Comparative molecular profiling of multidrug-resistant Pseudomonas aeruginosa identifies novel mutations in regional clinical isolates from South India.
Comparative molecular profiling of multidrug-resistant Pseudomonas aeruginosa identifies novel mutations in regional clinical isolates from South India.
复制标题
DOI：
10.1093/jacamr/dlae001
复制
发表时间：
2024-02
影响因子：
3.4
通讯作者：
中科院分区：
文献类型：
--
作者：
我们试图分析耐多药临床铜绿假单胞菌分离株的抗生素敏感性和分子流行病学从印度南部使用非耐多药菌株作为参考。我们建立了一个全面的临床菌株库，包括2017年3月至2019年7月从南印度喀拉拉邦的患者中收集的58株分离株。对这些菌株进行抗生素敏感性试验、改良碳青霉烯灭活法测定碳青霉烯酶产量、PCR测序、比较序列分析以及与抗生素外排泵系统、氟喹诺酮耐药和碳青霉烯耐药相关的MDR决定簇的定量PCR。我们对MDR特异性SNP进行了计算机模拟。在我们收集的南印度铜绿假单胞菌临床分离株中，74.1%为MDR，55.8%对整个测试抗生素组耐药。所有MDR菌株均对左氧氟沙星耐药，93%对美罗培南耐药。我们在nalD中发现了七种不同的MDR特异性突变，其中三种是新的。mexA在对整个测试抗生素组具有抗性的菌株中显著过表达，而gyrA和gyrB在MDR分离株中过表达。氟喹诺酮类决定簇的突变与MDR表型显著相关，并观察到一种新的GyrA Y100 C取代。MDR分离株的碳青霉烯类耐药与我们样本中oprD的功能缺失突变和NDM（blaNDM-1）的高患病率相关。本研究提供了对铜绿假单胞菌临床分离株所采用的MDR机制的深入了解，这可能指导潜在的治疗方案的开发以改善临床结果。
We sought to analyse the antibiotic susceptibility profiles and molecular epidemiology of MDR clinical Pseudomonas aeruginosa isolates from South India using non-MDR isolates as a reference. We established a comprehensive clinical strain library consisting of 58 isolates collected from patients across the South Indian state of Kerala from March 2017 to July 2019. The strains were subject to antibiotic susceptibility testing, modified carbapenem inactivation method assay for carbapenemase production, PCR sequencing, comparative sequence analysis and quantitative PCR of MDR determinants associated with antibiotic efflux pump systems, fluoroquinolone resistance and carbapenem resistance. We performed in silico modelling of MDR-specific SNPs. Of our collection of South Indian P. aeruginosa clinical isolates, 74.1% were MDR and 55.8% were resistant to the entire panel of antibiotics tested. All MDR isolates were resistant to levofloxacin and 93% were resistant to meropenem. We identified seven distinct, MDR-specific mutations in nalD, three of which are novel. mexA was significantly overexpressed in strains that were resistant to the entire test antibiotic panel while gyrA and gyrB were overexpressed in MDR isolates. Mutations in fluoroquinolone determinants were significantly associated with MDR phenotype and a novel GyrA Y100C substitution was observed. Carbapenem resistance in MDR isolates was associated with loss-of-function mutations in oprD and high prevalence of NDM (blaNDM-1) within our sample. This study provides insight into MDR mechanisms adopted by P. aeruginosa clinical isolates, which may guide the potential development of therapeutic regimens to improve clinical outcomes.
登录
查看更多内容
影响因子：
3.9
作者：
Nguyen KV;Nguyen TV;Nguyen HTT;Le DV
通讯作者：
Le DV
影响因子：
5.2
作者：
Shu, Jwu-Ching;Kuo, An-Jing;Wu, Tsu-Lan
通讯作者：
Wu, Tsu-Lan
影响因子：
3.3
作者：
Murugan, Nandagopal;Malathi, Jambulingam;Madhavan, Hajib NarahariRao
通讯作者：
Madhavan, Hajib NarahariRao
影响因子：
1.9
作者：
Amudhan, M. Shanthi;Sekar, Uma;Balaraman, Sekar
通讯作者：
Balaraman, Sekar
DOI：
10.1016/s0140-6736(21)02724-0
发表时间：
2022-02-12
期刊：
Lancet (London, England)
影响因子：
--
作者：
Antimicrobial Resistance Collaborators
通讯作者：
Antimicrobial Resistance Collaborators