Vasieva O, Goryanin I
University of Liverpool, Crown street, Liverpool, UK.
Ingenet ltd, 3d floor, 207 Regent street, London, UK.
J Integr Bioinform. 2019 Jul 13;16(4):20190016. doi: 10.1515/jib-2019-0016.
Functional coupling and comparative genomics analysis have been applied to study functional associations of orthologs of enterococcal cAD1 sex pheromone (P13268) known to be responsible for biofilm formation, conjugative plasmid transfer and spreading of bacterial antibiotics resistance. cAD1 peptide pheromone is released from the membrane lipoprotein with the peptide precursor encoded by a gene cad (tr|C2JQE7). Our analysis of genomic neighbourhood of cad and motifs of the encoded polypeptide and its orthologs suggests a close functional association between cAD1 and ApbE protein (Q82Z24), a FMN insertion and trafficking facilitator. The cad and apbE orthologs were coupled in the genomes and ApbE-specific motifs for FMN covalent attachment were identified in cad-encoded protein sequence and its orthologs. These findings suggest a potential role of FMN-based reductase function of the cAD1 lipoprotein precursor in its processing and release of the active sex pheromone peptide. They may lead to a new approach in prevention of antibiotic resistance spread via targeting sex pheromone processing chaperones or by suppression of the FMN availability and covalent binding. This methods can be also applied to a controlled evolution of bacterial pathogenicity in microbial fuel cells, as the findings suggest the crosstalk between bacterial pathogenicity and bacterial electro-activity.
功能偶联和比较基因组学分析已被用于研究肠球菌cAD1性信息素(P13268)的直系同源物的功能关联,已知该信息素负责生物膜形成、接合质粒转移和细菌抗生素抗性的传播。cAD1肽信息素从膜脂蛋白中释放出来,其肽前体由基因cad(tr|C2JQE7)编码。我们对cad的基因组邻域以及编码多肽及其直系同源物的基序的分析表明,cAD1与ApbE蛋白(Q82Z24)之间存在密切的功能关联,ApbE蛋白是一种FMN插入和转运促进因子。cad和apbE的直系同源物在基因组中偶联,并且在cad编码的蛋白质序列及其直系同源物中鉴定出了用于FMN共价连接的ApbE特异性基序。这些发现表明,cAD1脂蛋白前体基于FMN的还原酶功能在其活性性信息素肽的加工和释放中可能发挥作用。它们可能会导致一种新的方法来预防抗生素抗性的传播,即通过靶向性信息素加工伴侣或抑制FMN的可用性和共价结合。由于这些发现表明细菌致病性与细菌电活性之间存在相互作用,因此该方法也可应用于微生物燃料电池中细菌致病性的可控进化。