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...

Summary The study of T cell memory and the target of vaccine design has focused on memory subsumed by T cells bearing the αβ T cell receptor. Alternatively, γδ T cells are thought to provide rapid immunity particularly at mucosal borders. Here we have shown that a distinct subset of mucosal γδ T cells mounts an immune response to oral Listeria monocytogenes (Lm) infection leading to the development of multifunctional memory T cells in the murine intestinal mucosa that is capable of simultaneously producing interferon-γ and interleukin-17A. Challenge infection with oral Lm, but not oral Salmonella or intravenous Lm, induced rapid expansion of memory γδ T cells suggesting contextual specificity to the priming pathogen. Importantly, memory γδ T cells were able to provide enhanced protection against infection. These findings illustrate a previously unrecognized role for γδ T cells with hallmarks of adaptive immunity in the intestinal mucosa.

Expression of Type IV pili by the bacterial pathogen Neisseria gonorrhoeae appears to be essential for colonization of the human host. Several N. gonorrhoeae gene products have been recently identified which bear homology to proteins involved in pilus assembly and protein export in other bacterial systems. We report here the isolation and characterization of transposon insertion mutants in N. gonorrhoeae whose phenotypes indicate that the N. gonorrhoeae pilF and pilD gene products are required for gonoccocal pilus biogenesis. Mutants lacking the pilD gene product, a pre-pilin peptidase, were unable to process the pre-pilin subunit into pilin and thus were non-piliated. pilF mutants processed pilin but did not assemble the mature subunit. Both classes of mutants released S-pilin, a soluble, truncated form of the pilin subunit previously correlated with defects in pilus assembly. In addition, mutants containing transposon insertions in pilD or in a downstream gene, orfX, exhibited a severely restricted growth phenotype. Deletion analysis of pilD indicated that the poor growth phenotype observed for the pilD transposon mutants was a result of polar effects of the insertions on orfX expression. orfX encodes a predicted polypeptide of 23 kDa which contains a consensus nucleotide-binding domain and has apparent homologues in Pseudomonas aeruginosa, Pseudomonas putida, Thermus thermophilus, and the eukaryote Caenorhabditis elegans. Although expression of orfX and pilD appears to be transcriptionally coupled, mutants containing transposon insertions in orfX expressed pili. Unlike either pilF or pilD mutants, orfX mutants were also competent for DNA transformation.

No abstract