Mousavi Seyyed Mohammad Javad, Hosseinpour Minoo, Kodori Mansoor, Rafiei Fariba, Mahmoudi Mohammad, Shahraki Hojat, Shiri Hamidreza, Hashemi Ali, Sharahi Javad Yasbolaghi
Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
Department of Microbiology, Virology and Microbial Toxins, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran.
Microb Pathog. 2025 Apr;201:107317. doi: 10.1016/j.micpath.2025.107317. Epub 2025 Jan 23.
Following a period of disuse owing to the emergence of multidrug-resistant Gram-negative bacteria, colistin has regained global attention as an antibiotic of last resort. The resurgence in its utilization has led to a concurrent increase in acquired resistance, presenting a significant challenge in clinical treatment. Predominantly, resistance mechanisms involve alterations in the lipid A component of the lipopolysaccharide (LPS) structure. These alterations are facilitated by the addition of cationic phosphoethanolamine (pEtN) or 4-amino-L-arabinose, often driven by the upregulation of two-component regulatory systems such as PmrAB and PhoPQ. Structural components of bacteria, such as capsules and efflux pumps, can also play an important role in the resistance mechanism. In addition to these biochemical modifications, structural components of bacteria like capsules and efflux pumps also play crucial roles in mediating resistance. Another significant mechanism is the acquisition of the plasmid-mediated mobilized colistin resistance (mcr) gene, which poses a global health threat due to its ability to transfer between different bacterial genera. Contemporary strategies to combat colistin resistance include the development and use of novel drugs and inhibitors. To devise effective interventions, it is imperative to first elucidate the precise mechanisms of colistin resistance and determine the roles of various contributing factors.
由于多重耐药革兰氏阴性菌的出现，多粘菌素曾一度停用，如今作为一种最后手段的抗生素再次受到全球关注。其使用的复苏导致获得性耐药同时增加，给临床治疗带来了重大挑战。主要地，耐药机制涉及脂多糖（LPS）结构中脂质A成分的改变。这些改变通过添加阳离子磷酸乙醇胺（pEtN）或4-氨基-L-阿拉伯糖而促进，这通常由双组分调节系统如PmrAB和PhoPQ的上调驱动。细菌的结构成分，如荚膜和外排泵，在耐药机制中也可发挥重要作用。除了这些生化修饰外，细菌的结构成分如荚膜和外排泵在介导耐药方面也起着关键作用。另一个重要机制是获得质粒介导的可移动多粘菌素耐药（mcr）基因，由于其能够在不同细菌属之间转移，对全球健康构成威胁。对抗多粘菌素耐药的当代策略包括开发和使用新型药物及抑制剂。为了设计有效的干预措施，首先必须阐明多粘菌素耐药的确切机制，并确定各种促成因素的作用。
