Bce-like systems mediate resistance against antimicrobial peptides in Firmicutes bacteria. Lactobacillus casei BL23 encodes an “orphan” ABC transporter that, based on homology to BceAB-like systems, was proposed to contribute to antimicrobial peptide resistance. A mutant lacking the permease subunit was tested for sensitivity against a collection of peptides derived from bacteria, fungi, insects, and humans. Our results show that the transporter specifically conferred resistance against insect-derived cysteine-stabilized αβ defensins, and it was therefore renamed DerAB for defensin resistance ABC transporter. Surprisingly, cells lacking DerAB showed a marked increase in resistance against the lantibiotic nisin. This could be explained by significantly increased expression of the antimicrobial peptide resistance determinants regulated by the Bce-like systems PsdRSAB (formerly module 09) and ApsRSAB (formerly module 12). Bacterial two-hybrid studies in Escherichia coli showed that DerB could interact with proteins of the sensory complex in the Psd resistance system. We therefore propose that interaction of DerAB with this complex in the cell creates signaling interference and reduces the cell’s potential to mount an effective nisin resistance response. In the absence of DerB, this negative interference is relieved, leading to the observed hyperactivation of the Psd module and thus increased resistance to nisin. Our results unravel the function of a previously uncharacterized Bce-like orphan resistance transporter with pleiotropic biological effects on the cell.

中文翻译：

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干酪乳杆菌的 ABC 转运蛋白 DerAB 介导对昆虫衍生防御素的抗性。


Bce 样系统介导厚壁菌门细菌对抗菌肽的耐药性。干酪乳杆菌BL23 编码一种“孤儿”ABC 转运蛋白，基于与 BceAB 样系统的同源性，该转运蛋白被认为有助于抗菌肽耐药性。测试了缺乏通透酶亚基的突变体对来自细菌、真菌、昆虫和人类的一系列肽的敏感性。我们的结果表明，该转运蛋白特异性地赋予对昆虫来源的半胱氨酸稳定的αβ防御素的抗性，因此将其更名为DerAB，表示防御素抗性ABC转运蛋白。令人惊讶的是，缺乏 DerAB 的细胞对羊毛硫抗生素乳链菌素的抵抗力显着增加。这可以通过类 Bce 系统 PsdRSAB（以前的模块 09）和 ApsRSAB（以前的模块 12）调节的抗菌肽耐药决定簇的表达显着增加来解释。大肠杆菌中的细菌双杂交研究表明，DerB 可以与 Psd 抗性系统中感觉复合物的蛋白质相互作用。因此，我们认为 DerAB 与细胞中这种复合物的相互作用会产生信号干扰，并降低细胞产生有效乳链菌肽抵抗反应的潜力。在没有 DerB 的情况下，这种负面干扰得到缓解，导致观察到 Psd 模块过度激活，从而增加对乳链菌肽的抵抗力。我们的结果揭示了先前未表征的 Bce 样孤儿抗性转运蛋白的功能，该转运蛋白对细胞具有多效性生物效应。