2012年9月3日 訊 /生物谷BIOON/ --近日,，刊登在國際雜志PLoS One上的一篇研究報告中,，來自南加州大學(xué)的研究者研究了綠膿桿菌III型分泌系統(tǒng)效應(yīng)子蛋白的基因型與對氟喹諾酮類抗生素耐藥機制之間的關(guān)系。研究成果或許為我們理解綠膿桿菌的致病性和耐藥性提供新的思路,。
綠膿桿菌,，又名銅綠假單胞菌，是一種經(jīng)常引發(fā)院內(nèi)感染的革蘭氏陰性機會致病菌,。近年來,，隨著抗生素的濫用以及不合理使用，該菌對很多抗生素均產(chǎn)生了較強的耐藥性，目前其對于氟喹諾酮類抗生素的耐藥性逐漸增強,。
綠膿桿菌不光有極強的抗生素耐藥性,，其也可以分泌很多毒力因子來引發(fā)急慢性感染，尤其是III型分泌系統(tǒng)（T3SS）是銅綠假單胞菌主要的毒力系統(tǒng),，該系統(tǒng)常常引發(fā)細菌的急性感染,。T3SS包括四種主要的效應(yīng)毒力蛋白ExoS、ExoU,、ExoT和ExoY,。
在這項研究中，研究者Annie Wong-Beringer表示,，他們在所收集到的270株分離菌株中,，檢測了T3SS效應(yīng)子的基因型和對氟喹諾酮類抗生素耐藥機制之間的關(guān)系。通過深入研究發(fā)現(xiàn),，相比含有高比例毒力因子ExoS的菌株（49%）來說,，含有高比例ExoU的菌株（63%）對氟喹諾酮類抗生素耐藥性更強。
通過對細菌T3SS的4個靶位基因gyrA,，gyrB,，parC，parE的氟喹諾酮類抗生素決定區(qū)域進行測序,，研究者揭示了,，相比高比例毒力因子ExoS的菌株來說，高比例ExoU的菌株突變是前者的2倍以上,，而且其在靶位基因gyrA和parC的突變也是前者的2倍以上,。
研究者的研究結(jié)果闡釋了銅綠假單胞菌可以區(qū)別化地發(fā)展出與T3SS效應(yīng)蛋白類型相應(yīng)的耐藥突變。毒性蛋白突變過程的不同揭示了耐藥性的共進化和毒力特征或許更會在富含喹諾酮抗生素環(huán)境中表現(xiàn)出更強的毒力,。（生物谷Bioon.com）
doi:10.1371/journal.pone.0042973
PMC:
PMID:
Differentiation in Quinolone Resistance by Virulence Genotype in Pseudomonas aeruginosa
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.
