Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, UK.
Republican Research and Practical Centre for Epidemiology and Microbiology, Minsk, Republic of Belarus.
BMC Genomics. 2017 Nov 13;18(1):873. doi: 10.1186/s12864-017-4276-3.
Diphtheria remains a major public health concern with multiple recent outbreaks around the world. Moreover, invasive non-toxigenic strains have emerged globally causing severe infections. A diphtheria epidemic in the former Soviet Union in the 1990s resulted in ~5000 deaths. In this study, we analysed the genome sequences of a collection of 93 C. diphtheriae strains collected during and after this outbreak (1996 - 2014) in a former Soviet State, Belarus to understand the evolutionary dynamics and virulence capacities of these strains.
C. diphtheriae strains from Belarus belong to ten sequence types (STs). Two major clones, non-toxigenic ST5 and toxigenic ST8, encompassed 76% of the isolates that are associated with sore throat and diphtheria in patients, respectively. Core genomic diversity is limited within outbreak-associated ST8 with relatively higher mutation rates (8.9 × 10 substitutions per strain per year) than ST5 (5.6 × 10 substitutions per strain per year) where most of the diversity was introduced by recombination. A variation in the virulence gene repertoire including the presence of tox gene is likely responsible for pathogenic differences between different strains. However, strains with similar virulence potential can cause disease in some individuals and remain asymptomatic in others. Eight synonymous single nucleotide polymorphisms were observed between the tox genes of the vaccine strain PW8 and other toxigenic strains of ST8, ST25, ST28, ST41 and non-toxigenic tox gene-bearing (NTTB) ST40 strains. A single nucleotide deletion at position 52 in the tox gene resulted in the frameshift in ST40 isolates, converting them into NTTB strains.
Non-toxigenic C. diphtheriae ST5 and toxigenic ST8 strains have been endemic in Belarus both during and after the epidemic in 1990s. A high vaccine coverage has effectively controlled diphtheria in Belarus; however, non-toxigenic strains continue to circulate in the population. Recombination is an important evolutionary force in shaping the genomic diversity in C. diphtheriae. However, the relative role of recombination and mutations in diversification varies between different clones.
白喉仍是一个重大的公共卫生关注点，在世界范围内近期有多起暴发。此外，具有侵袭性的非产毒株已在全球范围内出现，导致严重感染。20 世纪 90 年代前苏联发生的白喉疫情导致约 5000 人死亡。在本研究中，我们分析了在白俄罗斯一个前苏联国家收集的 93 株 C. diphtheriae 菌株的基因组序列，这些菌株是在该暴发期间（1996-2014 年）和之后收集的，以了解这些菌株的进化动态和毒力能力。
白俄罗斯的 C. diphtheriae 菌株属于 10 个序列型（ST）。两个主要克隆，非产毒株 ST5 和产毒株 ST8，分别涵盖了与患者咽痛和白喉相关的 76%的分离株。与暴发相关的 ST8 的核心基因组多样性有限，其突变率相对较高（每年每株 8.9×10 个替换），而 ST5 的突变率较低（每年每株 5.6×10 个替换），其中大部分多样性是由重组引入的。毒力基因谱的变化，包括毒基因的存在，可能是不同菌株之间致病性差异的原因。然而，具有相似毒力潜力的菌株可以在某些个体中引起疾病，而在其他个体中则无症状。在疫苗株 PW8 的毒基因和其他 ST8、ST25、ST28、ST41 产毒株和非产毒基因携带（NTTB）ST40 株的毒基因之间观察到 8 个同义单核苷酸多态性。毒基因第 52 位的单个核苷酸缺失导致 ST40 分离株发生移码，将其转化为 NTTB 株。
非产毒株 C. diphtheriae ST5 和产毒株 ST8 菌株在 20 世纪 90 年代的疫情期间和之后一直在白俄罗斯流行。高疫苗覆盖率有效地控制了白喉在白俄罗斯的流行；然而，非产毒株仍在人群中传播。重组是塑造 C. diphtheriae 基因组多样性的重要进化力量。然而，重组和突变在不同克隆中的多样化作用有所不同。
