Listeria monocytogenes — from saprophyte to intracellular pathogen

Abstract

Listeria monocytogenes is a bacterium that lives in the soil as a saprophyte but is capable of making the transition into a pathogen following its ingestion by susceptible humans or animals. Recent studies suggest that L. monocytogenes mediates its saprophyte-to-cytosolic-parasite transition through the careful modulation of the activity of a virulence regulatory protein known as PrfA, using a range of environmental cues that include available carbon sources. In this Progress article we describe the regulation of PrfA and its role in the L. monocytogenes transition from the saprophytic stage to the virulent intracellular stage.Humans are surrounded by an incredible abundance of diverse microorganisms. Estimates indicate that the flora living in the human mouth (>500 species) and gastrointestinal tract (>2,000 species) as well as on the skin (>180 species) 1-3 are vastly diverse, and that soil contains 10 6 -10 7 prokaryotic species per gram 4 . Given their vast abundance and diversity, it is reassuring to note that only a tiny proportion of these microorganisms are known to cause human disease. Recognizing that the environment provides a substantial reservoir of microorganisms, we pose two questions: what separates the potential pathogens from the nonpathogens and what types of adaptations enable a soil saprophyte to become a human pathogen?The bacterial pathogen Listeria monocytogenes is well adapted to both life in the soil and life in the cytosol of eukaryotic host cells. This Gram-positive saprophyte is ubiquitous in the environment, where it is thought to live off decaying plant material 5 . Following ingestion by a susceptible human, the bacterium is capable of making the transition to a physiological state that promotes bacterial survival and replication in host cells 6 . In healthy individuals, the disease caused by L. monocytogenes is usually restricted to a self-limiting gastroenteritis; however, in immunocompromised individuals and pregnant women, the bacterium is capable of causing systemic infections that lead to meningitis, encephalitis and, in the case of pregnant women, infection of the developing fetus, which can lead to abortion, stillbirth or neonatal infections 7 . The lifestyle switch to intracellular pathogen includes increases in the expression of gene products that are known to promote cell-to-cell spread and bacterial replication in the host cytosol; these gene products are generally expressed at low levels outside of the host 8 . How does L. monocytogenes implement the transition from life in the soil to life in the cell? Life in the outside environmentL. monocytogenes has been isolated from soil, silage, groundwater, sewage and vegetation 9 (FIG. 1). Whether it is associated with a lower eukaryotic host, such as a fungus, protist or nematode, has not been clearly established, although it is anticipated that the microorganism must frequently encounter these potential predators 10 . Substantial attention has been given to the ability of L. monocytogenes to survive in food proces...

Listeria monocytogenes infection in ruminants: Is there a link to the environment, food and human health? A review

“…However, both are hampered by the wide distribution of L. monocytogenes in the environment, where the bacterium commonly lives as a saprophyte (Weis and Seeliger, 1975;Vivant et al, 2013). When ingested by humans or animals it is capable of turning into an intracellular pathogen (Freitag et al, 2009).…”

“…Preventing the entry of L. monocytogenes into the food chain is challenging due to its ubiquity and high stress tolerance, allowing it to survive and persist under numerous environmental conditions (Freitag et al, 2009). However, it is still poorly understood how L. monocytogenes circulates between animals, humans and various environments (Fig.…”

Exploiting death: apoptotic immunity in microbial pathogenesis

“…In the case of Listeria monocytogenes, a virulent and lethal facultative intracellular bacterial pathogen, 39,42 the induction of host cell apoptosis appears to be important for bacterial pathogenicity. Listeria monocytogenes long has been known to trigger the apoptotic death of mammalian cells.…”

Signature tagged mutagenesis in the functional genetic analysis of gastrointestinal pathogens

“…[91][92][93][94] Infection occurs in step-wise manner consisting of entry into the host, lysis of the phagosomal vacuole, multiplication in the cytosol and direct cell to cell spread using actin based motility. 95 Each step is dependent on virulence factors which are located in a cluster of genes encoding a regulatory protein (PrfA), a phosphatidylinositol specific phospholipase C (PlcA), the hemolysin listeriolysin A (LLO), a metalloprotease (Mpl), an actin recruiting protein (ActA) and a lecithinase (PlcB). 95 A second locus encodes two proteins involved with invasion, InlA and InlB.…”