Beyond Resistance: Tolerance and Resilience of Bacteria to Photodynamic and Oxidative Stress

The increasing reliance on light-based antimicrobial technologies, such as antimicrobial blue light (aBL) and antimicrobial photodynamic inactivation (aPDI), underscores the urgent need to comprehend bacterial survival strategies beyond conventional resistance. Two key phenotypes-tolerance and resilience-have emerged as critical but often conflated mechanisms by which bacteria withstand oxidative and photodynamic stress. While tolerance refers to delayed bacterial killing without changes in MIC, resilience encompasses the active restoration of cellular function after transient stress exposure. Both phenomena may impair treatment outcomes and contribute to long-term persistence, even in the absence of genetic resistance. This review dissects the molecular mechanisms underlying tolerance and resilience, with a focus on their relevance to bacterial responses to reactive oxygen species generated by light-based or chemical stressors. The regulatory and effector overlap between these phenotypes is examined, including antioxidant defense systems, DNA repair pathways, and metabolic rewiring. Furthermore, the role of phenotypic heterogeneity and cross-stress protection in blurring the boundary between survival and recovery is discussed, highlighting challenges in experimental interpretation. Finally, the implications of these adaptive strategies are evaluated in the context of antimicrobial efficacy and safety, with an emphasis on kinetic assays and multidimensional profiling as tools to capture complex treatment outcomes. Clarifying the distinction between tolerance and resilience may help guide the development of robust and evolutionarily stable antimicrobial phototherapies.