胆汁有抗菌作用：非共轭和共轭胆盐对金黄色葡萄球菌的体外抗菌活性

In Vitro Antibacterial Activity of Unconjugated and Conjugated Bile Salts on Staphylococcus aureus

 

Thippeswamy H. Sannasiddappa1 *†，Peter A. Lund2和Simon R. Clarke1 * 1英国雷丁大学生物科学学院 2英国伯明翰伯明翰大学生物科学学院微生物与感染研究所

胆汁盐是有效的抗微生物剂，是肠内先天防御的重要组成部分，可以保护免受侵入性生物的侵害。它们在确定肠道的微生物生态学中起重要作用，其水平的改变可导致病原体的定植增加。

我们之前已经证明了人类结肠模型中机会性病原体金黄色葡萄球菌的存活。因此，研究金黄色葡萄球菌和胆汁盐之间的相互作用是理解其在宿主肠中定殖的能力的重要因素。利用胆汁盐也可以为开发控制耐药细菌的治疗策略提供新的途径。

尽管如此，胆汁盐对金黄色葡萄球菌的抗菌活性仍然知之甚少。在这项研究中，我们研究了主要的非结合和共轭胆汁盐对金黄色葡萄球菌的抗菌作用。发现了几种浓度依赖性抗菌机制。最低抑制浓度的未缀合胆汁盐（分别为20和1mM的胆酸和脱氧胆酸）杀死金黄色葡萄球菌，这与膜破裂增加和细胞内容物泄漏有关。未结合的胆汁盐（分别为8和0.4mM的胆酸和脱氧胆酸）和亚抑制浓度的共轭胆盐（甘氨酸和30％的牛磺胆酸）仍然能够通过破坏质子动力和增加的膜渗透性来抑制生长。我们还证明，未结合的胆汁盐对金黄色葡萄球菌具有比结合的胆汁盐更强的抗菌作用。

　

In Vitro Antibacterial Activity of Unconjugated and Conjugated Bile Salts on Staphylococcus aureus

Thippeswamy H. Sannasiddappa1*†, Peter A. Lund2 and Simon R. Clarke1*
1School of Biological Sciences, University of Reading, Reading, United Kingdom
2Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Birmingham, United Kingdom

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 Staphylococcus aureus in the human colonic model. Thus investigating the interaction between S. aureus 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 S. aureus is poorly understood. In this study, we investigated the antibacterial effects of the major unconjugated and conjugated bile salts on S. aureus. 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 S. aureus, 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 S. aureus than conjugated bile salts.

Frontiers | In Vitro Antibacterial Activity of Unconjugated and Conjugated Bile Salts on Staphylococcus aureus | Microbiology https://www.frontiersin.org/articles/10.3389/fmicb.2017.01581/full