Genomic epidemiology of erythromycin-resistant Bordetella pertussis in China
Genomic epidemiology of erythromycin-resistant Bordetella pertussis in China
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中国耐红霉素百日咳博德特氏菌的基因组流行病学
DOI：
10.1080/22221751.2019.1587315
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发表时间：
2019-03-22
影响因子：
13.2
通讯作者：
Lan, Ruiting
中科院分区：
文献类型：
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作者：
Xu, Zheng;Wang, Zengguo;Lan, Ruiting
大环内酯类药物如红霉素是治疗百日咳杆菌感染的经验性药物。自2013年首次报道耐红霉素百日咳分离株以来，中国的百日咳分离株数量有所增加。在此，我们对2012 - 2015年中国百日咳分离株进行了基因组研究，以阐明中国红霉素耐药百日咳分离株的起源和系统发育关系。采用167株中国百日咳分离株进行抗生素敏感性试验和多位点可变数串联重复（VNTR）分析（MLVA）。除4株红霉素耐药外，其余4株红霉素敏感株均为非ptxp1。MLVA型（MT）、MT55型、MT104型和MT195型为主要类型。其中50株进行了全基因组测序和系统发育分析。基因组测序和系统发育分析显示三个独立的红霉素耐药谱系，所有耐药菌株都携带23S rRNA基因突变。在中国ptxP1分离株中发现了一个新的fhaB3等位基因，这些中国ptxP1- ptxa1 -fhaB3的突变率比全球ptxP1- ptxa1百日咳人群高5倍。我们的结果表明，中国百日咳的进化可能是由疫苗接种和抗生素的选择压力驱动的。在中国百日咳人群中出现新的非疫苗fhaB3等位基因可能是疫苗选择的结果，而ptxP1-fhaB3谱系的扩增很可能是抗生素选择压力的结果。为了更好地了解病原体的演变，需要进一步监测中国的百日咳双歧杆菌。
ABSTRACT Macrolides such as erythromycin are the empirical treatment of Bordetella pertussis infections. China has experienced an increase in erythromycin-resistant B. pertussis isolates since they were first reported in 2013. Here, we undertook a genomic study on Chinese B. pertussis isolates from 2012 to 2015 to elucidate the origins and phylogenetic relationships of erythromycin-resistant B. pertussis isolates in China. A total of 167 Chinese B. pertussis isolates were used for antibiotic sensitivity testing and multiple locus variable-number tandem repeat (VNTR) analysis (MLVA). All except four isolates were erythromycin-resistant and of the four erythromycin-sensitive isolates, three were non-ptxP1. MLVA types (MT), MT55, MT104 and MT195 were the predominant types. Fifty of those isolates were used for whole genome sequencing and phylogenetic analysis. Genome sequencing and phylogenetic analysis revealed three independent erythromycin-resistant lineages and all resistant isolates carried a mutation in the 23S rRNA gene. A novel fhaB3 allele was found uniquely in Chinese ptxP1 isolates and these Chinese ptxP1-ptxA1-fhaB3 had a 5-fold higher mutation rate than the global ptxP1-ptxA1 B. pertussis population. Our results suggest that the evolution of Chinese B. pertussis is likely to be driven by selection pressure from both vaccination and antibiotics. The emergence of the new non-vaccine fhaB3 allele in Chinese B. pertussis population may be a result of selection from vaccination, whereas the expansion of ptxP1-fhaB3 lineages was most likely to be the result of selection pressure from antibiotics. Further monitoring of B. pertussis in China is required to better understand the evolution of the pathogen.