title: Development of Photodynamic Antimicrobial Chemotherapy (PACT) for Clostridium difficile.
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.
  
  
  CONCLUSIONS
  This innovative and simple approach offers the prospect of a new antimicrobial therapy using light to treat C. difficile infection of the colon.
authors: Microbial Diseases, UCL Eastman Dental Institute, London, United Kingdom; Research Department of Tissue & Energy, UCL, London, United Kingdom.
authors: Luisa
authors: L
authors: De Sordi
authors: Research Department of Tissue & Energy, UCL, London, United Kingdom; Division of Gastrointestinal Services, University College Hospital, London, United Kingdom.
authors: M Adil
authors: MA
authors: Butt
authors: Research Department of Tissue & Energy, UCL, London, United Kingdom.
authors: Hayley
authors: H
authors: Pye
authors: Research Department of Tissue & Energy, UCL, London, United Kingdom; Division of Gastrointestinal Services, University College Hospital, London, United Kingdom.
authors: Darina
authors: D
authors: Kohoutova
authors: Research Department of Tissue & Energy, UCL, London, United Kingdom.
authors: Charles A
authors: CA
authors: Mosse
authors: Department of Chemistry, Imperial College London, London, United Kingdom; PhotoBiotics Ltd, Chemistry Building, Imperial College London, London, United Kingdom.
authors: Gokhan
authors: G
authors: Yahioglu
authors: Department of Chemistry, Imperial College London, London, United Kingdom.
authors: Ioanna
authors: I
authors: Stamati
authors: PhotoBiotics Ltd, Chemistry Building, Imperial College London, London, United Kingdom; Department of Life Sciences, Imperial College London, London, United Kingdom.
authors: Mahendra
authors: M
authors: Deonarain
authors: Organix Ltd, Colchester, United Kingdom; School of Biological Sciences, University of Essex, Colchester, United Kingdom.
authors: Sinan
authors: S
authors: Battah
authors: Public Health Laboratory London, Pathology & Pharmacy Building, London, United Kingdom.
authors: Derren
authors: D
authors: Ready
authors: Microbial Diseases, UCL Eastman Dental Institute, London, United Kingdom.
authors: Elaine
authors: E
authors: Allan
authors: Microbial Diseases, UCL Eastman Dental Institute, London, United Kingdom.
authors: Peter
authors: P
authors: Mullany
authors: Research Department of Tissue & Energy, UCL, London, United Kingdom; Division of Gastrointestinal Services, University College Hospital, London, United Kingdom.
authors: Laurence B
authors: LB
authors: Lovat
mesh_terms: D018441:Biofilms / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002735:Chlorophyllides; D016360:Clostridioides difficile / Q000187:drug effects* / Q000528:radiation effects; D019073:HT29 Cells; D006801:Humans; D008751:Methylene Blue / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011166:Porphyrins / Q000494:pharmacology
chemical_list: D002735:Chlorophyllides; D017319:Photosensitizing Agents; D011166:Porphyrins; C062985:phytochlorin; C053434:Talaporfin; D008751:Methylene Blue