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来自产2,3-丁二醇肺炎克雷伯菌的毒力因子的失活

Inactivation of the virulence factors from 2,3-butanediol-producing Klebsiella pneumoniae.

作者信息

Huynh Duyen Thi Ngoc, Kim Ah-Young, Seol In-Hye, Jung Samuel, Lim Min-Cheol, Lee Jeong-A, Jo Mi-Rae, Choi Soo-Jin, Kim Borim, Lee Jinwon, Kim Wooki, Kim Young-Rok

机构信息

Graduate School of Biotechnology, Kyung Hee University, Yongin, 446-701, Republic of Korea.

Department of Food Science and Biotechnology, Kyung Hee University, Yongin, 446-701, Republic of Korea.

出版信息

Appl Microbiol Biotechnol. 2015 Nov;99(22):9427-38. doi: 10.1007/s00253-015-6861-1. Epub 2015 Aug 4.

Abstract

The microbiological production of 2,3-butanediol (2,3-BDO) has attracted considerable attention as an alternative way to produce high-value chemicals from renewable sources. Among the number of 2,3-BDO-producing microorganisms, Klebsiella pneumoniae has been studied most extensively and is known to produce large quantity of 2,3-BDO from a range of substrates. On the other hand, the pathogenic characteristics of the bacteria have limited its industrial applications. In this study, two major virulence traits, outer core LPS and fimbriae, were removed through homologous recombination from 2,3-BDO-producing K. pneumoniae 2242 to expand its uses to the industrial scale. The K. pneumoniae 2242 ∆wabG mutant strain was found to have an impaired capsule, which significantly reduced its ability to bind to the mucous layer and evade the phagocytic activity of macrophage. The association with the human ileocecal epithelial cell, HCT-8, and the bladder epithelial cell, T-24, was also reduced dramatically in the K. pneumoniae 2242 ∆fimA mutant strain that was devoid of fimbriae. However, the growth rate and production yield for 2,3-BDO were unaffected. The K. pneumoniae strains developed in this study, which are devoid of the major virulence factors, have a high potential for the efficient and sustainable production of 2,3-BDO.

摘要

微生物生产2,3-丁二醇(2,3-BDO)作为从可再生资源生产高价值化学品的一种替代方法已引起了广泛关注。在众多能够生产2,3-丁二醇的微生物中,肺炎克雷伯菌得到了最为广泛的研究,并且已知该菌能够利用多种底物大量生产2,3-丁二醇。另一方面,该细菌的致病特性限制了其在工业上的应用。在本研究中,通过同源重组从产2,3-丁二醇的肺炎克雷伯菌2242中去除了两个主要的毒力性状,即外核心脂多糖和菌毛,以将其应用扩展到工业规模。发现肺炎克雷伯菌2242 ∆wabG突变株的荚膜受损,这显著降低了其与黏液层结合以及逃避巨噬细胞吞噬活性的能力。在不含菌毛的肺炎克雷伯菌2242 ∆fimA突变株中,其与人回盲肠上皮细胞HCT-8和膀胱上皮细胞T-24的黏附也显著降低。然而,其2,3-丁二醇的生长速率和产量未受影响。本研究中构建的不含主要毒力因子的肺炎克雷伯菌菌株在高效、可持续生产2,3-丁二醇方面具有很高的潜力。

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