Expression of Legionella pneumophila Virulence Traits in Response to Growth Conditions

Abstract

In nature, Legionella pneumophila replicates exclusively as an intracellular parasite of amoebae, but it also persists in the environment as a free-living microbe. Studies of how this opportunistic pathogen recognizes and responds to distinct extracellular and intracellular environments identified a link between the growth phase and expression of traits previously correlated with virulence. When cultured in broth, only post-exponential-phase L. pneumophila was sodium sensitive, cytotoxic, osmotically resistant, competent to evade macrophage lysosomes, infectious, and motile. Likewise, the L. pneumophila phenotype changed during growth in macrophages. During the intracellular replication period, this bacterium was sodium resistant and lacked flagella; concomitant with macrophage lysis, L. pneumophilabecame sodium sensitive and flagellated. Expression of the virulent phenotype was a response to starvation, since exponential-phaseL. pneumophila became cytotoxic, sodium sensitive, and motile after incubation in broth from stationary-phase cultures, except when it was supplemented with amino acids. Together, these data indicate that while nutrients are plentiful, intracellularL. pneumophila organisms are dedicated to replication; when amino acids become limiting, the progeny express virulence factors to escape the spent host, to disperse and survive in the aquatic environment, and to reestablish a protected intracellular niche favorable for growth.

Active and adaptive Legionella CRISPR‐Cas reveals a recurrent challenge to the pathogen

“…Our data also show that several cas genes, along with the CRISPR RNA, are up-regulated during postexponential growth (Fig. S3A), a growth phase that mimics the condition immediately prior to L. pneumophila lysis from the host cell and its transit through the extracellular environment (Byrne and Swanson, 1998). We next asked if these systems were indeed active (able to defend against protospacer-containing foreign DNA).…”

Early trafficking and intracellular replication of Legionella longbeachaea within an ER-derived late endosome-like phagosome

“…In vitro studies have shown that nutrient limitation at the post-exponential phase is the signal that triggers dramatic phenotypic modulations in L. pneumophila, and that is most likely to be the signal that triggers virulence traits at the post-exponential phase within macrophages (Byrne and Swanson, 1998;Hammer and Swanson, 1999;Bachman and Swanson, 2001;Hammer et al, 2002). It is well documented that the ability of L. pneumophila to replicate intracellularly is dependent on the bacterial growth phase (Byrne and Swanson, 1998).…”

“…It is well documented that the ability of the Philadelphiaderived Lp02 strain of L. pneumophila to replicate intracellularly is totally dependent on the bacterial growth phase (Byrne and Swanson, 1998;Hammer and Swanson, 1999;Bachman and Swanson, 2001;Hammer et al, 2002). While post-exponentialL.…”

“…While post-exponentialL. pneumophila evades endocytic fusion and replicates intracellularly, exponentially grown L. pneumophila Lp02 strain is completely defective in intracellular replication (Byrne and Swanson, 1998), and this is mediated by the stringent response to starvation for amino acids (Byrne and Swanson, 1998;Hammer and Swanson, 1999;Bachman and Swanson, 2001;Hammer et al, 2002). Therefore, we examined whether the growth phase of L. longbeachaea played a role in its ability to replicate intracellularly.…”

“…Upon entry into the post-exponential growth phase, L. pneumophila undergoes dramatic phenotypic and morphological changes and exhibits several virulence traits, including motility, stress resistance, pore-forming activity, and the ability to evade endocytic fusion and replicate intracellularly (Byrne and Swanson, 1998;Garduno et al, 1998;Alli et al, 2000;Garduno et al, 2002;Molmeret et al, 2002a;Hiltz et al, 2004). Whether other species of Legionella exhibit similar growth phase-dependent trigger of virulence traits is not known.…”