Listeria monocytogenes adapts to long-term stationary phase survival without compromising bacterial virulence

Abstract

Bacteria withstand starvation during long-term stationary phase through the acquisition of mutations that increase bacterial fitness. The evolution of the Growth Advantage in Stationary Phase (GASP) phenotype results in the ability of bacteria from an aged culture to outcompete bacteria from a younger culture when the two are mixed together. The GASP phenotype was first described for Escherichia coli but has not been examined for an environmental bacterial pathogen which must balance long-term survival strategies that promote fitness in the outside environment with those that promote fitness within the host. Listeria monocytogenes is an environmental bacterium that lives as a saprophyte in soil but is capable of replicating within the cytosol of mammalian cells. Here we demonstrate the ability of L. monocytogenes to express GASP via the acquisition of mutations during long-term stationary growth. L. monocytogenes GASP occurred through mechanisms that were both dependent and independent of the stress responsive alternative sigma factor SigB. Constitutive activation of the central virulence transcriptional regulator PrfA interfered with the development of GASP, however L. monocytogenes GASP cultures retained full virulence in mice. These results indicate that L. monocytogenes can accrue mutations that optimize fitness during long-term stationary growth without negatively impacting virulence.

The Listeria monocytogenes Hibernation-Promoting Factor Is Required for the Formation of 100S Ribosomes, Optimal Fitness, and Pathogenesis

“…For example, persister cells have been observed within normal, exponentially growing populations of bacteria and are thought to be small nongrowing subpopulations that are more resistant to insults than actively growing cells (35). In addition, L. monocytogenes has previously been shown to adapt to long-term stationary phase (called growth advantage at stationary phase [GASP]) in a partially B -dependent manner (36). The possibility that ribosome hibernation is con- nected to the persister cell or GASP phenotypes in L. monocytogenes warrants further investigation.…”

Occurrence of mutations impairing sigma factor B (SigB) function upon inactivation of Listeria monocytogenes genes encoding surface proteins

“…On the other hand, recent evidence shows that L. monocytogenes can adapt through selective mutations during in vitro and intra-host growth. Thus, L. monocytogenes possesses the ability to express growth advantage in the stationary phase through acquisition of mutations that optimize fitness during long-term stationary growth without negatively impacting virulence (Bruno & Freitag, 2011). Regarding in vivo adaptation, intra-host environment(s) were reported to stimulate rsbW mutations that impair SigB-dependent acid resistance together with invasion and growth of L. monocytogenes within macrophages and epithelial cells (Asakura et al, 2012).…”

Optimizing the Balance Between Host and Environmental Survival Skills: Lessons Learned from Listeria monocytogenes

“…Lastly, prfA * mutations appear to negatively impact the ability of L. monocytogenes to survive long periods of starvation [97]. The phenomenon known as ‘growth advantage in stationary phase’ (GASP) has recently been described for L. monocytogenes [97].…”