Recent Advances in Bacterial Persistence Mechanisms
Abstract
:1. Introduction
2. The Difference between Persistence and Resistance
3. Research on the Mechanism of Bacterial Persistence
3.1. Biofilm
3.2. Toxin–Antitoxin Modules
3.3. ppGpp and Stringent Response
3.4. SOS Response
4. Treatment of Persisters
Strategies | Targets/Options | Examples |
---|---|---|
Directly target the existing persisters | Bacterial membranes and cell walls | AM-0016 [72], boromycin [73] |
Drug combination | Daptomycin combined with ceftaroline [74] | |
Anti-cancer drugs | Mitomycin C [75] | |
Block persister formation | SOS response | Engineered bacteriophage [76] |
Biofilm formation | Quercetin [78], Dispersin B [79], peptide 1018 [80] | |
Before the infection | Vaccination [4] | |
Resuscitate persisters | Signaling pathways | Cis-2-decenoic acid [81] |
Stimulate antibiotic influx | Silver [83] |
5. Recent Progress of Technologies on Persister Studies
5.1. Enrichment Methods
5.2. From the Single-Cell Level
6. Remaining Challenges
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Technique | Principle | Advantages | Disadvantages | Application |
---|---|---|---|---|
BacDrop | Droplet-based technique for bacterial single-cell RNA-seq | Enables the massively parallel transcriptional profiling of millions of single bacterial cells | Prior knowledge of the genomes of interest species is required | Evaluate the heterogeneity in K. pneumoniae [96] |
Single-cell Raman spectroscopy | Based on the D2O absorption rate and carbon-deuterium Raman band which reflects the metabolic activity of a single cell | A powerful tool to identify persisters and normal bacteria at the single-cell level to allow further downstream analyses | It is challenging to directly detect Raman spectra with the presence of non-persister cells | Evaluate the biochemical properties of E. coli and persisters [88] |
A directly accessible femtoliter droplet array | A micron-sized femtoliter droplet array is fixed on a hydrophilic-in-hydrophobic micropatterned surface | (i) Individual droplets can be collected with a micropipette. (ii) This array can be used for gene and protein analyses | It is challenging to form a thin and uniform CYTOP layer as the surface | Collect the single cells of P. aeruginosa and microscopically observe them [94] |
Fluorescence dilution | Uses a susceptible strain harboring a plasmid that encodes a dose-dependent tetracycline-inducible gfp gene | Directly visualize and measure bacterial replication | The bacterial strain is inserted with a reporter | Monitor the lysis of intracellular S. aureus [7] |
Single-cell imaging using glass-bottom dishes and a nutrient agarose pad | A liquid culture is sandwiched in a glass bottom dish beneath the nutrient agarose pad which can maintain a consistent environment around the cells | Provides a long-term single-cell microscopy observation to capture high-quality quantitative information | The thickness of glass-bottom dishes needs to be adjusted to different microscopes | Characterize the lag phase and persistence of individual E. coli cells [100] |
Microfluidics coupled to fluorescence microscopy | Microfabricated chamber holds cells against the glass imaging surface to maintain a single focal plane during perfusion-based imaging experiments, and psulA::gfp plasmid is used as a fluorescent reporter | Acquire quantitative data and visualize the nucleoids in individual cells | It is limited to morphological observations | Analyze the persistence of wild-type E. coli to ofloxacin during stationary growth and follow the dynamics of the SOS response [68] |
ViSCAR | Useful information from complex time-lapse bacterial single-cell movies is transformed into a digital representation | It is an open-source software tool and provides multiple ways to visualize cell attribute trends | Data source should be based on the time-lapse microscopy live-cell imaging | Investigate the contribution of single-cell heterogeneity to emerging cellular phenotypes at different scales [103] |
Atomic force microscopy | Silicon nitride cantilevers are selected to perform force measurements on the bacterial surface | Studying persister phenotypic means from a morphological level | AMF is limited to characterizing changes that occur on the bacterial surface | Quantify the contributions of the membrane surface properties of MDR-E. coli strains [24] |
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Pan, X.; Liu, W.; Du, Q.; Zhang, H.; Han, D. Recent Advances in Bacterial Persistence Mechanisms. Int. J. Mol. Sci. 2023, 24, 14311. https://doi.org/10.3390/ijms241814311
Pan X, Liu W, Du Q, Zhang H, Han D. Recent Advances in Bacterial Persistence Mechanisms. International Journal of Molecular Sciences. 2023; 24(18):14311. https://doi.org/10.3390/ijms241814311
Chicago/Turabian StylePan, Xiaozhou, Wenxin Liu, Qingqing Du, Hong Zhang, and Dingding Han. 2023. "Recent Advances in Bacterial Persistence Mechanisms" International Journal of Molecular Sciences 24, no. 18: 14311. https://doi.org/10.3390/ijms241814311