Information of MRBP isolates collected in Japan.

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鲍特菌（macrolide-resistant Bordetella pertussis, MRBP）的出现是一个严峻的公共卫生问题，因其会缩减百日咳的治疗选择，并加剧疾病的严重程度与传播范围。MRBP自2010年代起在中国大陆广泛流行，同时在其他亚洲国家偶有检出。2018年6至7月间，日本首次在东京与大阪分离得到两株MRBP临床菌株。大阪分离株BP616与东京分离株BP625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，且二者的抗菌药物敏感性谱高度相似。尽管两株菌株的检出时间重合，但始终未能明确二者之间存在可追溯的流行病学关联。本研究为进一步解析这两株分离株的遗传亲缘关系，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，两株分离株隶属于中国大陆MRBP分离株的三大进化支之一，但BP616与BP625之间存在11处单核苷酸多态性差异。基因组结构分析则显示，两株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分离株与中国大陆MRBP分离株亲缘关系密切，但基因组特征存在显著差异，提示二者系通过不同的传播途径从中国大陆传入日本。