance to blue light has been reported ( Guffey et al, 2013 ) although this point remains contentious ( de Sousa N.T. et al, 2015 ; Tomb et al, 2017 ). The importance of appropriate dosing and considerations of light transmission through tissue are clearly of particular importance given that blue light can promote biofilm formation ( Tschowri et al, 2009 ; Mussi et al, 2010 ).…”

Evaluating the Potential for Resistance Development to Antimicrobial Blue Light (at 405 nm) in Gram-Negative Bacteria: In vitro and in vivo Studies

“…Antimicrobial blue light (aBL; at 405 nm) is a novel strategy that has demonstrated efficacy against a variety of microbial pathogens both in vitro and in vivo , regardless of their AMR status ( Dai et al, 2012 ; Zhang et al, 2014 ; Hessling et al, 2017 ; Tomb et al, 2017 ; Wang et al, 2017 ). However, due to the limited studies that have investigated the potential for resistance development to aBL by microbial pathogens, it is difficult to predict whether future aBL-resistance development will become a concern.…”

“…However, due to the limited studies that have investigated the potential for resistance development to aBL by microbial pathogens, it is difficult to predict whether future aBL-resistance development will become a concern. Presently, the studies that have evaluated the potential for resistance development to aBL have suggested it is unlikely to occur through serial exposure ( Zhang et al, 2014 ; Amin et al, 2016 ; Tomb et al, 2017 ). The only investigation that has suggested the potential for resistance development to aBL was a study carried out by Guffey et al (2013) , which found that Staphylococcus aureus developed resistance following 7 cycles of aBL exposure ( Guffey et al, 2013 ).…”

Photo-inactivation ofNeisseria gonorrhoeae: A paradigm changing approach for combating antibiotic-resistant gonococcal infection

“…The advantages of aBL over traditional antibiotics include rapid action and equal inactivation effectiveness independent of antibiotic resistance (21,22). It is also currently thought that bacteria are less able to develop resistance to aBL than to traditional antibiotics because of the multi-target characteristic of aBL (21,22,25). In comparison to traditional antimicrobial photodynamic therapy, aBL is appealing in that it inactivates bacteria (renders bacteria unable to multiply) without the involvement of exogenous photosensitizers (26)(27)(28)(29)(30)(31)(32).…”