Fitness Cost of Fluoroquinolone Resistance in Clinical Isolates of Pseudomonas aeruginosa Differs by Type III Secretion Genotype.
Fitness Cost of Fluoroquinolone Resistance in Clinical Isolates of Pseudomonas aeruginosa Differs by Type III Secretion Genotype.
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DOI：
10.3389/fmicb.2016.01591
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发表时间：
2016
影响因子：
5.2
通讯作者：
Wong-Beringer A
中科院分区：
文献类型：
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作者：
Agnello M;Finkel SE;Wong-Beringer A
氟喹诺酮（FQ）耐药性在铜绿假单胞菌的临床菌株中非常普遍，限制了治疗选择。我们之前报道过含有III型分泌系统exoU基因的高毒力菌株比含有exoS基因的菌株更有可能具有fq抗性，并且更有可能在gyrA/B和parC/E中获得抗性突变。我们假设，与exoS菌株相比，fq抗性对exoU菌株施加了更低的适应度成本，从而能够更好地适应fq丰富的临床环境。我们从三个exoU到三个exoS临床分离株中创建了parC中含有常见fq抗性点突变的等基因突变体，并使用头对头竞争法测试了体外适应度。该突变对exoU和exoS菌株的适应度有不同的影响。虽然添加parC突变显著提高了其中一个exo菌株的适应度，而其他两个不受影响，但所有三个exo菌株的适应度都普遍下降。此外，我们发现，与exoS菌株相比，exoU菌株可能能够通过更好地调节超卷曲来补偿与突变相关的适应度成本。这些结果可能为在fq耐药临床亚群中观察到的毒性外源ou基因型优势提供了生物学解释，并首次研究了与铜绿假单胞菌毒力基因型相关的fq耐药适应度成本的潜在差异。了解抗生素耐药性的适应度成本和补偿这些成本的可能性对于合理制定对抗抗生素耐药性问题的策略至关重要。
Fluoroquinolone (FQ) resistance is highly prevalent among clinical strains of Pseudomonas aeruginosa, limiting treatment options. We have reported previously that highly virulent strains containing the exoU gene of the type III secretion system are more likely to be FQ-resistant than strains containing the exoS gene, as well as more likely to acquire resistance-conferring mutations in gyrA/B and parC/E. We hypothesize that FQ-resistance imposes a lower fitness cost on exoU compared to exoS strains, thus allowing for better adaptation to the FQ-rich clinical environment. We created isogenic mutants containing a common FQ-resistance conferring point mutation in parC from three exoU to three exoS clinical isolates and tested fitness in vitro using head-to-head competition assays. The mutation differentially affected fitness in the exoU and exoS strains tested. While the addition of the parC mutation dramatically increased fitness in one of the exoU strains leaving the other two unaffected, all three exoS strains displayed a general decrease in fitness. In addition, we found that exoU strains may be able to compensate for the fitness costs associated with the mutation through better regulation of supercoiling compared to the exoS strains. These results may provide a biological explanation for the observed predominance of the virulent exoU genotype in FQ-resistant clinical subpopulations and represent the first investigation into potential differences in fitness costs of FQ-resistance that are linked to the virulence genotype of P. aeruginosa. Understanding the fitness costs of antibiotic resistance and possibilities of compensation for these costs is essential for the rational development of strategies to combat the problem of antibiotic resistance.