Persistence

Bacterial cells use a plethora of mechanisms to evade antibiotic killing. 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 withstand even high doses of antibiotics. For a review on how and why persisters can evade antibiotic killing see Wilmaerts, Windels et al. 2019, Dewachter et al. 2019, Verstraete et al. 2022 or Bollen, Louwagie et al. 2023. The persister phenotype is only temporary, and upon persister state exit, persisters re-initiate growth and are again susceptible to 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 pose a threat as they result in the recolonization of the infection site. Indeed, the recurrence of several chronic infections, such as lung infections in cystic fibrosis patients and tuberculosis, is associated with the presence of persister cells (see e.g. Fauvart, De Groote and Michiels 2011, Van den Bergh et al. 2017). 

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. Several research lines aim to detect key regulators of persistence, both in E. coli and in P. aeruginosa. Furthermore, these key regulators are subjected to further analysis with the aim of providing a better understanding of the underlying genetic and molecular mechanisms of persister formation (see e.g. Verstraeten, Knapen et al. 2015, Wilmaerts et al. 2018, Wilmaerts et al. 2022, Van den Bergh et al. 2022). 

In a parallel line of research, we are performing 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 (see e.g. Van den Bergh et al. 2016). We are additionally using experimental evolution to investigate how persistence affects the emergence of genetic resistance (see e.g. Windels, Michiels et al. 2019, Windels et al. 2024) and to assess the social-evolutionary dimension and ecological impact of persistence (see e.g. Windels et al. 2020, Windels et al. 2021). To translate our findings to clinically relevant conditions, we are using various model systems (see e.g. Verstraete et al. 2023) and we are investigating evolutionary patterns of resistance and persistence in longitudinal bacterial isolates from patients with suprapubic catheters. Highlighting the need to understand persistence and its clinical implications, we recently showed that while persistence can represent significant therapeutic challenges, it goes largely undetected by standard clinical antibiotic susceptibility assays (Van den Bergh, Ruelens et al. 2025). Finally, in a recently initiated line of research, we are examining the relation between the evolution of persistence and mutational robustness.