Abstract
Background Clostridium difficile is the leading cause of antibiotic-associated diarrhoea and pseudo membranous colitis in the developed world. The aim of this study was to explore whether Photodynamic Antimicrobial Chemotherapy (PACT) could be used as a novel approach to treating C. difficile infections.MethodsPACT utilises the ability of light-activated photosensitisers (PS) to produce reactive oxygen species (ROS) such as free radical species and singlet oxygen, which are lethal to cells. We screened thirteen PS against C. difficile planktonic cells, biofilm and germinating spores in vitro, and cytotoxicity of effective compounds was tested on the colorectal adenocarcinoma cell-line HT-29.ResultsThree PS were able to kill 99.9% of bacteria in both aerobic and anaerobic conditions, both in the planktonic state and in a biofilm, after exposure to red laser light (0.2 J/cm2) without harming model colon cells. The applicability of PACT to eradicate C. difficile germinative spores indirectly was also shown, by first inducing germination with the bile salt taurocholate, followed by PACT.ConclusionThis innovative and simple approach offers the prospect of a new antimicrobial therapy using light to treat C. difficile infection of the colon.
Highlights
IntroductionPhotodynamic antimicrobial chemotherapy (PACT) involves the combination of a lightsensitive dye, known as a photosensitiser (PS), and locally applied visible light [6,7]
The emergence of microbial resistance to most of the known classes of antibiotics has led to an urgent need to identify new antimicrobial strategies [1,2,3,4,5].Photodynamic antimicrobial chemotherapy (PACT) involves the combination of a lightsensitive dye, known as a photosensitiser (PS), and locally applied visible light [6,7]
The applicability of Photodynamic Antimicrobial Chemotherapy (PACT) to eradicate C. difficile germinative spores indirectly was shown, by first inducing germination with the bile salt taurocholate, followed by PACT. This innovative and simple approach offers the prospect of a new antimicrobial therapy using light to treat C. difficile infection of the colon
Summary
Photodynamic antimicrobial chemotherapy (PACT) involves the combination of a lightsensitive dye, known as a photosensitiser (PS), and locally applied visible light [6,7]. The excitation energy can be transferred from the excited triplet of the PS to triplet dioxygen forming a ground state PS and excited singlet oxygen (Type II mechanism) (Fig 1A). Accumulation of such reactive species, both radical and singlet oxygen, leads to irreversible damage to the target cell. The aim of this study was to explore whether Photodynamic Antimicrobial Chemotherapy (PACT) could be used as a novel approach to treating C. difficile infections
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