Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
Nat Rev Microbiol. 2019 Aug;17(8):479-496. doi: 10.1038/s41579-019-0218-1. Epub 2019 Jun 24.
Antibiotic heteroresistance is a phenotype in which a bacterial isolate contains subpopulations of cells that show a substantial reduction in antibiotic susceptibility compared with the main population. Recent work indicates that heteroresistance is very common for several different bacterial species and antibiotic classes. The resistance phenotype is often unstable, and in the absence of antibiotic pressure it rapidly reverts to susceptibility. A common mechanistic explanation for the instability is the occurrence of genetically unstable tandem amplifications of genes that cause resistance. Due to their instability, low frequency and transient character, it is challenging to detect and study these subpopulations, which often leads to difficulties in unambiguously classifying bacteria as susceptible or resistant. Finally, in vitro experiments, mathematical modelling, animal infection models and clinical studies show that the resistant subpopulations can be enriched during antibiotic exposure, and increasing evidence suggests that heteroresistance can lead to treatment failure.
抗生素异质性耐药是一种表型，其中细菌分离株包含亚群细胞，与主要群体相比，这些亚群细胞对抗生素的敏感性显著降低。最近的研究表明，异质性耐药在几种不同的细菌物种和抗生素类别中非常常见。耐药表型通常不稳定，在没有抗生素压力的情况下，它会迅速恢复为敏感性。导致耐药性的基因串联扩增的遗传不稳定性是这种不稳定性的常见机制解释。由于其不稳定性、低频率和瞬时特性，检测和研究这些亚群具有挑战性，这往往导致难以明确将细菌分类为敏感或耐药。最后，体外实验、数学建模、动物感染模型和临床研究表明，在抗生素暴露期间，耐药亚群可以被富集，越来越多的证据表明异质性耐药可导致治疗失败。
