PLoS One：揭示绿脓杆菌致病性和耐药性之间的内在关联

近日，刊登在国际杂志<em>PLoS One</em>上的一篇研究报告中，来自南加州大学的研究者研究了绿脓杆菌III型分泌系统效应子蛋白的基因型与对氟喹诺酮类抗生素耐药机制之间的关系。研究成果或许为我们理解绿脓杆菌的致病性和耐药性提供新的思路。

绿脓杆菌，又名铜绿假单胞菌，是一种经常引发院内感染的革兰氏阴性机会致病菌。近年来，随着抗生素的滥用以及不合理使用，该菌对很多抗生素均产生了较强的耐药性，目前其对于氟喹诺酮类抗生素的耐药性逐渐增强。

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绿脓杆菌不光有极强的抗生素耐药性，其也可以分泌很多毒力因子来引发急慢性感染，尤其是III型分泌系统（T3SS）是铜绿假单胞菌主要的毒力系统，该系统常常引发细菌的急性感染。T3SS包括四种主要的效应毒力蛋白ExoS、ExoU、ExoT和ExoY。

在这项研究中，研究者Annie Wong-Beringer表示，他们在所收集到的270株分离菌株中，检测了T3SS效应子的基因型和对氟喹诺酮类抗生素耐药机制之间的关系。通过深入研究发现，相比含有高比例毒力因子ExoS的菌株（49%）来说，含有高比例ExoU的菌株（63%）对氟喹诺酮类抗生素耐药性更强。

通过对细菌T3SS的4个靶位基因<em>gyrA</em>，<em>gyrB</em>，<em>parC</em>，<em>parE</em>的氟喹诺酮类抗生素决定区域进行测序，研究者揭示了，相比高比例毒力因子ExoS的菌株来说，高比例ExoU的菌株突变是前者的2倍以上，而且其在靶位基因<em>gyrA</em>和<em>parC</em>的突变也是前者的2倍以上。

研究者的研究结果阐释了铜绿假单胞菌可以区别化地发展出与T3SS效应蛋白类型相应的耐药突变。毒性蛋白突变过程的不同揭示了耐药性的共进化和毒力特征或许更会在富含喹诺酮抗生素环境中表现出更强的毒力。
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<img src="http://www.bioon.com/biology/UploadFiles/201209/2012090322315147.jpg" alt="" width="113" height="149" border="0" />

<a title="" href="http://dx.doi.org/doi:10.1371/journal.pone.0042973" target="_blank">doi:10.1371/journal.pone.0042973</a>
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<br/><strong>Differentiation in Quinolone Resistance by Virulence Genotype in Pseudomonas aeruginosa</strong><br/>


Melissa Agnello, Annie Wong-Beringer*

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.

<br/>来源：生物谷

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