福建省两地区百日咳鲍特菌抗原基因型特征及耐药性分析

doi:10.12372/jcp.2025.25e0425

临床儿科杂志 ›› 2025, Vol. 43 ›› Issue (8): 575-582.doi: 10.12372/jcp.2025.25e0425

福建省两地区百日咳鲍特菌抗原基因型特征及耐药性分析

石小松¹, 傅世杰², 何小花¹, 吕辉³, 陈厚杨², 陈茂琳⁴, 陈捷¹()

1.福州大学附属省立医院福建医科大学省立临床医学院儿科（福建福州 350001）
2.三明市尤溪县总医院儿科（福建尤溪 365100）
3.福州大学附属省立医院福建医科大学省立临床医学院检验科（福建福州 350001）
4.三明市尤溪县总医院检验科（福建尤溪 365100）

收稿日期:2025-04-21 录用日期:2025-06-18 出版日期:2025-08-15 发布日期:2025-07-28
通讯作者: 陈捷 E-mail:sy1017@fzu.edu.cn
基金资助:
三明市卫生健康科技创新联合项目;福建省西学中高级人才研修项目

Antigenic genotypic characteristics and antibiotic resistance analysis of Bordetella pertussis in two regions of Fujian province

SHI Xiaosong¹, FU Shijie², HE Xiaohua¹, LYU Hui³, CHEN Houyang², CHEN Maolin⁴, CHEN Jie¹()

1. Department of Pediatrics, Fuzhou University Affiliated Provincial Hospital, Provincial Clinical Medical College Of Fujian Medical University, Fuzhou 350001, Fujian, China
2. Department of Pediatrics, Youxi County General Hospital, Youxi 365100, Fujian, China
3. Department of Laboratory Medicine, Fuzhou University Affiliated Provincial Hospital, Provincial Clinical Medical College Of Fujian Medical University, Fuzhou 350001, Fujian, China
4. Department of Laboratory Medicine, Youxi County General Hospital, Youxi 365100, Fujian, China

Received:2025-04-21 Accepted:2025-06-18 Published:2025-08-15 Online:2025-07-28
Contact: CHEN Jie E-mail:sy1017@fzu.edu.cn

摘要/Abstract

摘要：

目的分析中国福建省福州市及尤溪县百日咳鲍特菌（BP）抗原基因多态性特征与耐药表型，为优化疫苗策略和抗菌药物使用提供科学依据。方法于2024年收集两地区336份百日咳临床疑似病例的咽拭子标本，经细菌培养、分离与鉴定后，对7个抗原基因（ptxP、ptxA、ptxC、prn、fim3、fim2、tcfA）以及23S rRNA A2047位点进行分析，以确定其多态性和变异情况。基于核心基因组单核苷酸多态性（cgSNPs）构建最大似然法系统发育树。采用E-test法检测大环内酯类、磺胺类及β-内酰胺类最低抑菌浓度（MIC）。结果 336份疑似病例咽拭子标本中成功分离出29株BP临床株（8.6%，29/336），抗原基因谱分析显示，主要流行型别为ptxP3/prn2/ptxC1/ptxA1/fim2-1/fim3-1/tcfA2（55.2%，16/29），ptxP3/prn2/ptxA1型菌株比例达72.4%（21/29），检出prn150突变株4株（13.8%）。系统发育分析表明，疫苗株CS形成了独立的进化分支（A簇），2024年福建分离株与2020年前国内菌株存在显著遗传差异，形成B（ptxP3/prn2/ptxA1，含多数福建株）和C（ptxP1/prn1/ptxA1，含既往分离株）两大进化簇。所有分离株均检测到23S rRNA A2047G突变，对大环内酯类药物的MIC>90 mg/L，呈现高度耐药；复方磺胺甲噁唑（TMP-SMX）的MIC为0.005~0.45 mg/L；β-内酰胺类（头孢曲松、头孢噻肟、头孢哌酮/舒巴坦）的MIC为0.004~0.64 mg/L。结论福建地区BP流行株呈现独特的抗原基因进化特征且存在普遍的大环内酯类耐药现象。后续需强化基于分子分型的疫苗组分监测，并结合药敏结果精准优化抗菌治疗方案。

关键词: 百日咳, 百日咳鲍特菌, 抗原基因型, 全基因组测序, 大环内酯类耐药, 儿童

Abstract:

Objective To analyze the genetic polymorphism of antigenic genes and antimicrobial resistance phenotypes of Bordetella pertussis (BP) in Fuzhou and Youxi, Fujian Province, China, and to provide scientific evidence for optimizing vaccination strategies and antibiotic use. Methods A total of 336 nasopharyngeal swab specimens from suspected pertussis cases were collected from both regions in 2024. Bacterial culture, isolation, and identification were performed. Polymorphism and mutations were determined by analyzing seven antigenic genes (ptxP, ptxA, ptxC, prn, fim3, fim2, tcfA) and the 23S rRNA A2047 locus. A maximum-likelihood phylogenetic tree was constructed based on core-genome single nucleotide polymorphisms (cgSNPs). The minimum inhibitory concentrations (MICs) of macrolides, sulfonamides, and β-lactams were determined using the E-test method. Results Twenty-nine BP clinical isolates were successfully obtained (8.6%, 29/336). Antigenic gene profiling revealed that the predominant genotype was ptxP3/prn2/ptxC1/ptxA1/fim2-1/fim3-1/tcfA2 (55.2%, 16/29), with ptxP3/prn2/ptxA1 strains accounting for 72.4% (21/29). Four prn150 mutant strains were identified (13.8%, 4/29). Phylogenetic analysis demonstrated that the vaccine strain CS formed an independent evolutionary branch (Cluster A). The 2024 Fujian isolates exhibited significant genetic divergence from pre-2020 domestic strains, forming two major clusters: Cluster B (ptxP3/prn2/ptxA1, containing most Fujian isolates) and Cluster C (ptxP1/prn1/ptxA1, comprising historical isolates). The 23S rRNA A2047G mutation conferring macrolide resistance was detected in all isolates, with MICs > 90 mg/L. MICs for TMP-SMX ranged from 0.005 to 0.45 mg/L. MICs for β-lactams (ceftriaxone, cefotaxime, cefoperazone/sulbactam) ranged from 0.004 to 0.64 mg/L. Conclusion The epidemic strains of BP circulating in Fujian exhibit distinct antigenic gene evolutionary patterns and widespread macrolide resistance. These findings highlight the urgent need to strengthen molecular genotyping-based surveillance of vaccine components and optimize antimicrobial therapy based on susceptibility profiles.

Key words: pertussis, Bordetella pertussis, antigenic genotype, whole-genome sequencing, macrolide resistance, child

中图分类号:

石小松, 傅世杰, 何小花, 吕辉, 陈厚杨, 陈茂琳, 陈捷. 福建省两地区百日咳鲍特菌抗原基因型特征及耐药性分析[J]. 临床儿科杂志, 2025, 43(8): 575-582.

SHI Xiaosong, FU Shijie, HE Xiaohua, LYU Hui, CHEN Houyang, CHEN Maolin, CHEN Jie. Antigenic genotypic characteristics and antibiotic resistance analysis of Bordetella pertussis in two regions of Fujian province[J]. Journal of Clinical Pediatrics, 2025, 43(8): 575-582.

图/表 3

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基因型	菌株编号	总计n（%）
ptxP3/prn2/ptxC1/ptxA1/fim2-1/fim3-1/tcfA2	Fujian_8、9、10、11、13、14、15、17、20、21、22、23、24、25、26、27	16（55.2）
ptxP3/prn2/ptxC2/ptxA1/fim2-1/fim3-1/tcfA2	Fujian_2、3、5、6、7	5（17.2）
ptxP1/prn1/ptxC1/ptxA1/fim2-1/fim3-1/tcfA2	Fujian_12、16、18、19	4（13.8）
ptxP3/prn150/ptxC1/ptxA1/fim2-1/fim3-1/tcfA2	Fujian_28、29	2（6.9）
ptxP3/prn150/ptxC2/ptxA1/ fim2-1/fim3-3/tcfA2	Fujian_1、4	2（6.9）

抗菌药物	MIC范围/mg·L^-1	MIC₅₀/mg·L^-1	MIC₉₀/mg·L^-1
红霉素	>256	>256	>256
阿奇霉素	90~>256	120	>256
克拉霉素	>256	>256	>256
复方磺胺甲噁唑	0.005~0.45	0.15	0.30
头孢曲松	0.012~0.64	0.064	0.12
头孢噻肟	0.004~0.40	0.014	0.40
头孢哌酮/舒巴坦	0.02~0.12	0.042	0.082

福建省两地区百日咳鲍特菌抗原基因型特征及耐药性分析

Antigenic genotypic characteristics and antibiotic resistance analysis of Bordetella pertussis in two regions of Fujian province

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