Department of Physical and Life Sciences, Nevada State College, Henderson, Nevada, USA.
School of Life Sciences, University of Nevada, Las Vegas, Las Vegas, Nevada, USA.
Antimicrob Agents Chemother. 2018 Sep 24;62(10). doi: 10.1128/AAC.02251-17. Print 2018 Oct.
infection (CDI) is the leading cause of antibiotic-associated diarrhea and has gained worldwide notoriety due to emerging hypervirulent strains and the high incidence of recurrence. We previously reported protection of mice from CDI using the antigerminant bile salt analog CamSA. Here we describe the effects of CamSA in the hamster model of CDI. CamSA treatment of hamsters showed no toxicity and did not affect the richness or diversity of gut microbiota; however, minor changes in community composition were observed. Treatment of challenged hamsters with CamSA doubled the mean time to death, compared to control hamsters. However, CamSA alone was insufficient to prevent CDI in hamsters. CamSA in conjunction with suboptimal concentrations of vancomycin led to complete protection from CDI in 70% of animals. Protected animals remained disease-free at least 30 days postchallenge and showed no signs of colonic tissue damage. In a delayed-treatment model of hamster CDI, CamSA was unable to prevent infection signs and death. These data support a putative model in which CamSA reduces the number of germinating spores but does not keep all of the spores from germinating. Vancomycin halts division of any vegetative cells that are able to grow from spores that escape CamSA.
感染（CDI）是抗生素相关性腹泻的主要原因，由于新兴的高毒力菌株和高复发率，它在全球范围内引起了关注。我们之前报道了使用抗萌发胆汁盐类似物 CamSA 保护小鼠免受 CDI 的侵害。在这里，我们描述了 CamSA 在仓鼠 CDI 模型中的作用。CamSA 处理仓鼠没有显示出毒性，也不会影响肠道微生物群落的丰富度或多样性；然而，观察到群落组成有轻微变化。与对照仓鼠相比，用 CamSA 处理受挑战的仓鼠将平均死亡时间延长了一倍。然而，CamSA 单独使用不足以预防仓鼠 CDI。CamSA 与低浓度万古霉素联合使用可使 70%的动物完全免受 CDI 的侵害。受保护的动物在挑战后至少 30 天内保持无病状态，并且没有结肠组织损伤的迹象。在仓鼠 CDI 的延迟治疗模型中，CamSA 无法预防感染迹象和死亡。这些数据支持了一个假设模型，即 CamSA 减少了发芽孢子的数量，但不能阻止所有孢子发芽。万古霉素阻止任何能够从逃避 CamSA 的孢子生长的营养细胞分裂。
