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Development of Photodynamic Antimicrobial Chemotherapy (PACT) for Clostridium difficile.

De Sordi L, Butt MA, Pye H, Kohoutova D, Mosse CA, Yahioglu G, Stamati I, Deonarain M, Battah S, Ready D, Allan E, Mullany P, Lovat LB - PLoS ONE (2015)

Bottom Line: Clostridium difficile is the leading cause of antibiotic-associated diarrhoea and pseudo membranous colitis in the developed world.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.This innovative and simple approach offers the prospect of a new antimicrobial therapy using light to treat C. difficile infection of the colon.

View Article: PubMed Central - PubMed

Affiliation: Microbial Diseases, UCL Eastman Dental Institute, London, United Kingdom; Research Department of Tissue & Energy, UCL, London, United Kingdom.

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.

Methods: 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.

Results: 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.

Conclusion: This innovative and simple approach offers the prospect of a new antimicrobial therapy using light to treat C. difficile infection of the colon.

No MeSH data available.


Related in: MedlinePlus

Mechanism of PACT (A) and post PACT live/dead viability assay on C. difficile with light only (B), and PB031 (C) staining alive (green) and dead (red) bacteria.Scale bars represent 10 μM.
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pone.0135039.g001: Mechanism of PACT (A) and post PACT live/dead viability assay on C. difficile with light only (B), and PB031 (C) staining alive (green) and dead (red) bacteria.Scale bars represent 10 μM.

Mentions: Photodynamic antimicrobial chemotherapy (PACT) involves the combination of a light-sensitive dye, known as a photosensitiser (PS), and locally applied visible light [6,7]. Upon illumination of the PS at one or more wavelengths corresponding to the absorption peaks, the excited molecule can react with a target (molecular oxygen or other targets within biological systems) by electron transfer generating radical species (Type I mechanism). Alternatively, 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.


Development of Photodynamic Antimicrobial Chemotherapy (PACT) for Clostridium difficile.

De Sordi L, Butt MA, Pye H, Kohoutova D, Mosse CA, Yahioglu G, Stamati I, Deonarain M, Battah S, Ready D, Allan E, Mullany P, Lovat LB - PLoS ONE (2015)

Mechanism of PACT (A) and post PACT live/dead viability assay on C. difficile with light only (B), and PB031 (C) staining alive (green) and dead (red) bacteria.Scale bars represent 10 μM.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4551672&req=5

pone.0135039.g001: Mechanism of PACT (A) and post PACT live/dead viability assay on C. difficile with light only (B), and PB031 (C) staining alive (green) and dead (red) bacteria.Scale bars represent 10 μM.
Mentions: Photodynamic antimicrobial chemotherapy (PACT) involves the combination of a light-sensitive dye, known as a photosensitiser (PS), and locally applied visible light [6,7]. Upon illumination of the PS at one or more wavelengths corresponding to the absorption peaks, the excited molecule can react with a target (molecular oxygen or other targets within biological systems) by electron transfer generating radical species (Type I mechanism). Alternatively, 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.

Bottom Line: Clostridium difficile is the leading cause of antibiotic-associated diarrhoea and pseudo membranous colitis in the developed world.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.This innovative and simple approach offers the prospect of a new antimicrobial therapy using light to treat C. difficile infection of the colon.

View Article: PubMed Central - PubMed

Affiliation: Microbial Diseases, UCL Eastman Dental Institute, London, United Kingdom; Research Department of Tissue & Energy, UCL, London, United Kingdom.

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.

Methods: 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.

Results: 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.

Conclusion: This innovative and simple approach offers the prospect of a new antimicrobial therapy using light to treat C. difficile infection of the colon.

No MeSH data available.


Related in: MedlinePlus