Tavares Letícia S, Silva Carolina S F, de Souza Vinicius C, da Silva Vânia L, Diniz Cláudio G, Santos Marcelo O
Department of Biology, University of Juiz de Fora Juiz de Fora, Brazil.
Department of Microbiology, Immunology and Infectious Diseases, University of Juiz de Fora Juiz de Fora, Brazil.
Front Microbiol. 2013 Dec 31;4:412. doi: 10.3389/fmicb.2013.00412.
The increasing number of antibiotic resistant bacteria motivates prospective research toward discovery of new antimicrobial active substances. There are, however, controversies concerning the cost-effectiveness of such research with regards to the description of new substances with novel cellular interactions, or description of new uses of existing substances to overcome resistance. Although examination of bacteria isolated from remote locations with limited exposure to humans has revealed an absence of antibiotic resistance genes, it is accepted that these genes were both abundant and diverse in ancient living organisms, as detected in DNA recovered from Pleistocene deposits (30,000 years ago). Indeed, even before the first clinical use of antibiotics more than 60 years ago, resistant organisms had been isolated. Bacteria can exhibit different strategies for resistance against antibiotics. New genetic information may lead to the modification of protein structure affecting the antibiotic carriage into the cell, enzymatic inactivation of drugs, or even modification of cellular structure interfering in the drug-bacteria interaction. There are still plenty of new genes out there in the environment that can be appropriated by putative pathogenic bacteria to resist antimicrobial agents. On the other hand, there are several natural compounds with antibiotic activity that may be used to oppose them. Antimicrobial peptides (AMPs) are molecules which are wide-spread in all forms of life, from multi-cellular organisms to bacterial cells used to interfere with microbial growth. Several AMPs have been shown to be effective against multi-drug resistant bacteria and have low propensity to resistance development, probably due to their unique mode of action, different from well-known antimicrobial drugs. These substances may interact in different ways with bacterial cell membrane, protein synthesis, protein modulation, and protein folding. The analysis of bacterial transcriptome may contribute to the understanding of microbial strategies under different environmental stresses and allows the understanding of their interaction with novel AMPs.
抗生素耐药菌数量的不断增加促使人们开展前瞻性研究，以发现新的抗菌活性物质。然而，对于此类研究的成本效益存在争议，涉及描述具有新型细胞相互作用的新物质，或描述现有物质的新用途以克服耐药性。尽管对来自人类接触有限的偏远地区分离出的细菌进行检测发现不存在抗生素耐药基因，但人们认为这些基因在古代生物中既丰富又多样，正如从更新世沉积物（3万年前）中回收的DNA所检测到的那样。事实上，甚至在60多年前抗生素首次临床使用之前，就已经分离出了耐药菌。细菌可以表现出不同的抗生素耐药策略。新的遗传信息可能导致蛋白质结构的改变，影响抗生素进入细胞、药物的酶促失活，甚至改变细胞结构以干扰药物与细菌的相互作用。环境中仍有大量新基因可供假定的病原菌利用来抵抗抗菌剂。另一方面，有几种具有抗生素活性的天然化合物可用于对抗它们。抗菌肽（AMPs）是广泛存在于所有生命形式中的分子，从多细胞生物到用于干扰微生物生长的细菌细胞。几种抗菌肽已被证明对多重耐药菌有效，且耐药性发展倾向较低，这可能是由于它们独特的作用方式，不同于知名的抗菌药物。这些物质可能以不同方式与细菌细胞膜、蛋白质合成、蛋白质调节和蛋白质折叠相互作用。细菌转录组分析可能有助于理解不同环境压力下的微生物策略，并有助于了解它们与新型抗菌肽的相互作用。
