Application of LpxC enzyme inhibitor to inhibit some fast-growing bacteria in human gut bacterial culturomics
Application of LpxC enzyme inhibitor to inhibit some fast-growing bacteria in human gut bacterial culturomics
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DOI：
10.1186/s12866-019-1681-6
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发表时间：
2019-12-30
期刊：
影响因子：
4.2
通讯作者：
Bi, Yujing
中科院分区：
文献类型：
--
作者：
Hou, Fengyi;Chang, Yuxiao;Bi, Yujing
背景资料：培养组学可以确定使用不同策略培养的微生物的痕迹，并通过基质辅助激光解吸/电离飞行时间质谱或16 S rDNA测序进行鉴定。然而，为了满足微生物的所有需求并分离尽可能多的物种，必须使用多种培养条件，这带来了繁重的工作量。此外，快速生长的细菌（例如，大肠杆菌）通过占据空间和消耗营养物质而超过培养中生长缓慢的细菌。此外，一些细菌（例如，假单胞菌）通过分泌抗菌代谢物来抑制其他细菌，使得难以分离具有较低能力的细菌。结果：我们将对大多数革兰氏阴性菌具有抗菌活性的LpxC酶抑制剂CHIR-090应用于人新鲜粪便的培养组学。CHIR-090的抗菌活性首先在五种革兰氏阴性细菌（大肠杆菌、铜绿假单胞菌、肺炎克雷伯菌、普通变形杆菌和普通拟杆菌）上进行评估，所有这些细菌通常都从人肠道中分离。然后，我们评估了合适的抑制剂浓度。最后，将CHIR-090应用于血培养瓶进行细菌培养。共鉴定了5个样品中的102种。其中，我们发现了一个新的物种，两个以前没有报道过的物种在人类肠道，和11个以前没有从人类分离的物种。coli、铜绿假单胞菌、克雷伯氏菌（K. pneumoniae，Pro.寻常型，但不是B型。普通人与非抑制剂组相比，CHIR-090使细菌分离增加了23.50%，其中包括4种在人类中未报道的菌种和1种新菌种。在培养组学中应用LpxC酶抑制剂增加了从人肠道分离的物种数量。
Background: Culturomics can ascertain traces of microorganisms to be cultivated using different strategies and identified by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry or 16S rDNA sequencing. However, to cater to all requirements of microorganisms and isolate as many species as possible, multiple culture conditions must be used, imposing a heavy workload. In addition, the fast-growing bacteria (e.g., Escherichia) surpass the slow-growing bacteria in culture by occupying space and using up nutrients. Besides, some bacteria (e.g., Pseudomonas) suppress others by secreting antibacterial metabolites, making it difficult to isolate bacteria with lower competence. Applying inhibitors to restrain fast-growing bacteria is one method to cultivate more bacterial species from human feces.Results: We applied CHIR-090, an LpxC enzyme inhibitor that has antibacterial activity against most Gram-negative bacteria, to culturomics of human fresh feces. The antibacterial activity of CHIR-090 was first assessed on five Gram-negative species of bacteria (Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus vulgaris, and Bacteroides vulgatus), all of which are commonly isolated from the human gut. Then, we assessed suitable concentrations of the inhibitor. Finally, CHIR-090 was applied in blood culture bottles for bacterial cultivation. In total, 102 species from five samples were identified. Of these, we found one new species, two species not reported previously in the human gut, and 11 species not previously isolated from humans.Conclusions: CHIR-090 can suppress E. coli, P. aeruginosa, K. pneumoniae, Pro. vulgaris, but not B. vulgatus. Compared with the non-inhibitor group, CHIR-090 increased bacteria isolation by 23.50%, including four species not reported in humans and one new species. Application of LpxC enzyme inhibitor in culturomics increased the number of species isolated from the human gut.