What Does the Talking?: Quorum Sensing Signalling Genes Discovered in a Bacteriophage Genome

The transfer of novel genetic material into the genomes of bacterial viruses (phages) has been widely documented in several host-phage systems. Bacterial genes are incorporated into the phage genome and, if retained, subsequently evolve within them. The expression of these phage genes can subvert or bolster bacterial processes, including altering bacterial pathogenicity. The phage phiCDHM1 infects Clostridium difficile, a pathogenic bacterium that causes nosocomial infections and is associated with antibiotic treatment. Genome sequencing and annotation of phiCDHM1 shows that despite being closely related to other C. difficile myoviruses, it has several genes that have not been previously reported in any phage genomes. Notably, these include three homologs of bacterial genes from the accessory gene regulator (agr) quorum sensing (QS) system. These are; a pre-peptide (AgrD) of an autoinducing peptide (AIP), an enzyme which processes the pre-peptide (AgrB) and a histidine kinase (AgrC) that detects the AIP to activate a response regulator. Phylogenetic analysis of the phage and C. difficile agr genes revealed that there are three types of agr loci in this species. We propose that the phage genes belonging to a third type, agr3, and have been horizontally transferred from the host. AgrB and AgrC are transcribed during the infection of two different strains. In addition, the phage agrC appears not to be confined to the phiCDHM1 genome as it was detected in genetically distinct C. difficile strains. The discovery of QS gene homologs in a phage genome presents a novel way in which phages could influence their bacterial hosts, or neighbouring bacterial populations. This is the first time that these QS genes have been reported in a phage genome and their distribution both in C. difficile and phage genomes suggests that the agr3 locus undergoes horizontal gene transfer within this species.

将新型遗传物质导入细菌病毒（噬菌体，phages）基因组的现象，已在多种宿主-噬菌体系统中被广泛报道。细菌基因可整合进入噬菌体基因组，若得以保留，则会在噬菌体基因组内持续演化。此类噬菌体基因的表达可颠覆或增强细菌的生理过程，包括改变细菌的致病性。噬菌体phiCDHM1可感染艰难梭菌（Clostridium difficile），后者是一类可引发医院感染且与抗生素治疗相关的致病性细菌。对phiCDHM1进行基因组测序与注释后发现，尽管其与其他艰难梭菌肌尾噬菌体（myoviruses）亲缘关系紧密，但它携带有若干此前未在任何噬菌体基因组中报道过的基因。值得注意的是，其中包含三类来自细菌附属基因调节（accessory gene regulator，agr）群体感应（quorum sensing，QS）系统的同源基因，具体包括：自诱导肽（autoinducing peptide，AIP）的前体肽（AgrD）、加工该前体肽的酶（AgrB），以及检测自诱导肽以激活应答调控蛋白的组氨酸激酶（AgrC）。对噬菌体与艰难梭菌的agr基因进行系统发育分析后发现，该物种中存在三类agr基因座（loci）。我们推测，属于第三类agr3的噬菌体基因是从宿主中水平转移获得的。在感染两种不同菌株的过程中，agrB与agrC均会被转录。此外，噬菌体agrC基因并非仅局限于phiCDHM1基因组中，在遗传背景各异的艰难梭菌菌株中也可检测到该基因。在噬菌体基因组中发现群体感应基因同源物，为噬菌体影响其细菌宿主或邻近细菌种群提供了一种全新的途径。这是首次在噬菌体基因组中报道此类群体感应基因，且它们在艰难梭菌与噬菌体基因组中的分布特征表明，agr3基因座可在该物种内部发生水平基因转移。