The prfA gene product is a transcriptional activator of Listeria monocytogenes determinants pathogenicity. In this study, we provide direct evidence that the PrfA protein site-specific DNA-binding protein. Additionally, describe characterization two classes L. mutants which contain transposon insertions either in structural (exemplified by strain DP-L1075) or within promoter region DP-L973). Both are completely avirulent and secrete greatly reduced levels listeriolysin O...

During infections, CD4 + Foxp3 regulatory T (Treg) cells must control autoreactive conventional (Tconv) cell responses against self-peptide antigens while permitting those pathogen-derived “nonself” peptides. We defined the basis of this selectivity using mice in which Treg reactive to a single prostate-specific were selectively depleted. found that self-peptide-specific dispensable for Tconv matched specificity at homeostasis. However, they required such and prevent autoimmunity toward...

The facultative intracellular bacterial pathogen Listeria monocytogenes is capable of replicating within a broad range host cell types and species. We report here the establishment fruit fly Drosophila melanogaster as new model for exploration L. pathogenesis response to infection. was establishing lethal infections in adult flies larvae with extensive replication occurring before death. Bacteria were found cytosol insect phagocytic cells, directing actin polymerization. Bacterial gene...

Summary Expression of Type IV pili by the bacterial pathogen Neisseria gonorrhoeae appears to be essential for colonization human host. Several N. gene products have been recently identified which bear homology proteins involved in pilus assembly and protein export other systems. We report here isolation characterization transposon insertion mutants whose phenotypes indicate that pilF pilD are required gonoccocal biogenesis. Mutants lacking product, a pre‐pilin peptidase, were unable process...

Flagellin is the structural component of flagella produced by many pathogenic bacteria and a potent proinflammatory molecule that mediates these effects through Toll-like receptor (TLR) 5. In Listeria monocytogenes (LM), flagellin expression regulated temperature has been described as being shut off at 37°C. this study, we demonstrate TLR5-mediated cell activation maintained 37°C in some laboratory-adapted strains ≈ 20% LM clinical isolates. To determine role infection, targeted mutation...

Summary Expression of type IV pili appears to be a requisite determinant infectivity for the strict human pathogens Neisseria gonorrhoeae and meningitidis. The assembly these colonization factors is complex process. This report describes new pilus‐assembly gene, pilG , that immediately precedes gonococcal ( Gc) pilD gene encoding pre‐pilin leader peptidase. nucleotide sequence this region revealed single complete open reading frame whose derived polypeptide displayed significant identities...

Cell-mediated immunity is critical for host resistance to tuberculosis. T lymphocytes recognizing antigens presented by the major histocompatibility complex (MHC) class I and II molecules have been found be necessary control of mycobacterial infection. Mice genetically deficient in generation MHC Ia responses are susceptible Although soluble protein generally macrophages cells through molecules, infected with Mycobacterium tuberculosis or bacille Calmette-Guerin shown facilitate presentation...

Abstract We extended the use of Drosophila beyond being a model for signaling pathways required pattern recognition immune and show that fly can be used to identify genes pathogenesis host–pathogen interactions. performed forward genetic screen mutations altering sensitivity intracellular pathogen Listeria monocytogenes. recovered 18 mutants with increased susceptibility infection, none which were previously shown function in response. Using secondary screens, we divided these into two...

Listeria monocytogenes is a food-borne facultative intracellular pathogen. It widespread in the environment and has several distinct life-styles. The key transcriptional activator PrfA positively regulates L. virulence genes to mediate transition from extracellular, flagellum-propelled cell Here we report first evidence that also significant positive impact on extracellular biofilm formation. Mutants lacking prfA were defective surface-adhered DeltaprfA mutant exhibited wild-type flagellar...

The facultative intracellular bacterial pathogen Listeria monocytogenes dramatically increases the expression of several key virulence factors upon entry into host cell cytosol. actA, protein product which is required for cell-to-cell spread bacterium, expressed at low to undetectable levels in vitro and more than 200-fold after L. escape from phagosome. To identify that participate induction actA expression, mutants expressing high during growth were selected chemical mutagenesis. resulting...

Upon bacterial entry into the cytosol of infected mammalian host cells, central virulence regulator PrfA Listeria monocytogenes becomes activated and induces expression numerous factors which contribute to pathogenesis. The mechanism or signal by during course infection has not yet been determined; however, several amino acid substitutions within (known as PrfA* mutations) that appear lock protein a constitutively state have identified. In this study, activation statuses L. mutant strains...

ABSTRACT Listeria monocytogenes secretes two chitinases and one chitin binding protein. Mutants lacking chiA , chiB or lmo2467 exhibited normal growth in cultured cells but were defective for the livers spleens of mice. Mammals lack chitin; thus, L. may have adapted to recognize alternative substrates enhance pathogenesis.

PrfA is a key regulator of Listeria monocytogenes pathogenesis and induces the expression multiple virulence factors within infected host. post-translationally regulated such that protein becomes activated upon bacterial entry into cell cytosol. The signal triggers activation remains unknown, however mutations have been identified (prfA* mutations) lock high activity state. In this report we examine consequences constitutive on L. fitness both in vitro vivo. Whereas prfA* mutants were...

Preterm infants may be at risk of necrotizing enterocolitis (NEC) due to deficiency transforming growth factor-β 2 (TGF-β ) in the developing intestine. We hypothesized that low epithelial TGF-β expression preterm intestine and during NEC results from diminished autocrine induction these cells. Premature baboons delivered 67% gestation were treated per current norms for human infants. was diagnosed by clinical radiological findings. Inflammatory cytokines, , Smad7, Ski, strawberry notch N...

ABSTRACT Environmental pathogens survive and replicate within the outside environment while maintaining capacity to infect mammalian hosts. For some microorganisms, infection may be a relatively rare event. Understanding how environmental retain their ability cause disease provide insight into reservoirs of emerging infections. Listeria monocytogenes survives as saprophyte in soil but is capable causing serious invasive susceptible individuals. The bacterium secretes virulence factors that...

Microbes employ the thioredoxin system to defend against oxidative stress and ensure correct disulfide bonding maintain protein function. Listeria monocytogenes has been shown encode a putative thioredoxin, TrxA, but its biological roles underlying mechanisms remain unknown. Here, we showed that expression of L. TrxA is significantly induced in bacteria treated with thiol-specific oxidizing agent, diamide. Deletion trxA markedly compromised tolerance pathogen diamide, mainly impaired early...

Listeria monocytogenes is a Gram-positive facultative intracellular bacterial pathogen that invades mammalian cells and escapes from membrane-bound vacuoles to replicate within the host cell cytosol. Gene products required for growth spread adjacent are regulated by transcriptional activator known as PrfA. PrfA becomes activated following L. entry into cells, however signal stimulates activation has not yet been defined. Here we provide evidence secretion of small peptide pheromone, pPplA,...

ABSTRACT The ActA protein of Listeria monocytogenes is an essential virulence factor and required for intracellular bacterial motility cell-to-cell spread. plcB , cotranscribed with actA encodes a broad-specificity phospholipase C that contributes to lysis host cell vacuoles Construction transcriptional fusion between actA-plcB the green fluorescent gene Aequorea victoria has facilitated detailed examination patterns actA/plcB expression within infected tissue culture cells. began...

ABSTRACT Following entry into the host cytosol, bacterial pathogen Listeria monocytogenes dramatically increases expression of several key virulence factors. The actA , whose protein product is required for L . actin-based intracellular motility, increased by more than 200-fold in cytosolic bacteria comparison to broth-grown cultures. Two distinct promoter elements have been reported regulate expression. One located immediately upstream coding sequences, while second contributed mpl gene via...

Summary The PrfA transcriptional activator is an essential determinant of Listeria monocytogenes pathogenesis. prfA expression governed by three differentially regulated promoters: prfAP 1 and 2, which are located immediately upstream coding sequences, the adjacent plcA promoter via generation a – read‐through transcript. A series deletion mutants were constructed to assess roles 2. Elimination either or 2 resulted in altered regulation PrfA‐regulated genes after vitro growth. However, these...

ABSTRACT Listeria monocytogenes -infected phagocytes are present in the bloodstream of experimentally infected mice, but whether they play a role central nervous system (CNS) invasion is unclear. To test bacteria within leukocytes could establish CNS infection, mice were treated with gentamicin delivered by surgically implanted osmotic pumps. Bacterial inhibitory titers serum and plasma ranged from 1:16 to 1:256, essentially all viable leukocyte associated. Nevertheless, infection developed...

Listeria monocytogenes is an intracellular bacterial pathogen whose virulence depends on the regulated expression of numerous secreted factors. As for other gram-positive bacteria, many proteins by L. are translocated across membrane in unfolded state to compartment existing between and cell wall. This presents a challenging environment protein folding due its high density negative charge, concentrations cations, low pH. We recently identified PrsA2 as gene product required virulence. was...