Antibiotic-tolerant persister cells


Research carried out by Bram Van den Bergh, Liselot Dewachter, Dorien Wilmaerts, Pauline Herpels, Etthel Windels, Laure Verstraete, Sang Nguyen, Elen Louwagie, Celien Bollen


Bacterial cells can evade antibiotic killing in several ways. A well-known strategy is antibiotic resistance, in which case the cells have acquired a genomic mutation enabling them to thrive in the presence of the antibiotic. In addition to resistance, every isogenic bacterial population harbours so-called persister cells. These persister cells are phenotypically different from their sensitive kin, and they can whithstand even high doses of antibiotics. For a review on how and why persisters can evade antibiotic killing see Wilmaerts, Windels et al. (2019). The persister phenotype is only temporarily, and upon persister state exit, persisters re-initiate growth and are again sensitive for antibiotics.

 

In healthy patients, it is assumed that the immune system can clear the residing persister cells after antibiotic treatment. In immunocompromised patients, or in biofilm-associated infections, persister cells impose a threat. The recurrence of several chronic infections, such as lung infections in cystic fibrosis patients, tuberculosis … are associated with the presence of persister cells (Fauvart et al. 2011). 

 

In the Michiels lab, persistence of the model bacterium Escherichia coli and of the opportunistic human pathogen Pseudomonas aeruginosa has been studied for many years. The focus is on a number of key regulators of persistence, both in E. coli and in P. aeruginosa, to yield a better understanding of the underlying genetic and molecular mechanisms. In addition, we are interested in key regulators of persister awakening. In ahother project, we perform evolution experiments to select for strains with high persistence levels. On the one hand, this helps us to unravel the genetic basis of persistence. On the other hand, it allows us to determine how persistence evolves in varying antibiotic treatment conditions. We additionally use experimental evolution to investigate how persistence affects the emergence of genetic resistance.The social-evolutionary impact of persistence is also studied within our group to gather a further fundamental understanding of this phenotype. Finally, in addition to these fundamental research topics, we also try to combat chronic infections through translational research.


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