Centre for Infectious Diseases and Microbiology-Public Health, Westmead Hospital, Westmead, New South Wales, Australia.
Neilan Laboratory of Microbial and Molecular Diversity, College of Engineering, Science and Environment, The University of Newcastle, Newcastle, New South Wales, Australia.
J Antimicrob Chemother. 2022 Oct 28;77(11):3016-3025. doi: 10.1093/jac/dkac272.
The emergence of macrolide resistance in Bordetella pertussis, the causative agent of pertussis, due to mutations in the 23S rRNA gene has been recently recognized. However, resistance mechanisms to macrolides in Bordetella parapertussis and Bordetella holmesii remain unknown.
This study investigated genomic changes induced by in vitro exposure to erythromycin in these three main pathogens responsible for pertussis-like disease.
A set of 10 clinical and reference strains of B. pertussis, B. parapertussis and B. holmesii was exposed to erythromycin for 15 weeks or 30 subculture passages. Antibiotic pressure was achieved by growth on the selective media with erythromycin Etest strips or impregnated discs. Genome polymorphisms and transcriptomic profiles were examined by short- and long-read sequencing of passaged isolates.
B. parapertussis and B. holmesii isolates developed significant in vitro resistance to erythromycin (MIC >256 mg/L) within 2 to 7 weeks and at 5 to 12 weeks, respectively. B. pertussis remained phenotypically susceptible to the antibiotic following 15 weeks of exposure, with the MIC between 0.032 to 0.38 mg/L. Genomic analysis revealed that B. holmesii developed resistance due to mutations in the 23S rRNA gene. The resistance mechanism in B. parapertussis was hypothesized as being due to upregulation of an efflux pump mechanism.
These findings indicate that both B. holmesii and B. parapertussis can be more prone to induced resistance following exposure to treatment with erythromycin than B. pertussis. The surveillance of macrolide resistance in Bordetella isolates recovered from patients with pertussis, especially persistent disease, is warranted.
最近发现，由于 23S rRNA 基因突变，导致百日咳博德特氏菌（百日咳的病原体）对大环内酯类药物产生耐药性。然而，副百日咳博德特氏菌和霍氏博德特氏菌对大环内酯类药物的耐药机制仍不清楚。
本研究旨在研究这三种主要的百日咳样疾病病原体在体外暴露于红霉素后诱导的基因组变化。
一组 10 株临床和参考株的百日咳博德特氏菌、副百日咳博德特氏菌和霍氏博德特氏菌暴露于红霉素中 15 周或 30 次传代培养。通过在含有红霉素 Etest 条或浸渍盘的选择性培养基上生长来实现抗生素压力。通过对传代分离株进行短读和长读测序来检测基因组多态性和转录组谱。
副百日咳博德特氏菌和霍氏博德特氏菌在 2 至 7 周和 5 至 12 周内分别对红霉素（MIC > 256mg/L）产生了显著的体外耐药性。在暴露 15 周后，百日咳博德特氏菌对该抗生素仍表现出表型敏感性，MIC 值在 0.032 至 0.38mg/L 之间。基因组分析显示，霍氏博德特氏菌的耐药性是由于 23S rRNA 基因的突变引起的。副百日咳博德特氏菌的耐药机制推测是由于外排泵机制的上调。
这些发现表明，与百日咳博德特氏菌相比，副百日咳博德特氏菌和霍氏博德特氏菌在暴露于红霉素治疗后更容易产生诱导性耐药。有必要对从百日咳患者（尤其是持续性疾病患者）中分离出的博德特氏菌分离物的大环内酯类药物耐药性进行监测。
