General genome features of Japanese MRBP.

The emergence of macrolide-resistant Bordetella pertussis (MRBP) is a significant problem because it reduces treatment options for pertussis and exacerbates the severity and spread of the disease. MRBP has been widely prevalent in mainland China since the 2010s and has been sporadically detected in other Asian countries. In Japan, two MRBP clinical strains were first isolated in Tokyo and Osaka between June and July 2018. The isolates BP616 in Osaka and BP625 in Tokyo harbored the same virulence-associated allelic genes (including ptxP1, ptxA1, prn1, fim3A, and fhaB3) and MT195 genotype and exhibited similar antimicrobial susceptibility profiles. However, despite their simultaneous occurrence, a distinguishable epidemiological link between these isolates could not be established. To gain further insight into the genetic relationship between these isolates in this study, we performed whole-genome analyses. Phylogenetic analysis based on genome-wide single-nucleotide polymorphisms revealed that the isolates belonged to one of the three clades of Chinese MRBP isolates, but there were 11 single-nucleotide polymorphism differences between BP616 and BP625. Genome structure analysis revealed two large inversions (202 and 523 kbp) and one small transposition (3.8 kbp) between the genomes. These findings indicate that the two Japanese MRBP isolates are closely related to Chinese MRBP isolates but are genomically distinct, suggesting that they were introduced into Japan from mainland China through different transmission routes.大环内酯类耐药百日咳博德特菌（macrolide-resistant Bordetella pertussis, MRBP）的出现是一项亟待关注的公共卫生难题，因其会缩减百日咳的临床治疗选择，并加剧疾病的严重程度与传播范围。自2010年代起，MRBP在中国大陆已广泛流行，同时在其他亚洲国家亦偶有检出。2018年6至7月间，日本首次在东京与大阪两地分离到两株MRBP临床菌株，分别为大阪株BP616与东京株BP625。上述两菌株携带完全一致的毒力相关等位基因（包括ptxP1、ptxA1、prn1、fim3A与fhaB3）以及MT195基因型，且抗菌药物敏感性谱高度相似。然而，尽管两株菌株同期被检出，研究人员仍未能确立二者之间可追溯的流行病学关联。为深入解析这两株菌株的遗传亲缘关系，本研究开展了全基因组分析。基于全基因组单核苷酸多态性的系统发育分析结果显示，两株菌株隶属于中国MRBP分离株的三大进化分支之一，但BP616与BP625之间存在11处单核苷酸多态性差异。基因组结构分析则揭示，两菌株的基因组之间存在两处大片段倒位（分别为202 kbp与523 kbp）以及一处小片段转位（3.8 kbp）。上述研究结果表明，这两株日本MRBP分离株与中国MRBP分离株亲缘关系密切，但在基因组层面存在显著差异，提示二者通过不同的传播途径从中国大陆传入日本。