Department of Genetics and Genome Biology, University of Leicester, Leicester, UK.
Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK.
Microb Genom. 2020 May;6(5). doi: 10.1099/mgen.0.000367. Epub 2020 Apr 29.
is a Gram-negative human commensal pathogen, with extensive phenotypic plasticity afforded by phase-variable (PV) gene expression. Phase variation is a stochastic switch in gene expression from an ON to an OFF state, mediated by localized hypermutation of simple sequence repeats (SSRs). Circulating clones vary in propensity to cause disease, with some clonal complexes (ccs) classified as hypervirulent and others as carriage-associated. We examined the PV gene repertoires, or phasome, of these lineages in order to determine whether phase variation contributes to disease propensity. We analysed 3328 genomes representative of nine circulating meningococcal ccs with Phasome, a tool that identifies PV genes by the presence of SSRs and homologous gene clusters. The presence, absence and functions of all identified PV gene clusters were confirmed by annotation or blast searches within the PubMLST database. While no significant differences were detected in the number of PV genes or the core, conserved phasome content between hypervirulent and carriage lineages, individual ccs exhibited major variations in PV gene numbers. Phylogenetic clusters produced by phasome or core genome analyses were similar, indicating co-evolution of PV genes with the core genome. While conservation of PV clusters is high, with 76 % present in all meningococcal isolates, maintenance of an SSR is variable, ranging from conserved in all isolates to present only in a single cc, indicating differing evolutionary trajectories for each lineage. Diverse functional groups of PV genes were present across the meningococcal lineages; however, the majority directly or indirectly influence bacterial surface antigens and could impact on future vaccine development. Finally, we observe that meningococci have open pan phasomes, indicating ongoing evolution of PV gene content and a significant potential for adaptive changes in this clinically relevant genus.
脑膜炎奈瑟菌是一种革兰氏阴性的人类共生病原体，具有广泛的表型可塑性，这得益于其相位可变（PV）基因表达。相位变更是一种基因表达从“开”到“关”的随机开关，由简单重复序列（SSR）的局部超突变介导。循环克隆在引起疾病的倾向上有所不同，一些克隆复合体（cc）被归类为高毒力，而另一些则与携带相关。我们研究了这些谱系的 PV 基因库或相体，以确定相位变化是否有助于疾病倾向。我们分析了 3328 个代表九个循环脑膜炎奈瑟菌 cc 的基因组，Phasome 是一种通过 SSR 和同源基因簇来识别 PV 基因的工具。通过 PubMLST 数据库中的注释或blast 搜索，确认了所有鉴定的 PV 基因簇的存在、缺失和功能。虽然在高毒力和携带谱系之间，PV 基因的数量或核心、保守相体内容没有发现显著差异，但个别 cc 显示出 PV 基因数量的重大变化。由相体或核心基因组分析产生的系统发育聚类相似，表明 PV 基因与核心基因组的共同进化。虽然 PV 簇的保守性很高，76%存在于所有脑膜炎奈瑟菌分离株中，但 SSR 的维持是可变的，从所有分离株中都存在到仅存在于单个 cc 中，表明每个谱系的进化轨迹不同。脑膜炎奈瑟菌谱系中存在多种功能的 PV 基因群；然而，大多数直接或间接影响细菌表面抗原，可能影响未来疫苗的开发。最后，我们观察到脑膜炎奈瑟菌具有开放的泛相体，表明 PV 基因内容的持续进化和在这个临床相关属中发生适应性变化的巨大潜力。
