title: Bioavailability of the anti-clostridial bacteriocin thuricin CD in gastrointestinal tract.
abstract: Thuricin CD is a two component narrow spectrum bacteriocin comprising two peptides with targeted activity against Clostridium difficile. This study examined the bioavailability of thuricin with a view to developing it as an effective antimicrobial against intestinal infection. One of the peptides, Trn-β, was found to be degraded by the gastric enzymes pepsin and α-chymotrypsin both in vitro and in vivo, whereas Trn-α was resistant to digestion by these enzymes and hence was detected in the intestinal porcine digesta following oral ingestion by pigs. In order to determine if spores of the producing organism Bacillus thuringiensis DPC 6431 could be used to deliver the bacteriocin to the gut, spores were fed to 30 mice (approx. 10(8)-2×10(8) per animal) and their germination, growth and production of thuricin in the gastrointestinal tract (GIT) of the animals was monitored. Almost 99 % of the spores delivered to the GIT were excreted in the first 24 h and neither Trn-α nor Trn-β was detected in the gut or faecal samples of the test mice, indicating that ingestion of B. thuringiensis spores may not be a suitable vehicle for the delivery of thuricin CD. When thuricin CD was delivered rectally to mice (n = 40) and C. difficile shedding monitored at 1, 6, 12 and 24 h post-treatment, there was a >95 % (>1.5 log units) reduction of C. difficile 027 in the colon contents of infected mice (n = 10) 1 h post-treatment compared with the control group (n = 10; P<0.001). Furthermore, 6 h post-treatment there was a further 1.5 log reduction in C. difficile numbers (n = 10) relative to the control group (n = 10; P<0.05). These results would suggest that rectal administration of thuricin may be a promising mode of delivery of thuricin CD to the colon.
authors.affiliation: Alimentary Pharmabiotic Centre, University College Cork, Ireland.|Food Biosciences Department, Teagasc Food Research Centre, Moorepark, Fermoy, Co. Cork, Ireland.
authors.forename: Mary C
authors.initials: MC
authors.lastname: Rea
authors.affiliation: Alimentary Pharmabiotic Centre, University College Cork, Ireland.|Food Biosciences Department, Teagasc Food Research Centre, Moorepark, Fermoy, Co. Cork, Ireland.
authors.forename: Debebe
authors.initials: D
authors.lastname: Alemayehu
authors.affiliation: Microbiology Department, University College Cork, Ireland.|Alimentary Pharmabiotic Centre, University College Cork, Ireland.
authors.forename: Pat G
authors.initials: PG
authors.lastname: Casey
authors.affiliation: Alimentary Pharmabiotic Centre, University College Cork, Ireland.|Food Biosciences Department, Teagasc Food Research Centre, Moorepark, Fermoy, Co. Cork, Ireland.
authors.forename: Paula M
authors.initials: PM
authors.lastname: O'Connor
authors.affiliation: Teagasc, Pig Development Department, Animal and Grassland Research and Innovation Centre, Moorepark, Fermoy, Co. Cork, Ireland.
authors.forename: Peadar G
authors.initials: PG
authors.lastname: Lawlor
authors.affiliation: Teagasc, Pig Development Department, Animal and Grassland Research and Innovation Centre, Moorepark, Fermoy, Co. Cork, Ireland.
authors.forename: Maria
authors.initials: M
authors.lastname: Walsh
authors.affiliation: Department of Medicine, University College Cork, Ireland.|Alimentary Pharmabiotic Centre, University College Cork, Ireland.
authors.forename: Fergus
authors.initials: F
authors.lastname: Shanahan
authors.affiliation: Alimentary Health, Airport Business Park, Cork, Ireland.
authors.forename: Barry
authors.initials: B
authors.lastname: Kiely
authors.affiliation: Alimentary Pharmabiotic Centre, University College Cork, Ireland.|Food Biosciences Department, Teagasc Food Research Centre, Moorepark, Fermoy, Co. Cork, Ireland.
authors.forename: R Paul
authors.initials: RP
authors.lastname: Ross
authors.affiliation: Microbiology Department, University College Cork, Ireland.|Alimentary Pharmabiotic Centre, University College Cork, Ireland.
authors.forename: Colin
authors.initials: C
authors.lastname: Hill
mesh_terms: D000284:Administration, Oral; D000285:Administration, Rectal; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000032:analysis* / Q000493:pharmacokinetics*; D001413:Bacillus thuringiensis / Q000254:growth & development / Q000378:metabolism; D057138:Bacterial Shedding; D001430:Bacteriocins / Q000008:administration & dosage / Q000032:analysis* / Q000493:pharmacokinetics*; D001682:Biological Availability; D016360:Clostridioides difficile / Q000187:drug effects / Q000302:isolation & purification; D005243:Feces / Q000737:chemistry / Q000382:microbiology; D041981:Gastrointestinal Tract / Q000737:chemistry* / Q000382:microbiology; D051379:Mice; D013552:Swine
chemical_list: D000900:Anti-Bacterial Agents; D001430:Bacteriocins; C059740:thuricin