Contributions of the σ(W) , σ(M) and σ(X) regulons to the lantibiotic resistome of Bacillus subtilis.

Contributions of the σ(W) , σ(M) and σ(X) regulons to the lantibiotic resistome of Bacillus subtilis.
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DOI:
10.1111/mmi.12380
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发表时间:
2013-11
影响因子:
3.6
通讯作者:
Helmann JD
Helmann JD
中科院分区:
生物学2区
文献类型:
--
作者:
Kingston AW;Liao X;Helmann JD

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在枯草芽孢杆菌中,细胞质外功能(ECF)σ因子σM、σW和σX都有助于对硫醚抗生素的抗性。乳链菌肽是一种典型的羊毛硫抗生素,具有双重作用模式:它通过结合脂质II抑制细胞壁合成,并且这种复合物还在细胞质膜上形成孔。这些活动可以在结合脂质II的乳链菌肽铰链区变体(N20 P M21 P)中分离,但不再透化膜。σM对乳链菌肽抗性的主要贡献是编码应激激活的脂磷壁酸合酶的ltaSa的表达,并且σX主要通过激活控制磷壁酸的D-丙氨酰化的dlt操纵子起作用。σM和σX共同调节细胞包膜结构,以减少乳链菌肽对其脂质II靶标的接近。相比之下,σW主要涉及针对膜透化的保护,因为它几乎不提供针对乳链菌肽铰链区变体的保护。σW通过调节信号肽肽酶(SppA)、噬菌体休克蛋白(PspA和YvlC,一种PspC同系物)和亚碲酸盐抗性相关蛋白(YceGHI)而有助于乳链菌肽抗性。这些防御机制对其他羊毛硫抗生素如mersacidin、gallidermin和枯草杆菌素也有效,并且包含B的内在抗生素耐药组的重要子集。枯草芽孢杆菌
In Bacillus subtilis, the extracytoplasmic function (ECF) σ factors σM, σW, and σX all contribute to resistance against lantibiotics. Nisin, a model lantibiotic, has a dual mode of action: it inhibits cell wall synthesis by binding lipid II, and this complex also forms pores in the cytoplasmic membrane. These activities can be separated in a nisin hinge-region variant (N20P M21P) that binds lipid II, but no longer permeabilizes membranes. The major contribution of σM to nisin resistance is expression of ltaSa, encoding a stress-activated lipoteichoic acid synthase, and σX functions primarily by activation of the dlt operon controlling D-alanylation of teichoic acids. Together, σM and σX regulate cell envelope structure to decrease access of nisin to its lipid II target. In contrast, σW is principally involved in protection against membrane permeabilization as it provides little protection against the nisin hinge region variant. σW contributes to nisin resistance by regulation of a signal peptide peptidase (SppA), phage shock proteins (PspA and YvlC, a PspC homolog), and tellurite resistance related proteins (YceGHI). These defensive mechanisms are also effective against other lantibiotics such as mersacidin, gallidermin, and subtilin and comprise an important subset of the intrinsic antibiotic resistome of B. subtilis.
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