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未结合和结合胆汁盐对……的抗菌活性

Antibacterial Activity of Unconjugated and Conjugated Bile Salts on .

作者信息

Sannasiddappa Thippeswamy H, Lund Peter A, Clarke Simon R

机构信息

School of Biological Sciences, University of ReadingReading, United Kingdom.

Institute of Microbiology and Infection, School of Biosciences, University of BirminghamBirmingham, United Kingdom.

出版信息

Front Microbiol. 2017 Aug 23;8:1581. doi: 10.3389/fmicb.2017.01581. eCollection 2017.

Abstract

Bile salts are potent antimicrobial agents and are an important component of innate defenses in the intestine, giving protection against invasive organisms. They play an important role in determining microbial ecology of the intestine and alterations in their levels can lead to increased colonization by pathogens. We have previously demonstrated survival of the opportunistic pathogen in the human colonic model. Thus investigating the interaction between and bile salts is an important factor in understanding its ability to colonize in the host intestine. Harnessing bile salts may also give a new avenue to explore in the development of therapeutic strategies to control drug resistant bacteria. Despite this importance, the antibacterial activity of bile salts on is poorly understood. In this study, we investigated the antibacterial effects of the major unconjugated and conjugated bile salts on . Several concentration-dependent antibacterial mechanisms were found. Unconjugated bile salts at their minimum inhibitory concentration (cholic and deoxycholic acid at 20 and 1 mM, respectively) killed , and this was associated with increased membrane disruption and leakage of cellular contents. Unconjugated bile salts (cholic and deoxycholic acid at 8 and 0.4 mM, respectively) and conjugated bile salts (glycocholic and taurocholic acid at 20 mM) at their sub inhibitory concentrations were still able to inhibit growth through disruption of the proton motive force and increased membrane permeability. We also demonstrated that unconjugated bile salts possess more potent antibacterial action on than conjugated bile salts.

摘要

胆汁盐是强效抗菌剂,是肠道固有防御的重要组成部分,可抵御入侵微生物。它们在决定肠道微生物生态方面发挥着重要作用,其水平的改变会导致病原体的定植增加。我们之前已经在人类结肠模型中证明了机会性病原体的存活。因此,研究[病原体名称未给出]与胆汁盐之间的相互作用是理解其在宿主肠道定植能力的一个重要因素。利用胆汁盐也可能为探索控制耐药菌的治疗策略开辟一条新途径。尽管胆汁盐很重要,但其对[病原体名称未给出]的抗菌活性却知之甚少。在本研究中,我们研究了主要的未结合型和结合型胆汁盐对[病原体名称未给出]的抗菌作用。发现了几种浓度依赖性抗菌机制。未结合型胆汁盐在其最低抑菌浓度(胆酸和脱氧胆酸分别为20和1 mM)时可杀死[病原体名称未给出],这与膜破坏增加和细胞内容物泄漏有关。未结合型胆汁盐(胆酸和脱氧胆酸分别为8和0.4 mM)和结合型胆汁盐(甘氨胆酸和牛磺胆酸为20 mM)在其亚抑菌浓度下仍能够通过破坏质子动力和增加膜通透性来抑制生长。我们还证明,未结合型胆汁盐对[病原体名称未给出]的抗菌作用比结合型胆汁盐更强。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8909/5572772/761b419736b5/fmicb-08-01581-g001.jpg

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