Centre for Cell Factories and Biopolymers, Griffith Institute for Drug Discovery, Griffith University, Nathan, Australia.
BMC Microbiol. 2020 Apr 6;20(1):77. doi: 10.1186/s12866-020-01772-0.
Circular bacteriocins are antimicrobial peptides produced by bacteria with a N and C termini ligation. They have desirable properties such as activity at low concentrations along with thermal, pH and proteolytic resistance. There are twenty experimentally confirmed circular bacteriocins as part of bacteriocin gene clusters, with transport, membrane and immunity proteins. Traditionally, novel antimicrobials are found by testing large numbers of isolates against indicator strains, with no promise of corresponding novel sequence.
Through bioprospecting publicly available sequence databases, we identified ninety-nine circular bacteriocins across a variety of bacteria bringing the total to 119. They were grouped into two families within class I modified bacteriocins (i and ii) and further divided into subfamilies based on similarity to experimentally confirmed circular bacteriocins. Within subfamilies, sequences overwhelmingly shared similar characteristics such as sequence length, presence of a polybasic region, conserved locations of aromatic residues, C and N termini, gene clusters similarity, translational coupling and hydrophobicity profiles. At least ninety were predicted to be putatively functional based on gene clusters. Furthermore, bacteriocins identified from Enterococcus, Staphylococcus and Streptococcus species may have activity against clinically relevant strains, due to the presence of putative immunity genes required for expression in a toxin-antitoxin system. Some strains such as Paenibacillus larvae subsp. pulvifaciens SAG 10367 contained multiple circular bacteriocin gene clusters from different subfamilies, while some strains such as Bacillus cereus BCE-01 contained clusters with multiple circular bacteriocin structural genes.
Sequence analysis provided rapid insight into identification of novel, putative circular bacteriocins, as well as conserved genes likely essential for circularisation. This represents an expanded library of putative antimicrobial proteins which are potentially active against human, plant and animal pathogens.
环状细菌素是一类由细菌产生的具有 N 端和 C 端连接的抗菌肽。它们具有许多理想的特性，例如在低浓度下具有活性，同时具有热稳定性、耐酸碱性和抗蛋白酶水解性。目前已经有二十种经过实验证实的环状细菌素作为细菌素基因簇的一部分，其中包括转运蛋白、膜蛋白和免疫蛋白。传统上，通过测试大量分离株对抗指示菌株来寻找新型抗菌药物，这并不能保证有相应的新型序列。
通过对公共可用序列数据库进行生物勘探，我们在各种细菌中鉴定出了 99 种环状细菌素，使总数达到 119 种。它们被分为 I 类修饰细菌素（i 和 ii）的两个家族，并根据与实验证实的环状细菌素的相似性进一步分为亚家族。在亚家族中，序列绝大多数具有相似的特征，如序列长度、多碱性区域的存在、芳香族残基的保守位置、C 端和 N 端、基因簇相似性、翻译偶联和疏水性谱。至少 90 个基于基因簇被预测为具有潜在功能。此外，由于存在表达毒素-抗毒素系统所需的假定免疫基因，来自肠球菌、葡萄球菌和链球菌属的细菌素可能对临床相关菌株具有活性。一些菌株，如 Pulvifaciens 亚种 Paenibacillus larvae SAG 10367，含有来自不同亚家族的多个环状细菌素基因簇，而一些菌株，如 Bacillus cereus BCE-01，则含有具有多个环状细菌素结构基因的基因簇。
序列分析为快速鉴定新型潜在环状细菌素以及可能对环状化至关重要的保守基因提供了快速的思路。这代表了一个潜在的抗菌蛋白扩展库，这些蛋白可能对人类、植物和动物病原体具有活性。
