Departamento de Biotecnología Microbiana, Centro Nacional de Biotecnología, CNB-CSIC, Darwin 3, Cantoblanco, 28049, Madrid, Spain.
Future Med Chem. 2012 Mar;4(3):347-59. doi: 10.4155/fmc.12.2.
Despite the relevance of infectious disease as main causes of human morbidity and mortality, the development of new antibacterials is not among the highest priorities for pharmaceutical companies. Regulatory and economic issues, together with the lack of novel targets, might justify the reduced rate of discovery of new antimicrobials. With the increasing number of antibiotic resistant pathogens, the mechanisms of resistance appear as appealing alternatives for developing new drugs. Defining the elements that contribute to the characteristic phenotype of susceptibility to antibiotics of a given bacterial species, will serve to find those targets. Recent information on the elements forming part of bacterial intrinsic resistomes and on the inhibitors of resistance currently under development are presented. The possibility of developing new therapeutic procedures based on the administration, together with antibiotics of specific metabolic intermediates capable of increasing the susceptibility to antibiotics by altering bacterial physiology, are also discussed.
尽管传染病是导致人类发病率和死亡率的主要原因之一，但制药公司并没有将开发新的抗菌药物作为最高优先事项之一。监管和经济问题，以及缺乏新的靶标，可能解释了新抗菌药物发现率的降低。随着抗生素耐药病原体数量的增加，耐药机制似乎成为开发新药的有吸引力的替代方法。确定导致特定细菌物种对抗生素敏感性特征表型的因素，将有助于找到这些靶标。本文介绍了构成细菌固有耐药组的部分元素，以及目前正在开发的耐药抑制剂。还讨论了基于给药的新治疗方法的可能性，以及与特定代谢中间产物一起给药的可能性，这些中间产物能够通过改变细菌生理学来增加对抗生素的敏感性。
