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High-throughput Screening of Chemical Compounds to Elucidate Their Effects on Bacterial Persistence
Published on: February 23, 2021
In Vitro Studies of Persister Cells
Niilo Kaldalu1, Vasili Hauryliuk2,3,4, Kathryn Jane Turnbull3,4
1Institute of Technology, University of Tartu, Tartu, Estonia niilo.kaldalu@ut.ee.
Abstract:
Many bacterial pathogens can permanently colonize their host and establish either chronic or recurrent infections that the immune system and antimicrobial therapies fail to eradicate. Antibiotic persisters (persister cells) are believed to be among the factors that make these infections challenging. Persisters are subpopulations of bacteria which survive treatment with bactericidal antibiotics in otherwise antibiotic-sensitive cultures and were extensively studied in a hope to discover the mechanisms that cause treatment failures in chronically infected patients; however, most of these studies were conducted in the test tube. Research into antibiotic persistence has uncovered large intrapopulation heterogeneity of bacterial growth and regrowth but has not identified essential, dedicated molecular mechanisms of antibiotic persistence. Diverse factors and stresses that inhibit bacterial growth reduce killing of the bulk population and may also increase the persister subpopulation, implying that an array of mechanisms are present. Hopefully, further studies under conditions that simulate the key aspects of persistent infections will lead to identifying target mechanisms for effective therapeutic solutions.
Insights
Antibiotic persisters are bacterial subpopulations that survive antibiotic treatment, contributing to chronic infections. Further research simulating real infection conditions is needed to find therapeutic targets.
Area of Science:
- Microbiology
- Infectious Diseases
- Antimicrobial Resistance
Background:
- Chronic bacterial infections are difficult to eradicate with current therapies.
- Antibiotic persisters, a subpopulation of bacteria, survive antimicrobial treatment.
- Understanding persisters is crucial for addressing treatment failures in persistent infections.
Purpose of the Study:
- To investigate the role of antibiotic persisters in chronic and recurrent bacterial infections.
- To identify the molecular mechanisms underlying antibiotic persistence.
- To explore potential therapeutic strategies targeting persister cells.
Main Methods:
- Studied bacterial cultures under antibiotic treatment.
- Analyzed bacterial growth and regrowth heterogeneity.
- Investigated factors and stresses influencing persister subpopulations.
Main Results:
- Identified significant intrapopulation heterogeneity in bacterial growth and regrowth.
- Did not find essential, dedicated molecular mechanisms for antibiotic persistence.
- Observed that diverse factors inhibiting bacterial growth may increase persister subpopulations.
Conclusions:
- Antibiotic persistence is a complex phenomenon influenced by various factors and stresses.
- Current in vitro studies have limitations in fully understanding persister cell behavior.
- Further research simulating persistent infection conditions is necessary to identify therapeutic targets.
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