Comparative genomics of the sequential Pseudomonas aeruginosa isolates obtained from the continuous imipenem stress evol
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GENOMICS, TRANSCRIPTOMICS, PROTEOMICS
Comparative genomics of the sequential Pseudomonas aeruginosa isolates obtained from the continuous imipenem stress evolution 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 Received: 24 July 2020 / Revised: 29 September 2020 / Accepted: 31 October 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
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. Keywords Pseudomonas aeruginosa . Imipenem . Resistance . Laboratory selection evolution . Comparative genomics
Introduction Supplementary Information The online version contains supplementary material available at https://doi.org/10.1007/s00253-02010994-1. * Xiurong Su [email protected] 1
State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Ningbo University, Ningbo, China
2
School of Marine Science, Ningbo University, 169 Qixing South Road, Beilun District, Ningbo, Zhejiang Province, China
3
National Marine Environmental Monitoring Center, Dalian, China
4
The First Institute of Oceanography, MNR, Qingdao, China
Pseudomonas aeruginosa is an environmental gram-negative γ-proteobacterium that shows wide adaption to distinct environments, such as soil, water, and numerous host organisms (Stover et al.
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