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-b, was found to be degraded by the gastric enzymes pepsin and a-chymotrypsin both in vitro and in vivo, whereas Trn-a 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 -2¾10 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-a nor Trn-b 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 (n540) and C. difficile shedding monitored at 1, 6, 12 and 24 h post-treatment, there was a .95 % (

Gleaning Insights from Fecal Microbiota Transplantation and Probiotic Studies for the Rational Design of Combination Microbial Therapies

“…Both lacticin 3147, produced by Lactococcus lactis strain DP3147 (141,142), and thuricin CD, produced by Bacillus thuringiensis DPC 6431 (143), are bacteriocins that are inhibitory to C. difficile. Thuricin CD has potent activity against C. difficile without any apparent significant effects on other gut commensals (91,143); however, mouse studies suggest that B. thuringiensis DPC 6431 spores pass through the mouse GI tract without germinating, limiting the probiotic potential of this strain (144). In contrast, lacticin 3147 is inhibitory toward other gut commensals (141), likely limiting its potential for restoring colonization resistance.…”

Analysis of Bacterial Communities during Clostridium difficile Infection in the Mouse

“…Recent experiments suggest roles in resisting CDI for a number of bacterial species in the GI tract (4,5). Resistance to C. difficile colonization can involve the inactivation of germinants (the molecules that cause the spore, the infectious form of C. difficile, to return to the vegetative state and produce toxins) (6) and production of inhibitory small molecules (7). Members of healthy human GI tract microbiota may also stimulate host immune responses that prevent C. difficile establishment (8).…”

Antimicrobial antagonists against food pathogens: a bacteriocin perspective

“…These screening programmes are being aided by the use of genome mining and mass spectrometry to find and characterise new bacteriocins while new engineering based approaches are being used in parallel to improve previously identified bacteriocins for particular applications /targets. There is great potential to carry out investigations that would assess the impact of bacteriocins on an entire food microbial consortia as has been done previously to assess the impact of bacteriocins on gut microbial populations [56,59].…”