Ultrastructural, metabolic and genetic characteristics of determinants facilitating the acquisition of macrolide resistance by Streptococcus pneumoniae

IF 15.8 1区 医学 Q1 PHARMACOLOGY & PHARMACY
Xueqing Wu , Babek Alibayov , Xi Xiang , Santiago M. Lattar , Fuminori Sakai , Austin A. Medders , Brenda S. Antezana , Lance E. Keller , Ana G.J. Vidal , Yih-Ling Tzeng , D. Ashley Robinson , David S. Stephens , Yunsong Yu , Jorge E. Vidal
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引用次数: 0

Abstract

Aims

To investigate the molecular events associated with acquiring macrolide resistance genes [mefE/mel (Mega) or ermB] in Streptococcus pneumoniae (Spn) during nasopharyngeal colonization.

Methods and results

Genomic analysis of 128 macrolide-resistant Spn isolates revealed recombination events in genes of the conjugation apparatus, or the competence system, in strains carrying Tn916-related elements. Studies using confocal and electron microscopy demonstrated that during the transfer of Tn916-related elements in nasopharyngeal cell biofilms, pneumococcal strains formed clusters facilitating their acquisition of resistance determinants at a high recombination frequency (rF). Remarkably, these aggregates comprise both encapsulated and nonencapsulated pneumococci that span extracellular and intracellular compartments. rF assessments showed similar rates regardless Mega was associated with large integrative and conjugative elements (ICEs) (>23 kb) or not (∼5.4 kb). The rF for Mega Class IV(c) insertion region (∼53 kb) was three orders of magnitude higher than the transformation of the capsule locus. Metabolomics studies of the microenvironment created by colonization of human nasopharyngeal cells revealed a link between the acquisition of ICEs and the pathways involving nicotinic acid and sucrose.

Conclusions

Pneumococcal clusters, both extracellular and intracellular, facilitate macrolide resistance acquisition, and ICEs were acquired at a higher frequency than the capsule locus. Metabolic changes could serve as intervention targets.

促进肺炎链球菌获得大环内酯耐药性的决定因素的超微结构、代谢和遗传特征
目的研究肺炎链球菌(Spn)在鼻咽部定植过程中获得大环内酯耐药基因[mefE/mel(Mega)或ermB]的相关分子事件。方法和结果对128株耐大环内酯的Spn分离株进行基因组分析,发现在携带Tn916相关元件的菌株中,共轭装置或能力系统的基因发生了重组事件。使用共聚焦显微镜和电子显微镜进行的研究表明,在鼻咽细胞生物膜中转移 Tn916 相关元素的过程中,肺炎球菌菌株会形成聚集体,从而以较高的重组频率(rF)获得抗性决定因子。无论 Mega 是否与大型整合与共轭元件(ICEs)(23 kb)有关(5.4 kb),rF 评估都显示出相似的比率。Mega IV(c)类插入区域(∼53 kb)的rF比囊状基因座的转化率高三个数量级。对人类鼻咽细胞定植所产生的微环境进行的代谢组学研究发现,获得 ICEs 与涉及烟酸和蔗糖的途径之间存在联系。代谢变化可作为干预目标。
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来源期刊
Drug Resistance Updates
Drug Resistance Updates 医学-药学
CiteScore
26.20
自引率
11.90%
发文量
32
审稿时长
29 days
期刊介绍: Drug Resistance Updates serves as a platform for publishing original research, commentary, and expert reviews on significant advancements in drug resistance related to infectious diseases and cancer. It encompasses diverse disciplines such as molecular biology, biochemistry, cell biology, pharmacology, microbiology, preclinical therapeutics, oncology, and clinical medicine. The journal addresses both basic research and clinical aspects of drug resistance, providing insights into novel drugs and strategies to overcome resistance. Original research articles are welcomed, and review articles are authored by leaders in the field by invitation. Articles are written by leaders in the field, in response to an invitation from the Editors, and are peer-reviewed prior to publication. Articles are clear, readable, and up-to-date, suitable for a multidisciplinary readership and include schematic diagrams and other illustrations conveying the major points of the article. The goal is to highlight recent areas of growth and put them in perspective. *Expert reviews in clinical and basic drug resistance research in oncology and infectious disease *Describes emerging technologies and therapies, particularly those that overcome drug resistance *Emphasises common themes in microbial and cancer research
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