Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
Future Microbiol. 2012 Aug;7(8):959-78. doi: 10.2217/fmb.12.63.
A major contributor to the emergence of antibiotic resistance in Gram-positive bacterial pathogens is the expansion of acquired, inducible genetic elements. Although acquired, inducible antibiotic resistance is not new, the interest in its molecular basis has been accelerated by the widening distribution and often 'silent' spread of the elements responsible, the diagnostic challenges of such resistance and the mounting limitations of available agents to treat Gram-positive infections. Acquired, inducible antibiotic resistance elements belong to the accessory genome of a species and are horizontally acquired by transformation/recombination or through the transfer of mobile DNA elements. The two key, but mechanistically very different, induction mechanisms are: ribosome-sensed induction, characteristic of the macrolide-lincosamide-streptogramin B antibiotics and tetracycline resistance, leading to ribosomal modifications or efflux pump activation; and resistance by cell surface-associated sensing of β-lactams (e.g., oxacillin), glycopeptides (e.g., vancomycin) and the polypeptide bacitracin, leading to drug inactivation or resistance due to cell wall alterations.
导致革兰氏阳性细菌病原体抗生素耐药性出现的一个主要因素是可获得的、诱导性遗传元件的扩展。虽然可获得的、诱导性抗生素耐药性并不是新的，但由于负责这些耐药性的元件分布范围扩大且常常处于“潜伏”状态、这种耐药性的诊断挑战以及可用于治疗革兰氏阳性感染的现有药物的局限性不断增加，人们对其分子基础的兴趣有所增强。可获得的、诱导性抗生素耐药性元件属于物种的辅助基因组，通过转化/重组或通过移动 DNA 元件的转移而水平获得。两种关键但在机制上非常不同的诱导机制是：核糖体感应诱导，这是大环内酯类-林可酰胺类-链阳性菌素 B 抗生素和四环素耐药性的特征，导致核糖体修饰或外排泵激活；以及通过细胞表面对β-内酰胺类（如，苯唑西林）、糖肽类（如，万古霉素）和多肽杆菌肽的感应产生的耐药性，导致药物失活或由于细胞壁改变而产生耐药性。
