Investigating the Effects of Osmolytes and Environmental pH on Bacterial Persisters

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 strategi...

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Bibliographic Details
Published in:Antimicrobial agents and chemotherapy 2020-04, Vol.64 (5)
Main Authors: Karki, Prashant, Mohiuddin, Sayed Golam, Kavousi, Pouria, Orman, Mehmet A
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents - pharmacology
Biofilms - drug effects
Buffers
Culture Media
Drug Resistance, Bacterial
Environment
Escherichia coli - drug effects
Escherichia coli - growth & development
Hydrogen-Ion Concentration
Microbial Sensitivity Tests
Microbial Viability - drug effects
Ofloxacin - pharmacology
Osmolar Concentration
Sodium Nitrite - pharmacology
Susceptibility
Urea - pharmacology
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Summary: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.
ISSN:0066-4804
1098-6596
DOI:10.1128/AAC.02393-19