Deep starvation induces loss of cell wall and dormancy in Listeria
Bacteria have developed multiple strategies, such as sporulation, to cope with environmental stress. Non-sporulating bacteria, however, may “hibernate” into a so-called viable but non-culturable (VBNC) state, where they are no longer able to grow in standard culture media and thus become undetectable by conventional growth-based methods. VBNC pathogens pose a significant risk for human and animal health as they can “wake up” back into a vegetative and virulent state. Although hundreds of bacterial species have been reported to enter a VBNC state in response to various stresses (e.g. thermal, osmotic, starvation, antibiotics), the molecular mechanisms governing this phenotypic switch remains largely elusive. Here, we report an in-depth characterization of the VBNC state transition process in the bacterial pathogen Listeria monocytogenes in response to nutritional deprivation. We found that starvation in mineral water drives L.monocytogenes into a VBNC state via a unique mechanism of cell wall shedding that generates cellwall-deficient coccoid forms. Transcriptomic and gene-targeted approaches revealed the stress response regulator SigB and the autolysin NamA as major mediators of cell wall loss and VBNC state transition. Overall design: Comparison between cells in the first day and after 7 days of incubation in mineral water, with biological triplicates.