The Dynamic Transition of Persistence toward the Viable but Nonculturable State during Stationary Phase Is Driven by Protein Aggregation

Abstract

While persistence and the viable but nonculturable (VBNC) state are currently investigated in isolation, our results strongly indicate that these phenotypes represent different stages of the same dormancy program and that they should therefore be studied within the same conceptual framework. Moreover, we show here for the first time that the dynamics of protein aggregation perfectly match the onset and further development of bacterial dormancy and that different dormant phenotypes are linked to different stages of protein aggregation.

Transcription-coupled DNA repair underlies variation in persister awakening and the emergence of resistance

“…In addition, persisters formed by the pore-forming HokB toxin were found to wake up based on pore disassembly via a combination of DsbC-mediated monomerization and DegQmediated peptide degradation, followed by membrane repolarization (Wilmaerts et al, 2019a). Furthermore, protein aggregate formation and removal were shown to be correlated with persister state entry and exit (Pu et al, 2019;Bollen et al, 2021;Dewachter et al, 2021). Based on these findings, we can infer that other persister formation pathways should be reverted to initiate persister state exit.…”

Host Cell Oxidative Stress Induces Dormant Staphylococcus aureus Persisters

“…Aggregates of proteins cause an important absorbance of light and can be observed as dark foci in bright-field (or phase-contrast) images ( 68 , 69 ). S. aureus cells from planktonic cultures or recovered from macrophages were fixed with 3.7% paraformaldehyde for 5 min.…”

A Shift in Perspective: A Role for the Type I Toxin TisB as Persistence-Stabilizing Factor

“…It came to our attention that a persistence-stabilizing function of type I toxins might be in support of the “dormancy continuum hypothesis” ( Ayrapetyan et al, 2015 , 2018 ). Similarly to what was suggested for protein aggregation ( Pu et al, 2019 ; Dewachter et al, 2021 ), accumulation of TisB and its concomitant effects might not only stabilize the persister state and affect dormancy depth, but also enable transition from a persister to a viable but non-culturable (VBNC) state. Further experiments are clearly needed to elucidate the role that type I toxins play in bacterial dormancy in response to environmental stress.…”