Culyba Matthew J, Mo Charlie Y, Kohli Rahul M
Biochemistry. 2015 Jun 16;54(23):3573-82. doi: 10.1021/acs.biochem.5b00109. Epub 2015 Jun 5.
Bacteria possess a remarkable ability to rapidly adapt and evolve in response to antibiotics. Acquired antibiotic resistance can arise by multiple mechanisms but commonly involves altering the target site of the drug, enzymatically inactivating the drug, or preventing the drug from accessing its target. These mechanisms involve new genetic changes in the pathogen leading to heritable resistance. This recognition underscores the importance of understanding how such genetic changes can arise. Here, we review recent advances in our understanding of the processes that contribute to the evolution of antibiotic resistance, with a particular focus on hypermutation mediated by the SOS pathway and horizontal gene transfer. We explore the molecular mechanisms involved in acquired resistance and discuss their viability as potential targets. We propose that additional studies into these adaptive mechanisms not only can provide insights into evolution but also can offer a strategy for potentiating our current antibiotic arsenal.
细菌具有非凡的能力，能够迅速适应抗生素并随之进化。获得性抗生素耐药性可通过多种机制产生，但通常涉及改变药物的靶点、酶促使药物失活或阻止药物到达其靶点。这些机制涉及病原体中的新基因变化，从而导致可遗传的耐药性。这一认识凸显了了解此类基因变化如何产生的重要性。在此，我们综述了我们对促成抗生素耐药性进化过程的理解方面的最新进展，特别关注由SOS途径介导的超突变和水平基因转移。我们探讨了获得性耐药所涉及的分子机制，并讨论了它们作为潜在靶点的可行性。我们提出，对这些适应性机制的进一步研究不仅可以为进化提供见解，还可以提供一种增强我们当前抗生素库的策略。
