Alimentary Pharmabiotic Centre, University College Cork, Ireland.
Food Biosciences Department, Teagasc Food Research Centre, Moorepark, Fermoy, Co. Cork, Ireland.
Microbiology (Reading). 2014 Feb;160(Pt 2):439-445. doi: 10.1099/mic.0.068767-0. Epub 2013 Nov 28.
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.
梭菌丁素 CD 是一种由两种靶向针对艰难梭菌的肽组成的两组件窄谱细菌素。本研究考察了梭菌丁素的生物利用度，以期将其开发为一种针对肠道感染的有效抗菌剂。研究发现，其中一种肽 Trn-β 在体外和体内均被胃蛋白酶和 α-糜蛋白酶降解，而 Trn-α 则不受这些酶的消化，因此在猪口服摄入后可在猪肠道内容物中检测到。为了确定产菌苏云金芽孢杆菌 DPC 6431 的孢子是否可用于将细菌素递送至肠道，将孢子喂给 30 只小鼠（每只动物约 10(8)-2×10(8)个孢子），监测孢子在动物胃肠道（GIT）中的发芽、生长和梭菌丁素的产生情况。约 99%的递送至 GIT 的孢子在 24 小时内被排出，且在试验小鼠的肠道或粪便样本中均未检测到 Trn-α 或 Trn-β，表明摄入苏云金芽孢杆菌孢子可能不是递送梭菌丁素 CD 的合适载体。当将梭菌丁素 CD 通过直肠递送至小鼠（n=40）并在治疗后 1、6、12 和 24 小时监测艰难梭菌脱落时，与对照组（n=10；P<0.001）相比，在感染小鼠的结肠内容物中，治疗后 1 小时艰难梭菌 027 的减少量超过 95%（>1.5 对数单位）（n=10）。此外，与对照组（n=10；P<0.05）相比，治疗后 6 小时艰难梭菌数量进一步减少了 1.5 对数单位。这些结果表明，直肠给予梭菌丁素可能是将梭菌丁素 CD 递送至结肠的一种有前途的给药方式。
