Fitness cost of fluoroquinolone resistance in Salmonella enterica serovar Typhimurium
Fitness cost of fluoroquinolone resistance in Salmonella enterica serovar Typhimurium
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DOI：
10.1099/jmm.0.05178-0
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发表时间：
2003-08-01
影响因子：
3
通讯作者：
Chaslus-Dancla, E
中科院分区：
文献类型：
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作者：
Giraud, E;Cloeckaert, A;Chaslus-Dancla, E
与其他致病性肠杆菌相比，沙门氏菌对氟喹诺酮（FQ）的高水平耐药性仍然很少见。在这项工作中提供的数据支持的假设，赋予高水平的FQ抗性鲑鱼的机制有一个令人望而却步的健身成本，因此可能会限制高抗性克隆的出现。在体外对环丙沙星高度耐药的突变体（MIC = 8和16 μ g/ml）显示世代时间为1（.）4-并且比它们的亲本菌株长2倍，并且不能定殖于鸡的肠道。电子显微镜显示这些突变体之一生长到稳定期的形态改变。在体内筛选出的对环丙沙星具有中等抗性（MIC = 2 μ g/ml）的突变体在固体培养基上也表现出生长缺陷，但在液体培养中具有正常的世代时间，并定殖在鸡的肠道中。在没有抗生素选择压力的体外或体内传代后，观察到适应性成本的部分逆转，这与喹诺酮类和其他无关抗生素的耐药性略有下降有关，但与gyrA突变的丢失无关。
High-level fluoroquinolone (FQ) resistance is still infrequent in salmonellae, compared with other pathogenic enterobacteria. Data provided in this work support the hypothesis that the mechanisms that confer high-level FQ resistance on salmonellae have a prohibitive fitness cost and may thus limit the emergence of highly resistant clones. In vitro mutants that were highly resistant to ciprofloxacin (MIC = 8 and 16 mug ml(-1)) showed generation times 1(.)4- and 2-fold longer than their parent strains and were unable to colonize the gut of chickens. Electron microscopy showed an altered morphology for one of these mutants grown to stationary phase. Mutants selected in vivo and exhibiting intermediate resistance to ciprofloxacin (MIC = 2 mug ml(-1)) also showed growth defects on solid media but had normal generation times in liquid culture and colonized the gut of chickens. After in vitro or in vivo passage in the absence of antibiotic selective pressure, partial reversals of the fitness cost were observed, which were associated with slight decreases in resistance to quinolones and other unrelated antibiotics, but were not linked to the loss of gyrA mutations.