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铜绿假单胞菌对四种不同抗生素抗性突变体的比较转录分析。

Comparative transcription analysis of resistant mutants against four different antibiotics in Pseudomonas aeruginosa.

机构信息

School of Basic Medical Sciences, Henan University of Science and Technology, Luoyang, 471003, China.

School of Basic Medical Sciences, Henan University of Science and Technology, Luoyang, 471003, China.

出版信息

Microb Pathog. 2021 Nov;160:105166. doi: 10.1016/j.micpath.2021.105166. Epub 2021 Sep 1.

Abstract

The emergence of antibiotic resistance has severely impaired the treatment of infections caused by Pseudomonas aeruginosa. There are few studies related to comparing the antibiotics resistance mechanisms of P. aeruginosa against different antibiotics. In this study, RNA sequencing was used to investigate the differences of transcriptome between wild strain and four antibiotics resistant strains of P. aeruginosa PAO1 (polymyxin B, ciprofloxacin, doxycycline, and ceftriaxone). Compared to the wild strain, 1907, 495, 2402, and 116 differentially expressed genes (DEGs) were identified in polymyxin B, ciprofloxacin, doxycycline, and ceftriaxone resistant PAO1, respectively. After analysis of genes related to antimicrobial resistance, we found genes implicated in biofilm formation (pelB, pelC, pelD, pelE, pelF, pelG, algA, algF, and alg44) were significantly upregulated in polymyxin B-resistant PAO1, efflux pump genes (mexA, mexB, oprM) and biofilm formation genes (pslJ, pslK and pslN) were upregulated in ciprofloxacin-resistant PAO1; other efflux pump genes (mexC, mexD, oprJ) were upregulated in doxycycline-resistant PAO1; ampC were upregulated in ceftriaxone-resistant PAO1. As a consequence of antibiotic resistance, genes related to virulence factors such as type Ⅱ secretion system (lasA, lasB and piv) were significantly upregulated in polymyxin B-resistant PAO1, and type Ⅲ secretion system (exoS, exoT, exoY, exsA, exsB, exsC, exsD, pcrV, popB, popD, pscC, pscE, pscG, and pscJ) were upregulated in doxycycline-resistant PAO1. While, ampC were upregulated in ceftriaxone-resistant PAO1. In addition, variants were obtained in wild type and four antibiotics resistant PAO1. Our findings provide a comparative transcriptome analysis of antibiotic resistant mutants selected by different antibiotics, and might assist in identifying potential therapeutic strategies for P. aeruginosa infection.

摘要

抗生素耐药性的出现严重影响了铜绿假单胞菌感染的治疗。目前关于铜绿假单胞菌对不同抗生素耐药机制的研究较少。本研究采用 RNA 测序技术,比较了野生型铜绿假单胞菌 PAO1 及其对多粘菌素 B、环丙沙星、强力霉素和头孢曲松耐药的 4 个突变株的转录组差异。与野生型相比,多粘菌素 B、环丙沙星、强力霉素和头孢曲松耐药的 PAO1 分别有 1907、495、2402 和 116 个差异表达基因(DEGs)。对与抗菌药物耐药相关的基因分析后发现,在多粘菌素 B 耐药的 PAO1 中,与生物膜形成相关的基因(pelB、pelC、pelD、pelE、pelF、pelG、algA、algF 和 alg44)显著上调,在环丙沙星耐药的 PAO1 中,外排泵基因(mexA、mexB、oprM)和生物膜形成基因(pslJ、pslK 和 pslN)上调;在强力霉素耐药的 PAO1 中,其他外排泵基因(mexC、mexD、oprJ)上调;在头孢曲松耐药的 PAO1 中,ampC 上调。由于抗生素耐药,在多粘菌素 B 耐药的 PAO1 中,与毒力因子相关的基因,如 II 型分泌系统(lasA、lasB 和 piv)显著上调,在强力霉素耐药的 PAO1 中,III 型分泌系统(exoS、exoT、exoY、exsA、exsB、exsC、exsD、pcrV、popB、popD、pscC、pscE、pscG 和 pscJ)上调;而在头孢曲松耐药的 PAO1 中,ampC 上调。此外,在野生型和 4 个抗生素耐药的 PAO1 中均获得了变异。本研究提供了不同抗生素选择的耐药突变体的比较转录组分析,可能有助于确定铜绿假单胞菌感染的潜在治疗策略。

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