Department of Microbial Sciences, University of Surrey, Guildford, UK.
School of Civil, Mining and Environmental Engineering, University of Wollongong, Wollongong, Australia.
Microbiology (Reading). 2023 Nov;169(11). doi: 10.1099/mic.0.001403.
Antibiotic persistence is a phenomenon observed when genetically susceptible cells survive long-term exposure to antibiotics. These 'persisters' are an intrinsic component of bacterial populations and stem from phenotypic heterogeneity. Persistence to antibiotics is a concern for public health globally, as it increases treatment duration and can contribute to treatment failure. Furthermore, there is a growing array of evidence that persistence is a 'stepping-stone' for the development of genetic antimicrobial resistance. Urinary tract infections (UTIs) are a major contributor to antibiotic consumption worldwide, and are known to be both persistent (i.e. affecting the host for a prolonged period) and recurring. Currently, in clinical settings, routine laboratory screening of pathogenic isolates does not determine the presence or the frequency of persister cells. Furthermore, the majority of research undertaken on antibiotic persistence has been done on lab-adapted bacterial strains. In the study presented here, we characterized antibiotic persisters in a panel of clinical uropathogenic isolates collected from hospitals in the UK and Australia. We found that a urine-pH mimicking environment not only induces higher levels of antibiotic persistence to meropenem and colistin than standard laboratory growth conditions, but also results in rapid development of transient colistin resistance, regardless of the genetic resistance profile of the isolate. Furthermore, we provide evidence for the presence of multiple virulence factors involved in stress resistance and biofilm formation in the genomes of these isolates, whose activities have been previously shown to contribute to the formation of persister cells.
抗生素持久性是指在长期接触抗生素的情况下，遗传上易感的细胞仍然存活的现象。这些“持久菌”是细菌种群的固有组成部分，源于表型异质性。抗生素持久性对全球公共卫生构成了威胁，因为它会延长治疗时间，并可能导致治疗失败。此外，越来越多的证据表明，持久性是遗传抗菌耐药性发展的“垫脚石”。尿路感染（UTI）是全球抗生素消耗的主要原因，并且已知其具有持久性（即对宿主的影响持续很长时间）和复发性。目前，在临床环境中，对病原体分离物的常规实验室筛查并不能确定持久菌细胞的存在或频率。此外，大多数关于抗生素持久性的研究都是在实验室适应的细菌菌株上进行的。在本研究中，我们对从英国和澳大利亚医院收集的一组临床尿路致病性分离株中的抗生素持久菌进行了表征。我们发现，尿液 pH 模拟环境不仅会导致对美罗培南和多粘菌素的抗生素持久性水平高于标准实验室生长条件，而且无论分离株的遗传耐药性如何，都会导致短暂的多粘菌素耐药性迅速发展。此外，我们还提供了证据，证明这些分离株的基因组中存在多种与应激抗性和生物膜形成有关的毒力因子，其活性先前已被证明有助于持久菌细胞的形成。
