Alonso Ana, Morales Gracia, Escalante Ricardo, Campanario Ester, Sastre Leandro, Martinez Jose L
Departamento de Biotecnología Microbiana, Centro Nacional de Biotecnología, CSIC, Campus Universidad Autónoma de Madrid, Cantoblanco, 28049-Madrid.
J Antimicrob Chemother. 2004 Mar;53(3):432-4. doi: 10.1093/jac/dkh074. Epub 2004 Jan 22.
The use of antibiotics for the treatment of infectious diseases has led to important changes in the structure of pathogenic bacterial populations. However, these changes could be buffered if the expression of antibiotic resistance genes were to lead to the counter-selection of antibiotic-resistant strains in antibiotic-free environments. To test the effect of antibiotic resistance on bacterial fitness, we analysed the effect of the overproduction of the multidrug efflux pump SmeDEF on the physiology of Stenotrophomonas maltophilia. SmeDEF confers resistance to antibiotics belonging to different structural families, and its overexpression is associated with an antibiotic resistance phenotype in clinical isolates of S. maltophilia.
Two S. maltophilia isogenic strains were analysed: the wild-type strain D457 and strain D457R, which is a SmeDEF overproducer. In co-culture experiments, under non-selective pressure the wild-type strain displaced the mutant strain D457R. Metabolic profiling showed that SmeDEF overproduction leads to several changes in S. maltophilia metabolism. Using a Dictyostelium discoideum model of bacterial virulence, we found overexpression of SmeDEF to be associated with a reduction in S. maltophilia virulence.
Together, these data indicate that overexpression of the multidrug efflux pump SmeDEF causes a metabolic burden for S. maltophilia.
使用抗生素治疗传染病已导致致病细菌种群结构发生重大变化。然而，如果抗生素抗性基因的表达导致在无抗生素环境中对抗生素抗性菌株进行反向选择，这些变化可能会得到缓冲。为了测试抗生素抗性对细菌适应性的影响，我们分析了多药外排泵SmeDEF过量表达对嗜麦芽窄食单胞菌生理学的影响。SmeDEF赋予对不同结构家族抗生素的抗性，其过表达与嗜麦芽窄食单胞菌临床分离株中的抗生素抗性表型相关。
分析了两株嗜麦芽窄食单胞菌同基因菌株：野生型菌株D457和菌株D457R，后者是SmeDEF过量生产者。在共培养实验中，在非选择性压力下，野生型菌株取代了突变菌株D457R。代谢谱分析表明，SmeDEF过量表达导致嗜麦芽窄食单胞菌代谢发生若干变化。使用盘基网柄菌细菌毒力模型，我们发现SmeDEF过表达与嗜麦芽窄食单胞菌毒力降低有关。
这些数据共同表明，多药外排泵SmeDEF的过表达给嗜麦芽窄食单胞菌带来了代谢负担。
