Strategies to potentiate antimicrobial photoinactivation by overcoming resistant phenotypes

Abstract

Conventional antimicrobial strategies have become increasinglyineffective due to the emergence of multidrug resistance amongpathogenic microorganisms. The need to overcome these deficiencieshas triggered the exploration of alternative treatmentsand unconventional approaches towards controlling microbialinfections. Photodynamic therapy (PDT) was originally establishedas an anticancer modality and is currently used in thetreatment of age-related macular degeneration. The concept ofphotodynamic inactivation requires cell exposure to light energy,typically wavelengths in the visible region that causes theexcitation of photosensitizer molecules either exogenous orendogenous, which results in the production of reactive oxygenspecies (ROS). ROS produce cell inactivation and death throughmodification of intracellular components. The versatile characteristicsof PDT prompted its investigation as an anti-infectivediscovery platform. Advances in understanding of microbialphysiology have shed light on a series of pathways, andphenotypes that serve as putative targets for antimicrobial drugdiscovery. Investigations of these phenotypic elements in concertwith PDT have been reported focused on multidrug effluxsystems, biofilms, virulence and pathogenesis determinants.In many instances the results are promising but only preliminaryand require further investigation. This review discusses thedifferent antimicrobial PDT strategies and highlights the needfor highly informative and comprehensive discovery approaches.