Fajardo Alicia, Martínez-Martín Nadia, Mercadillo María, Galán Juan C, Ghysels Bart, Matthijs Sandra, Cornelis Pierre, Wiehlmann Lutz, Tümmler Burkhard, Baquero Fernando, Martínez José L
Departamento de Biotecnología Microbiana, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CSIC), Cantoblanco, Madrid, Spain.
PLoS One. 2008 Feb 20;3(2):e1619. doi: 10.1371/journal.pone.0001619.
Bacteria with intrinsic resistance to antibiotics are a worrisome health problem. It is widely believed that intrinsic antibiotic resistance of bacterial pathogens is mainly the consequence of cellular impermeability and activity of efflux pumps. However, the analysis of transposon-tagged Pseudomonas aeruginosa mutants presented in this article shows that this phenotype emerges from the action of numerous proteins from all functional categories. Mutations in some genes make P. aeruginosa more susceptible to antibiotics and thereby represent new targets. Mutations in other genes make P. aeruginosa more resistant and therefore define novel mechanisms for mutation-driven acquisition of antibiotic resistance, opening a new research field based in the prediction of resistance before it emerges in clinical environments. Antibiotics are not just weapons against bacterial competitors, but also natural signalling molecules. Our results demonstrate that antibiotic resistance genes are not merely protective shields and offer a more comprehensive view of the role of antibiotic resistance genes in the clinic and in nature.
对抗生素具有内在抗性的细菌是一个令人担忧的健康问题。人们普遍认为，细菌病原体的内在抗生素抗性主要是细胞通透性和外排泵活性的结果。然而，本文中对转座子标签的铜绿假单胞菌突变体的分析表明，这种表型源于所有功能类别的众多蛋白质的作用。一些基因的突变使铜绿假单胞菌对抗生素更敏感，从而代表了新的靶点。其他基因的突变使铜绿假单胞菌更具抗性，因此定义了突变驱动获得抗生素抗性的新机制，开辟了一个基于在临床环境中抗性出现之前进行预测的新研究领域。抗生素不仅是对抗细菌竞争者的武器，也是天然信号分子。我们的结果表明，抗生素抗性基因不仅仅是保护屏障，并且为抗生素抗性基因在临床和自然界中的作用提供了更全面的观点。
