Department of Chemical and Biomolecular Engineering, University of Houston, Houston, Texas, USA.
Department of Chemical and Biomolecular Engineering, University of Houston, Houston, Texas, USA
Antimicrob Agents Chemother. 2020 Apr 21;64(5). doi: 10.1128/AAC.02393-19.
Bacterial persisters are phenotypic variants that temporarily demonstrate an extraordinary tolerance toward antibiotics. Persisters have been linked to the recalcitrance of biofilm-related infections; hence, a complete understanding of their physiology can lead to improvement of therapeutic strategies for such infections. Mechanisms pertaining to persister formation are thought to be associated with stress response pathways triggered by intra- or extracellular stress factors. Unfortunately, studies demonstrating the effects of osmolyte- and/or pH-induced stresses on bacterial persistence are largely missing. To fill this knowledge gap within the field, we studied the effects of various osmolytes and pH conditions on persistence with the use of phenotype microarrays and antibiotic tolerance assays. Although we found that a number of chemicals and pH environments, including urea, sodium nitrite, and acidic pH, significantly reduced persister formation in compared to no-osmolyte/no-buffer controls, this reduction in persister levels was less pronounced in late-stationary-phase cultures. Our results further demonstrated a positive correlation between cell growth and persister formation, which challenges the general notion in the field that slow-growing cultures have more persister cells than fast-growing cultures.
细菌持久型是一种表型变异体，它暂时对抗生素表现出非凡的耐受性。持久型与生物膜相关感染的顽固性有关；因此，对其生理学的全面了解可以改进针对此类感染的治疗策略。与持久型形成相关的机制被认为与由细胞内或细胞外应激因子引发的应激反应途径有关。不幸的是，目前缺乏证明渗透压剂和/或 pH 诱导应激对细菌持久性影响的研究。为了填补该领域的这一知识空白，我们使用表型微阵列和抗生素耐受性测定法研究了各种渗透压剂和 pH 条件对持久性的影响。尽管我们发现许多化学物质和 pH 环境，包括尿素、亚硝酸钠和酸性 pH，与无渗透压剂/无缓冲剂对照相比，显著降低了 中的持久型形成，但在晚期稳定期培养物中，持久型水平的降低并不那么明显。我们的结果进一步表明，细胞生长与持久型形成之间存在正相关，这挑战了该领域的一个普遍观点，即生长缓慢的培养物比生长迅速的培养物具有更多的持久型细胞。
