Comparative genomics of the sequential Pseudomonas aeruginosa isolates obtained from the continuous imipenem stress evolution,Applied Microbiology and Biotechnology

当前位置： X-MOL 学术 › Appl. Microbiol. Biotechnol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Comparative genomics of the sequential Pseudomonas aeruginosa isolates obtained from the continuous imipenem stress evolution
Applied Microbiology and Biotechnology ( IF 5 ) Pub Date : 2020-11-05 , DOI: 10.1007/s00253-020-10994-1
Chenyang Lu _{1,

2} , Jun Zhou _{1,

2} , Tao Zhang _{1,

2} , Chenghua Li _{1,

2} , Jiong Chen _{1,

2} , Jingfeng Fan ₃ , Lingyun Qu ₄ , Xiurong Su _{1,

2}

Affiliation

Abstract

Pseudomonas aeruginosa is a major opportunistic human pathogen that causes nosocomial infections, and the proportion of carbapenem resistance has recently dramatically increased in P. aeruginosa due to the overuse of them. In this study, strains G10 and G20, with minimum inhibitory concentration (MIC) of imipenem of 16 μg/ml and more than 32 μg/ml, were isolated during continuous subculture of cells exposed to stepwise increasing concentrations of imipenem, respectively. The genomes of G10 and G20 were sequenced and compared with parental strain (P. aeruginosa ATCC 27853, G0). There were 59, 59, and 58 genes involved in antibiotic resistance which were predicted in G0, G10, and G20, respectively, while 374, 366, and 363 genes involved in virulence factors were identified among these three strains. Due to the significantly different MICs of imipenem and highly similar profiles of antibiotic resistance and virulence factors related genes among three strains, the specific genetic variations that occurred were identified and compared, including single nucleotide polymorphisms (SNPs), insertions and deletions (InDels), and structural variations (SVs). The increase in the MIC of imipenem was proposed to be linked to mutations involved in polyamine biosynthesis, biofilm formation, OprD, and efflux pump functions. This study aims to clarify the underlying mechanism of imipenem resistance and provide alternative strategies for reducing resistance in P. aeruginosa.

Key points

• Strains with different imipenem MIC were obtained via laboratory selection evolution.

• Whole genomes of two strains with different MIC of imipenem were sequenced.

• Underlying mechanism of imipenem resistance was clarified via comparative genomics.

中文翻译：

从连续亚胺培南应激进化中获得的连续铜绿假单胞菌分离物的比较基因组学

摘要

铜绿假单胞菌是导致医院感染的主要机会性人类病原体，并且由于过度使用它们，最近在铜绿假单胞菌中碳青霉烯类耐药的比例急剧增加。在这项研究中，菌株 G10 和 G20 的亚胺培南最小抑制浓度 (MIC) 分别为 16 μg/ml 和超过 32 μg/ml，分别在暴露于逐步增加浓度的亚胺培南的细胞的连续传代培养过程中分离出来。对 G10 和 G20 的基因组进行测序并与亲本菌株 ( P. aeruginosaATCC 27853，G0）。在G0、G10和G20中分别预测出59、59和58个涉及抗生素耐药性的基因，而在这三个菌株中鉴定出374、366和363个涉及毒力因子的基因。由于亚胺培南的 MIC 显着不同，并且三个菌株之间抗生素耐药性和毒力因子相关基因的谱高度相似，因此鉴定和比较了发生的特定遗传变异，包括单核苷酸多态性 (SNP)、插入和缺失 (InDels)、和结构变异（SV）。亚胺培南 MIC 的增加被认为与多胺生物合成、生物膜形成、OprD 和外排泵功能所涉及的突变有关。铜绿假单胞菌。