Shahzad Shakeel, Willcox Mark D P, Rayamajhee Binod
School of Optometry and Vision Science, University of New South Wales, Sydney, NSW 2052, Australia.
Antibiotics (Basel). 2023 Nov 6;12(11):1597. doi: 10.3390/antibiotics12111597.
The global rise in antibiotic resistance in bacteria poses a major challenge in treating infectious diseases. Polymyxins (e.g., polymyxin B and colistin) are last-resort antibiotics against resistant Gram-negative bacteria, but the effectiveness of polymyxins is decreasing due to widespread resistance among clinical isolates. The aim of this literature review was to decipher the evolving mechanisms of resistance to polymyxins among pathogens of clinical significance. We deciphered the molecular determinants of polymyxin resistance, including distinct intrinsic molecular pathways of resistance as well as evolutionary characteristics of mobile colistin resistance. Among clinical isolates, stains represent a diversified evolution of resistance, with distinct molecular mechanisms of intrinsic resistance including D, ACD, and R gene deletion. On the other hand, , , and are usually resistant via the PhoP-PhoQ and PmrA-PmrB pathways. Molecular evolutionary analysis of genes was undertaken to show relative relatedness across the ten main lineages. Understanding the molecular determinants of resistance to polymyxins may help develop suitable and effective methods for detecting polymyxin resistance determinants and the development of novel antimicrobial molecules.
全球细菌抗生素耐药性的上升对传染病治疗构成了重大挑战。多粘菌素（如多粘菌素B和黏菌素）是对抗耐药革兰氏阴性菌的最后一道防线抗生素，但由于临床分离株中广泛存在耐药性，多粘菌素的有效性正在下降。这篇文献综述的目的是解读具有临床意义的病原体对多粘菌素耐药性的演变机制。我们解读了多粘菌素耐药性的分子决定因素，包括不同的内在分子耐药途径以及可移动黏菌素耐药性的进化特征。在临床分离株中，菌株呈现出多样化的耐药进化，具有不同的内在耐药分子机制，包括D、ACD和R基因缺失。另一方面，、和通常通过PhoP-PhoQ和PmrA-PmrB途径产生耐药性。对基因进行了分子进化分析，以显示十个主要谱系之间的相对相关性。了解多粘菌素耐药性的分子决定因素可能有助于开发合适有效的方法来检测多粘菌素耐药性决定因素，并开发新型抗菌分子。
