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. Comparison between cells in the first day and after 7 days of incubation in mineral water, with biological triplicates.