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Published on: February 14, 2025
Molecular mechanisms of bacterial persistence and phenotypic antibiotic resistance
Peng Cui1, Tao Xu1, Wen-hong Zhang1
1Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China.
Abstract:
Bacterial persistence refers to a state of reduced metabolic activity that endows a subpopulation of isogenic bacteria with multidrug tolerance. Persisters are phenotypic variants but not mutants. Since its discovery in 1944, bacterial persistence has not received enough attention until recently when its implications in persistent infections and biofilm infections become apparent. Much research has been done in recent years to investigate the mechanisms underlying bacterial persistence and phenotypic antibiotic resistance. The mechanisms of bacterial persistence are complex and the following pathways are involved in persister formation: toxin-antitoxin systems, reduced metabolism, energy production, protein and nucleic acid synthesis, DNA repair and protection, protein degradation, transporters/efflux systems, and transcriptional regulators etc. Although persistence mechanisms are conserved in terms of the gene function and pathways involved among different bacterial species, they may vary in gene homology and relative importance of a given pathway. For example, Escherichia coli toxin-antitoxin systems play an important role in persister formation, while Staphylococcus aureus persister formation does not appear to use toxin-antitoxin systems. Here we provide an update on recent progress in persistence mechanisms using E. coli and S. aureus as models, as well as discuss approaches in the treatment of persistent bacterial infections.
Insights
Bacterial persistence is a survival strategy where bacteria reduce metabolism for multidrug tolerance. Understanding these mechanisms is key to treating persistent infections.
Area of Science:
- Microbiology
- Molecular Biology
- Infectious Diseases
Background:
- Bacterial persistence, a state of reduced metabolic activity, confers multidrug tolerance to a subpopulation of bacteria.
- Persisters are phenotypic variants, not genetic mutants, crucial in persistent and biofilm infections.
- Recent research highlights the importance of bacterial persistence and phenotypic antibiotic resistance.
Purpose of the Study:
- To provide an update on recent progress in bacterial persistence mechanisms.
- To investigate the complex pathways involved in persister formation.
- To discuss treatment approaches for persistent bacterial infections.
Main Methods:
- Review of current literature on bacterial persistence mechanisms.
- Comparative analysis of persistence mechanisms in *Escherichia coli* and *Staphylococcus aureus*.
- Discussion of various pathways including toxin-antitoxin systems, metabolism, and transcriptional regulation.
Main Results:
- Bacterial persistence involves complex mechanisms including toxin-antitoxin systems, reduced metabolism, and transcriptional regulation.
- While persistence mechanisms are conserved, their specific gene homology and pathway importance vary between species.
- *Escherichia coli* relies heavily on toxin-antitoxin systems, whereas *Staphylococcus aureus* persister formation appears independent of them.
Conclusions:
- Bacterial persistence is a significant factor in antibiotic resistance and treatment failure.
- Understanding species-specific persistence mechanisms is crucial for developing effective therapeutic strategies.
- Further research into persistence pathways may lead to novel treatments for challenging bacterial infections.
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