Abstract
Due to rapidly growing antimicrobial resistance, there is an urgent need to develop alternative, non-antibiotic strategies. Recently, numerous light-based approaches, demonstrating killing efficacy regardless of microbial drug resistance, have gained wide attention and are considered some of the most promising antimicrobial modalities. These light-based therapies include five treatments for which high bactericidal activity was demonstrated using numerous in vitro and in vivo studies: antimicrobial blue light (aBL), antimicrobial photodynamic inactivation (aPDI), pulsed light (PL), cold atmospheric plasma (CAP), and ultraviolet (UV) light. Based on their multitarget activity leading to deleterious effects to numerous cell structures—i.e., cell envelopes, proteins, lipids, and genetic material—light-based treatments are considered to have a low risk for the development of tolerance and/or resistance. Nevertheless, the most recent studies indicate that repetitive sublethal phototreatment may provoke tolerance development, but there is no standard methodology for the proper evaluation of this phenomenon. The statement concerning the lack of development of resistance to these modalities seem to be justified; however, the most significant motivation for this review paper was to critically discuss existing dogma concerning the lack of tolerance development, indicating that its assessment is more complex and requires better terminology and methodology.
Highlights
Increasing antimicrobial resistance due to overuse and misuse of antibiotics is a significant concern and extremely dangerous health threat facing modern medicine [1]
After conducting a critical review, we describe here recently published studies concerning the risk of developing tolerance and resistance to phototreatments, i.e., antimicrobial photodynamic inactivation, antimicrobial blue light, and other alternative light-based approaches, such as UV irradiation and pulsed light
The use of rose Bengal (RB) photoactivated with green light resulted in the development of tolerance, with lower susceptibility to RB–antimicrobial photodynamic inactivation (aPDI) starting from the fifth consecutive cycle, expressed as a reduction in aPDI antimicrobial efficacy by approximately 3 log10 units
Summary
Increasing antimicrobial resistance due to overuse and misuse of antibiotics is a significant concern and extremely dangerous health threat facing modern medicine [1]. The most recent study concerning the tolerance to aPDI was performed by Snell et al (2021) who revealed that repeated exposure to MB-mediated aPDI lead to increased sur-vival rate of two reference S. aureus strains, i.e., HG003 and ATCC 25923, after 7day-lasting consecutive treatment. These results are contradictory to these published by Pedigo et al (2009) even though using the same S. aureus strains. The observed variations in methodological approaches are the reason why, in our previously published study [31], we proposed the following protocol to determine the risk of developing tolerance/resistance in response to sublethal light-based treatments (Figure 3):. - Phenotypic stability testing should be performed [37,41]
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