Centro de Análises Proteômicas e Bioquímicas, Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, Brasilia, Brazil.
FASEB J. 2013 Apr;27(4):1291-303. doi: 10.1096/fj.12-221127. Epub 2013 Jan 24.
Antibiotics are important therapeutic agents commonly used for the control of bacterial infectious diseases; however, resistance to antibiotics has become a global public health problem. Therefore, effective therapy in the treatment of resistant bacteria is necessary and, to achieve this, a detailed understanding of mechanisms that underlie drug resistance must be sought. To fill the multiple gaps that remain in understanding bacterial resistance, proteomic tools have been used to study bacterial physiology in response to antibiotic stress. In general, the global analysis of changes in the protein composition of bacterial cells in response to treatment with antibiotic agents has made it possible to construct a database of proteins involved in the process of resistance to drugs with similar mechanisms of action. In the past few years, progress in using proteomic tools has provided the most realistic picture of the infective process, since these tools detect the end products of gene biosynthetic pathways, which may eventually determine a biological phenotype. In most bacterial species, alterations occur in energy and nitrogen metabolism regulation; glucan biosynthesis is up-regulated; amino acid, protein, and nucleotide synthesis is affected; and various proteins show a stress response after exposing these microorganisms to antibiotics. These issues have been useful in identifying targets for the development of novel antibiotics and also in understanding, at the molecular level, how bacteria resist antibiotics.
抗生素是常用于控制细菌感染性疾病的重要治疗药物；然而，抗生素耐药性已成为全球公共卫生问题。因此，有必要寻求有效的治疗耐药菌的方法，而要实现这一目标，必须深入了解耐药性的潜在机制。为了填补在理解细菌耐药性方面仍然存在的多个空白，蛋白质组学工具已被用于研究细菌对抗生素应激的生理反应。一般来说，对细菌细胞在抗生素治疗下的蛋白质组成变化进行全面分析，使得构建一个数据库成为可能，其中包含了具有相似作用机制的药物耐药性过程中涉及的蛋白质。在过去的几年中，蛋白质组学工具的应用进展为感染过程提供了最真实的图景，因为这些工具检测基因生物合成途径的最终产物，这些产物最终可能决定生物学表型。在大多数细菌物种中，能量和氮代谢调节发生改变；葡聚糖生物合成上调；氨基酸、蛋白质和核苷酸合成受到影响；并且在将这些微生物暴露于抗生素后，各种蛋白质会产生应激反应。这些问题有助于确定开发新型抗生素的靶点，并在分子水平上了解细菌如何对抗生素产生耐药性。
