Targeting the Bet-Hedging Strategy with an Inhibitor of Bacterial Efflux Capacity Enhances Antibiotic Efficiency and Ameliorates Bacterial Persistence In Vitro
Abstract
:1. Introduction
2. Materials and Methods
2.1. Bacterial Strains and Reagents
2.2. Enumeration of Persister Populations
2.3. Evaluation of Bacterial Export Capacity
2.4. Treatment of Human PBMCs and NHBEC with Bacterial Natural Products
2.5. Histone H3 Acetylation and Caspase 3 Activation Assays
2.6. smFISH Image Analysis
2.7. Statistical Analysis
3. Results
3.1. Taxane-Based Reversal Agent, tRA99020, Acts as an Inhibitor of B. thailandensis Efflux Capacity and Potentiates Antibiotic-Mediated Killing of Bacterial Persister Populations
3.2. At 1 µM Concentration tRA99020 Stimulates Expression of Bacterial Persistence pks Gene in B. thailandensis Populations
3.3. Natural Products of Burkholderia PKS Function Modulate HDAC Activity in Live Human Peripheral Blood Mononuclear Cells
3.4. Natural Products of B. thailandensis PKS Function Inhibit Pro-Survival Mechanisms in Host Cells
3.5. Supplementation of Antibiotic Treatment with tRA99020 Agent Ameliorates the Cytotoxic Effect of Burkholderia spp. Natural Products on Host Cells
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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Morales, D.; Micheva-Viteva, S.; Adikari, S.; Werner, J.; Wolinsky, M.; Hong-Geller, E.; Kim, J.; Ojima, I. Targeting the Bet-Hedging Strategy with an Inhibitor of Bacterial Efflux Capacity Enhances Antibiotic Efficiency and Ameliorates Bacterial Persistence In Vitro. Microorganisms 2022, 10, 1966. https://doi.org/10.3390/microorganisms10101966
Morales D, Micheva-Viteva S, Adikari S, Werner J, Wolinsky M, Hong-Geller E, Kim J, Ojima I. Targeting the Bet-Hedging Strategy with an Inhibitor of Bacterial Efflux Capacity Enhances Antibiotic Efficiency and Ameliorates Bacterial Persistence In Vitro. Microorganisms. 2022; 10(10):1966. https://doi.org/10.3390/microorganisms10101966
Chicago/Turabian StyleMorales, Demosthenes, Sofiya Micheva-Viteva, Samantha Adikari, James Werner, Murray Wolinsky, Elizabeth Hong-Geller, Jinwoo Kim, and Iwao Ojima. 2022. "Targeting the Bet-Hedging Strategy with an Inhibitor of Bacterial Efflux Capacity Enhances Antibiotic Efficiency and Ameliorates Bacterial Persistence In Vitro" Microorganisms 10, no. 10: 1966. https://doi.org/10.3390/microorganisms10101966