Genomic and phenotypic characterization of antimicrobial resistance in clinical Nocardia species isolates.

IF 4.8 2区 医学 Q2 IMMUNOLOGY
Frontiers in Cellular and Infection Microbiology Pub Date : 2025-09-18 eCollection Date: 2025-01-01 DOI:10.3389/fcimb.2025.1672889
Ziyu Song, Bingqian Du, Min Yuan, Jirao Shen, Shuai Xu, Wanchun Guan, Binghuai Lu, Zhenjun Li
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引用次数: 0

Abstract

Background: Antimicrobial resistance is prevalent across Nocardia species, with varying resistance profiles among different species, which poses significant challenges to effective treatment strategies. Our study aimed to assess the antimicrobial susceptibility profiles of various Nocardia species and investigate the potential correlation between resistance phenotypes and their underlying genotypes.

Methods: This study analyzed 148 clinical Nocardia isolates from 13 provinces in China. Minimum inhibitory concentrations (MICs) for 15 antimicrobial agents were determined using the microbroth dilution method. Whole genome sequencing (WGS) was performed for all isolates, followed by bioinformatics analyses integrated with 70 human-sourced Nocardia genomes in the National Center for Biotechnology Information (NCBI), encompassing species verification, phylogenetic analysis, and the identification of antimicrobial resistance genes (ARGs).

Results: Average Nucleotide Identity (ANI) analysis reclassified several misidentified isolates and revealed 14 potentially novel Nocardia species, underscoring the taxonomic complexity within this genus. Nocardia species exhibited distinct resistance profiles: Nocardia farcinica demonstrated elevated resistance to cephalosporins and tobramycin; Nocardia otitidiscaviarum showed broad resistance to β-lactams and quinolones; and Nocardia cyriacigeorgica exhibited resistance to quinolones, cefepime, and cefoxitin. Notably, clarithromycin resistance was consistently high across all species. Moreover, 38.51% of Nocardia isolates are resistant to two or more commonly used antibiotics, which revealed widespread multidrug resistance (MDR). Strong genotype-phenotype correlations were observed, including sul1 in sulfamethoxazole/trimethoprim-resistant N. farcinica, bla AST-1 in β-lactam-resistant N. otitidiscaviarum, and tetA/B(58) across tetracycline-intermediate isolates. Additionally, resistance mechanisms beyond ARGs were observed, including species-specific presence of warA and aph(2''), and gyrA mutations largely correlating with ciprofloxacin resistance. Nonetheless, resistance in some strains lacking known resistance determinants indicates the presence of uncharacterized mechanisms.

Conclusions: These findings provide critical insights into the drug resistance patterns of Nocardia strains and antimicrobial resistance genes, highlighting the importance of ongoing genomic surveillance and personalized treatments.

诺卡菌临床分离株抗微生物药物耐药性的基因组和表型特征。
背景:诺卡菌对抗菌素的耐药性普遍存在,不同种类的耐药情况不同,这对有效的治疗策略提出了重大挑战。我们的研究旨在评估诺卡菌不同种类的抗菌药物敏感性,并探讨耐药表型与其潜在基因型之间的潜在相关性。方法:对中国13个省148株诺卡菌临床分离株进行分析。采用微肉汤稀释法测定15种抗菌药物的最低抑菌浓度(mic)。对所有分离株进行全基因组测序(WGS),然后在国家生物技术信息中心(NCBI)对70个人类来源的诺卡菌基因组进行生物信息学分析,包括物种验证、系统发育分析和抗微生物药物耐药性基因(ARGs)鉴定。结果:平均核苷酸鉴定(ANI)分析重新分类了几个错误鉴定的分离株,并发现了14个潜在的诺卡菌新种,强调了该属的分类复杂性。诺卡菌表现出不同的耐药特征:farcinica诺卡菌对头孢菌素和妥布霉素的耐药性升高;诺卡菌对β-内酰胺类和喹诺酮类药物广泛耐药;环叔诺卡菌对喹诺酮类药物、头孢吡肟和头孢西丁耐药。值得注意的是,所有物种的克拉霉素耐药性一直很高。此外,38.51%的诺卡菌分离株对两种或两种以上常用抗生素耐药,显示广泛存在多药耐药(MDR)。结果显示,耐磺胺甲恶唑/甲氧苄啶的N. farcinica中存在sul1,耐β-内酰胺的N. otitidiscaviarum中存在bla AST-1,四环素中间体分离株中存在tetA/B(58)。此外,除了ARGs之外,还观察到耐药机制,包括物种特异性的warA和aph(2”)的存在,以及gyrA突变与环丙沙星耐药性在很大程度上相关。尽管如此,一些缺乏已知抗性决定因素的菌株的抗性表明存在未表征的机制。结论:这些发现为诺卡菌菌株的耐药模式和抗微生物药物耐药基因提供了重要的见解,强调了持续的基因组监测和个性化治疗的重要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
7.90
自引率
7.00%
发文量
1817
审稿时长
14 weeks
期刊介绍: Frontiers in Cellular and Infection Microbiology is a leading specialty journal, publishing rigorously peer-reviewed research across all pathogenic microorganisms and their interaction with their hosts. Chief Editor Yousef Abu Kwaik, University of Louisville is supported by an outstanding Editorial Board of international experts. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide. Frontiers in Cellular and Infection Microbiology includes research on bacteria, fungi, parasites, viruses, endosymbionts, prions and all microbial pathogens as well as the microbiota and its effect on health and disease in various hosts. The research approaches include molecular microbiology, cellular microbiology, gene regulation, proteomics, signal transduction, pathogenic evolution, genomics, structural biology, and virulence factors as well as model hosts. Areas of research to counteract infectious agents by the host include the host innate and adaptive immune responses as well as metabolic restrictions to various pathogenic microorganisms, vaccine design and development against various pathogenic microorganisms, and the mechanisms of antibiotic resistance and its countermeasures.
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