Development of Photodynamic Antimicrobial Chemotherapy (PACT) for Clostridium difficile

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. PACT...

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Published in:PloS one 2015-08, Vol.10 (8), p.e0135039
Main Authors: De Sordi, Luisa, Butt, M Adil, Pye, Hayley, Kohoutova, Darina, Mosse, Charles A, Yahioglu, Gokhan, Stamati, Ioanna, Deonarain, Mahendra, Battah, Sinan, Ready, Derren, Allan, Elaine, Mullany, Peter, Lovat, Laurence B
Format: Article
Language:English
Subjects:
Adenocarcinoma
Anaerobic conditions
Anti-infective agents
Antibiotics
Antiinfectives and antibacterials
Bacillus
Bacteria
Bile
Biofilms
Biofilms - drug effects
Cell Survival - drug effects
Cell Survival - radiation effects
Chemistry
Chemotherapy
Chlorophyllides
Chromatography
Clostridioides difficile - drug effects
Clostridioides difficile - radiation effects
Clostridium difficile
Clostridium infections
Colitis
Colon
Complications and side effects
Cytotoxicity
Diarrhea
Dosage and administration
Drug resistance
Drug therapy
Energy
Free radicals
Germination
HT29 Cells
Humans
Infections
Laboratories
Light
Mass spectrometry
Methylene Blue - pharmacology
Microbial Sensitivity Tests
NMR
Nuclear magnetic resonance
Oxygen
Photochemotherapy
Photodynamic therapy
Photosensitizing Agents - pharmacology
Physiological aspects
Planktonic cells
Porphyrins - pharmacology
Prognosis
Reactive oxygen species
Scientific imaging
Singlet oxygen
Spores
Toxicity
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Summary: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. PACT 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. Three 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. This innovative and simple approach offers the prospect of a new antimicrobial therapy using light to treat C. difficile infection of the colon.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0135039