This report describes infection of Drosophila by Listeria monocytogenes (L. monocytogenes), a Gram-positive facultative intracellular pathogen that causes disease (listerosis) in humans. L. monocytogenes first relies on its ability to escape the phagocytic vacuole and hijack its target's intracellular actin, allowing it to move within the cell and to spread to neighboring cells. It can survive at 40 degrees C, and thus is most frequently encountered as a food-borne pathogen.
Flies infected with L. monocytogenes die within 6-8 days, by which time the bacteria can have replicated to a population of up to 10 billion CFU. Both Toll pathway (FBgg0001059) mutants and Imd pathway mutants are more susceptible to L. monocytogenes, as are PGRP-LE mutants and autophagy-defective flies. As in humans, L. monocytogenes initially colonizes phagocytic hemocytes, then spreading to the fat body and epithelium. Adult and larval flies injected with L. monocytogenes respond with melanization, an immune response which produces both melanin and reactive oxygen species at the site of infection.
S2 cells (FBtc0000999), which have hemocyte-like gene expression, have been used to screen for anti-microbial genes in flies, as well as to screen L. monocytogenes mutants for virulence factors. Treating S2 cells with an actin polymerization inhibitor reduces the quantity of L. monocytogenes internalized by each cell.
[updated June 2019 by FlyBase; FBrf0222196]
Listeria infection can result either in a non-invasive self-limiting gastrointestinal form or in invasive clinical syndromes in at-risk categories of people (i.e. neonatal or maternofetal listeriosis, septicemia or meningoencephalitis). The cutaneous form of listeriosis is rare and mostly observed in people with at risk jobs (e.g. veterinarians and farmers exposed to animal products of conception). The non-invasive gastrointestinal form arises from non-specific symptoms (e.g. febrile gastroenteritis) and it often is of self-limiting nature with short incubation time. It usually occurs in healthy adults who have been exposed to high doses of the pathogen. Invasive syndromes yield mortality rates usually ranging 20-30%, despite adequate antibiotic treatment. (Lomonaco et al. 2015 and references therein; pubmed:26254574.)
The ability of L. monocytogenes to direct and exploit the polymerization of host cell actin for intracellular motility and cell-to-cell spread has been demonstrated to be a critical facet of mammalian pathogenesis. It has been hypothesized that bacterial cell-to-cell spread within mammals has evolved to enable the bacterium to 'outrun' adaptive immunity. (Mansfield et al. 2003, FBrf0167383.)
In vitro studies using cultured cells as a model host demonstrated that L. monocytogenes can enter professional phagocytes or nonphagocytic cells. Entry into nonphagocytic cells is dependent on surface proteins called internalins. Upon entry, a single-membrane vacuole forms around the bacterium. Secretion of a pore-forming cytotoxin, listeriolysin O (LLO), disrupts the phagosome membrane, freeing the bacterium into the cytosol where it can grow and divide. Expression of the actin-nucleating protein ActA facilitates polymerization of host actin at one pole of the bacterium, resulting in directional movement through the cytosol. Bacteria are able to spread to neighboring cells and escape from a second double-membrane phagosome into the cytosol of a new host cell. (Ayres et al. 2008 and citations therein, FBrf0205079.)
