Genetic determinants of persistence in Escherichia coli
The molecular mechanisms underlying bacterial persistence are not yet fully unraveled. However, there are several cellular pathways and functions linked to this form of phenotypic antibiotic tolerance (Figure 1).
A better understanding of these pathways could give rise to new strategies for eradicating chronic infections.
We are interested in the fundamental molecular signals that are involved in the formation, maintenance and awakening of bacterial persister cells. Recent reviews by the SPI group summarize new findings on persister cells and their tolerance to antibiotics (Van den Bergh et al. 2017). They also include an overview of the clinical aspects of persisters and their role in different chronic infections (Fauvart et al., 2011).
Our current research focuses on unraveling the molecular mechanisms of bacterial persistence in Escherichia coli, Pseudomonas aeruginosaand Staphylococcus aureus. We are trying to elucidate the molecular pathways by which persistence is mediated in these organisms. This is possible through the study of gene mutant libraries and screening of genome-wide single-gene knockout libraries. Persistence genes can be further analyzed and may yield novel targets for anti-persister therapies.
Verstraeten N., Knapen WJ., Kint CI., Liebens V., Van den Bergh B., Dewachter L., Michiels J.E., Fu Q., David C.C., Fierro A.C., Marchal K., Beirlant J., Versées W., Hofkens J., Jansen M., Fauvart M., Michiels J. (2015) Obg and membrane depolarization are part of a microbial bet-hedging strategy that leads to antibiotic tolerance. Mol. Cell. doi: 10.1016/j.molcel.2015.05.011 -- PubMed -- PDF -- Highlight in Nature Reviews Microbiology
Fauvart M., De Groote V.N., Michiels J. (2011). Role of persister cells in chronic infections: clinical relevance and perspectives on anti-persister therapies. J. Med. Microbiol. 60:699-709 -- PubMed -- PDF -- LabNews feature
De Groote V.N., Fauvart M., Kint C.I., Verstraeten N., Jans A., Cornelis P., Michiels J. (2011). Pseudomonas aeruginosa fosfomycin resistance mechanisms affect non-inherited fluoroquinolone tolerance. J. Med. Microbiol. -- PubMed -- PDF -- JMM Editorial -- SGM Press Release -- De Standaard (piece in Belgian newspaper) -- NRC Handelsblad (piece in Dutch newspaper)
De Groote, V.N., Verstraeten, N., Fauvart, M., Kint, C.I., Verbeeck, A.M., Beullens, S., Cornelis, P., Michiels, J. (2009). Novel persistence genes in Pseudomonas aeruginosaidentified by high-throughput screening. FEMS Microbiol. Lett. -- PubMed -- PDF -- Faculty of 1000 evaluation
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