Goldbeck Oliver, Weixler Dominik, Eikmanns Bernhard J, Riedel Christian U
Institute of Microbiology and Biotechnology, Ulm University, 89081 Ulm, Germany.
Microorganisms. 2021 Mar 19;9(3):646. doi: 10.3390/microorganisms9030646.
Post-translationally modified, (methyl-)lanthionine-containing peptides are produced by several Gram-positive bacteria. These so-called lantibiotics have potent activity against various bacterial pathogens including multidrug-resistant strains and are thus discussed as alternatives to antibiotics. Several naturally occurring mechanisms of resistance against lantibiotics have been described for bacteria, including cell envelope modifications, ABC-transporters, lipoproteins and peptidases. species are widespread in nature and comprise important pathogens, commensals as well as environmentally and biotechnologically relevant species. Yet, little is known about lantibiotic biosynthesis and resistance in this genus. Here, we present a comprehensive in silico prediction of lantibiotic resistance traits in this important group of Gram-positive bacteria. Our analyses suggest that enzymes for cell envelope modification, peptidases as well as ABC-transporters involved in peptide resistance are widely distributed in the genus. Based on our predictions, we analyzed the susceptibility of six species to nisin and found that those without dedicated resistance traits are more susceptible and unable to adapt to higher concentrations. In addition, we were able to identify lantibiotic resistance operons encoding for peptidases, ABC-transporters and two-component systems with an unusual predicted structure that are conserved in the genus . Heterologous expression shows that these operons indeed confer resistance to the lantibiotic nisin.
几种革兰氏阳性细菌可产生翻译后修饰的含（甲基）羊毛硫氨酸的肽。这些所谓的羊毛硫抗生素对包括多重耐药菌株在内的各种细菌病原体具有强大的活性，因此被视为抗生素的替代品。已描述了细菌对羊毛硫抗生素的几种天然耐药机制，包括细胞壁修饰、ABC转运蛋白、脂蛋白和肽酶。[具体细菌名称]在自然界广泛分布，包括重要的病原体、共生菌以及与环境和生物技术相关的物种。然而，关于该属中羊毛硫抗生素的生物合成和耐药性知之甚少。在此，我们对这一重要的革兰氏阳性细菌群体中的羊毛硫抗生素耐药特性进行了全面的计算机预测。我们的分析表明，参与肽抗性的细胞壁修饰酶、肽酶以及ABC转运蛋白在该属中广泛分布。基于我们的预测，我们分析了六种[具体细菌名称]对乳链菌肽的敏感性，发现那些没有专门耐药特性的菌株更易受影响，且无法适应更高浓度。此外，我们能够鉴定出编码肽酶、ABC转运蛋白和具有异常预测结构的双组分系统的羊毛硫抗生素耐药操纵子，这些操纵子在[具体细菌名称]属中是保守的。异源表达表明这些操纵子确实赋予了对羊毛硫抗生素乳链菌肽的抗性。
