Cerecidins, Novel Lantibiotics from Bacillus cereus with Potent Antimicrobial Activity

Cerecidins, Novel Lantibiotics from Bacillus cereus with Potent Antimicrobial Activity
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Cerecidins,来自蜡状芽孢杆菌的新型羊毛硫抗生素,具有有效的抗菌活性

DOI:
10.1128/aem.03751-13
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发表时间:
2014-02
影响因子:
4.4
通讯作者:
Zhong, Jin
Zhong, Jin
中科院分区:
生物学2区
文献类型:
--
作者:
Teng, Kunling;Sun, Shutao;Sun, Zhizeng;Zhong, Jin

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摘要羊毛硫抗生素是由核糖体合成并经修饰的抗菌肽,广泛存在于革兰氏阳性菌中,包括芽孢杆菌属的许多种。本研究通过基因组挖掘和PCR筛选,在蜡状芽孢杆菌菌株As 1.1846中发现了一个新的编码羊毛硫抗生素cerecidins的基因簇。与传统的II类羊毛硫抗生素不同的是,它包括七个串联的前体cerA基因、一个修饰基因(cerM)、两个加工基因(cerT和cerP)、一个孤儿调节基因(cerR)和两个免疫基因(cerF和cerE)。此外,一个前所未有的群体感应组件,comQXPA,插入cerM和cerR之间。在该株B中未检测到Cerecidins的表达。cereus,这可能是由于抑制cerM的转录。我们组成型共表达cerA基因和cerM在大肠杆菌中,和纯化的precerecidins进行蛋白水解处理与内切蛋白酶GluC和一个截短的版本的推定丝氨酸蛋白酶CerP。因此,获得了cerecidin A1和A7的两种天然变体,其含有在lantibiotics中很少发现的两个末端不重叠的硫醚环。Cerecidin A1和A7都对广谱革兰氏阳性菌有活性。Cerecidin A7,特别是其突变体Dhb 13 A,对多重耐药金黄色葡萄球菌(MDRSA),万古霉素耐药粪肠球菌(VRE),甚至链霉菌显示出显着的疗效。
ABSTRACT Lantibiotics are ribosomally synthesized and posttranslationally modified antimicrobial peptides that are widely produced by Gram-positive bacteria, including many species of the Bacillus group. In the present study, one novel gene cluster coding lantibiotic cerecidins was unveiled in Bacillus cereus strain As 1.1846 through genomic mining and PCR screening. The designated cer locus is different from that of conventional class II lantibiotics in that it included seven tandem precursor cerA genes, one modification gene (cerM), two processing genes (cerT and cerP), one orphan regulator gene (cerR), and two immunity genes (cerF and cerE). In addition, one unprecedented quorum sensing component, comQXPA, was inserted between cerM and cerR. The expression of cerecidins was not detected in this strain of B. cereus, which might be due to repressed transcription of cerM. We constitutively coexpressed cerA genes and cerM in Escherichia coli, and purified precerecidins were proteolytically processed with the endoproteinase GluC and a truncated version of putative serine protease CerP. Thus, two natural variants of cerecidins A1 and A7 were obtained which contained two terminal nonoverlapping thioether rings rarely found in lantibiotics. Both cerecidins A1 and A7 were active against a broad spectrum of Gram-positive bacteria. Cerecidin A7, especially its mutant Dhb13A, showed remarkable efficacy against multidrug-resistant Staphylococcus aureus (MDRSA), vancomycin-resistant Enterococcus faecalis (VRE), and even Streptomyces.
DOI: 10.1021/cb900194x
发表时间: 2009-10-16
影响因子: 4
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DOI: 10.3390/md11061878
发表时间: 2013-06-03
期刊: Marine drugs
影响因子: 5.4
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发表时间: 2013-03
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DOI: 10.1021/bi300255s
发表时间: 2012-05-29
期刊: Biochemistry
影响因子: 2.9
作者:
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通讯作者: van der Donk WA
DOI: 10.1016/j.lwt.2007.11.011
发表时间: 2008-12
期刊: Lwt - Food Science and Technology
影响因子: --
作者:
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通讯作者: Xingrong Ju;Yu-long Gao;Minglan Yao;Y. Qian