An Insight on Bacterial Cellular Targets of Photodynamic Inactivation

Abstract

The emergence of microbial resistance is becoming a global problem in clinical and environmental areas. As such, the development of drugs with novel modes of action will be vital to meet the threats created by the rise in microbial resistance. Microbial photodynamic inactivation is receiving considerable attention for its potentialities as a new antimicrobial treatment. This review addresses the interactions between photosensitizers and bacterial cells (binding site and cellular localization), the ultrastructural, morphological and functional changes observed at initial stages and during the course of photodynamic inactivation, the oxidative alterations in specific molecular targets, and a possible development of resistance.

Photodynamic Action against Wastewater Microorganisms and Chemical Pollutants: An Effective Approach with Low Environmental Impact

“…Although the occurrence of each type of interaction between PS and the surroundings highly depends on the chemical structure of the PS and according to the literature, porphyrin derivatives PS tend to generate ROS via the energy transference to O 2 , the higher PDI efficiency in the tests using WW as medium suspension shown in our study could be explained by the high presence of organic matter in the medium. It is well known that ROS have an extremely short lifetime due to their very unstable electronic configuration and their diffusion range is consequently small and dependent on the environment type [21]. The fact that the WW used as WW medium have a high quantity of organic matter could allow for the appearance of different microenvironments with different 1 O 2 diffusion rates and lifetimes [38,39]; additionally, the presence of compounds able to generate ROS [41] can affect the rate of bacterial inactivation and consequently be responsible for the differences observed in the inactivation rate between the tests performed in PBS and WW medium.…”

Photodynamic Inactivation of Bacteria: Finding the Effective Targets

“…In Gram-negative bacteria, beside the thin peptidoglycan layer, the presence of an intricate outer membrane creates an impermeable barrier to antimicrobial agents [16]. The outer membrane consists of glycolipids in the outer leaflet, mainly lipopolysaccharides, lipoproteins and β-barrel proteins, lipoteichoic acids, a phospholipid bilayer in the inner leaflet, which anchors these constituents and the peptidoglycan (2-7 nm) [3]. In Gram-positive bacteria the wall is formed by only one thick peptidoglycan layer, surface proteins (fibronectin, fibrinogen, elastin) are attached to peptidoglycan, to teichoic acids (adhesins) or to stem peptides within the peptidoglycan layers.…”

“…While antibiotics act on a specific cellular constituent, such as a key fitting into a lock, PDI, due to the reactive oxygen species formed during the lighting process, acts upon various critical molecular targets such as proteins, lipids and/or nucleic acids [3,4]. In spite of the multi-target nature of PDI it is generally accepted that the main targets in bacteria are the external structures, cytoplasmic membrane and cell walls [2,[5][6][7].…”

Antibacterial photodynamic therapy: overview of a promising approach to fight antibiotic-resistant bacterial infections

“…The extracellular and intracellular targets of the commonly used PSs are summarized in Table 3 and a generic overview of possible target loci is provided in Figure 3. For a more detailed overview of the targets, readers are referred to a recent review [100]. Since APDT efficacy largely depends on the localization of the PS, the following subsections focus of the physical and biochemical hurdles that impair the PSs in reaching the target sites.…”

“…So although nucleic acids may be oxidized as a result of APDT, the redox modifications can be reverted and the cells may not undergo cell death as a direct result of nucleic acid damage. Moreover, DNA damage was only found when a remarkable amount of bacterial cells had been photo-inactivated, pleading against this mechanism as a primary cause of cell death [100]. More focused studies are needed to elucidate the role of nucleic acid oxidation in the context of cytotoxicity.…”