Mechanisms and determinants of bacterial susceptibility to antimicrobial Blue Light: From chromophores to transcriptomes

Antimicrobial blue light (aBL) is emerging as a promising non-pharmacological antimicrobial strategy with multitarget activity and a low risk of resistance development. Its effects are primarily mediated by endogenous porphyrins, but additional chromophores such as flavins and bacterial pigments can also contribute. In this review, we summarize current evidence on these photosensitizers and discuss how their diversity underlies species-dependent susceptibility, with special emphasis on the variable responses of Streptococcus and Enterococcus spp. At the molecular level, aBL-induced reactive oxygen species (ROS) damage DNA, proteins, and membranes, disrupting metabolic pathways, efflux pumps, and membrane integrity. Genetic determinants, including porphyrin biosynthesis genes, cell envelope regulators, and components of the SOS and oxidative stress responses, further influence susceptibility. Transcriptomic studies reveal global shifts affecting stress responses, energy metabolism, motility, membrane remodeling, metal ion regulation, and virulence-associated functions. Additional microbial determinants, such as biofilm formation, virulence factors, and antibiotic resistance profiles, modulate treatment outcomes, while environmental and physiological parameters (growth phase, inoculum density, temperature, wavelength, and irradiance) strongly impact efficacy. Altogether, these findings indicate that aBL efficacy is shaped by a complex interplay of chromophore availability, genetic background, physiological state, and external conditions. Clarifying these mechanisms is essential to optimize aBL for clinical and industrial applications. In summary, this review provides a comprehensive overview of the molecular and physiological bases of bacterial susceptibility to aBL and outlines key gaps that must be addressed to translate this modality into routine antimicrobial practice. • Endogenous chromophore diversity explains species-specific aBL susceptibility. • aBL generates multitarget oxidative damage with with no confirmed stable resistance reported to date. • Key determinants include envelope structure, stress regulons, and DNA repair pathways. • Transcriptomics reveals broad metabolic and regulatory responses to aBL. • Mechanistic insights may guide clinical optimization of aBL protocols.