Differentiation in quinolone resistance by virulence genotype in Pseudomonas aeruginosa.
Differentiation in quinolone resistance by virulence genotype in Pseudomonas aeruginosa.
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DOI：
10.1371/journal.pone.0042973
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Wong-Beringer A
中科院分区：
文献类型：
--
作者：
Agnello M;Wong-Beringer A
铜绿假单胞菌是一种主要的病原体，由于广泛的处方，它对氟喹诺酮类抗生素的耐药性越来越强。感染氟喹诺酮耐药菌株的患者已出现不良后果。III型分泌系统（TTSS）是通过向宿主细胞注射效应毒素而引起急性感染的主要毒力决定因素。大多数菌株表现出独特的TTSS毒力基因型，由exoS或exoU基因的存在定义，分别编码两种效应毒素，exoS和exoU。特定的TTSS效应基因型先前已被证明对肺炎的毒力有不同的影响。在这项研究中，我们研究了270株呼吸道分离株的TTSS效应基因型与氟喹诺酮类药物耐药机制之间的关系。我们发现，尽管exoU+的总体患病率较低（38% exoU+ vs 56% exoS+），但exoU+菌株对氟喹诺酮类药物耐药的比例高于exoS+菌株（63% vs 49%, p = 0.03）。对4个靶基因（gyrA、gyrB、parC、parE）的喹诺酮耐药决定区（QRDRs）测序结果显示，在mic≤8µg/ml时，含有exoU基因的菌株比exoS+菌株更容易发生≥2个突变（13%比无突变），gyrA和parC同时发生突变的可能性是exoS+菌株的两倍（48%比24% p = 0.0439）。我们的研究结果表明，铜绿假单胞菌菌株产生的耐药突变与TTSS效应基因型和毒性更强的exoU+亚群有关。观察到的毒力基因型突变过程的差异表明，在富含喹诺酮的临床环境中，耐药性和毒力性状的共同进化倾向于更强毒力的基因型。
Pseudomonas aeruginosa is a leading pathogen that has become increasingly resistant to the fluoroquinolone antibiotics due to widespread prescribing. Adverse outcomes have been shown for patients infected with fluoroquinolone-resistant strains. The type III secretion system (TTSS) is a major virulence determinant during acute infections through the injection of effector toxins into host cells. Most strains exhibit a unique TTSS virulence genotype defined by the presence of either exoS or exoU gene encoding two of the effector toxins, ExoS and ExoU, respectively. Specific TTSS effector genotype has been shown previously to differentially impact virulence in pneumonia. In this study, we examined the relationship between TTSS effector genotype and fluoroquinolone resistance mechanisms in a collection of 270 respiratory isolates. We found that a higher proportion of exoU+ strains were fluoroquinolone-resistant compared to exoS+ strains (63% vs 49%, p = 0.03) despite its lower overall prevalence (38% exoU+ vs 56% exoS+). Results from sequencing the quinolone resistance determining regions (QRDRs) of the 4 target genes (gyrA, gyrB, parC, parE) indicated that strains containing the exoU gene were more likely to acquire ≥2 mutations than exoS+ strains at MICs ≤8 µg/ml (13% vs none) and twice as likely to have mutations in both gyrA and parC than exoS+ strains (48% vs 24% p = 0.0439). Our findings indicate that P. aeruginosa strains differentially develop resistance-conferring mutations that correlate with TTSS effector genotype and the more virulent exoU+ subpopulation. Differences in mutational processes by virulence genotype that were observed suggest co-evolution of resistance and virulence traits favoring a more virulent genotype in the quinolone-rich clinical environment.