Surface proteins and the pathogenic potential of Listeria monocytogenes (original) (raw)
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Classes and functions of Listeria monocytogenes surface proteins
Polish journal of microbiology / Polskie Towarzystwo Mikrobiologów = The Polish Society of Microbiologists, 2004
Listeria monocytogenes is an opportunistic pathogen that causes infections collectively termed listeriosis, which are related to the ingestion of food contaminated with these gram-positive rods. The pathogenicity of L. monocytogenes is determined by the following virulence factors: listeriolysin O, protein ActA, two phospholipases C, internalins (In1A and In1B), protein CwhA and a metalloprotease. The bacterium is a model organism in studies on the pathogenesis of intracellular parasites. It is able to penetrate, multiply and propagate in various types of eukaryotic cells and is also able to overcome the three main barriers encountered in the host: the intestinal barrier, the blood-brain barrier and the placenta. Based on L. monocytogenes genome sequence analysis 133 surface proteins have been identified. In particular, the large number of proteins covalently bound to murein sets L. monocytogenes apart from other gram-positive bacteria. The ability of this pathogen to multiply in va...
Infection and Immunity, 2003
The intracellular life of Listeria monocytogenes starts by a complex process of entry involving several bacterial ligands and eukaryotic receptors. In this work, we identified in silico from the sequence of the genome of L. monocytogenes a previously unknown gene designated lpeA (for lipoprotein promoting entry) encoding a 35-kDa protein homologous to PsaA, a lipoprotein belonging to the LraI family and implicated in the cell adherence of Streptococcus pneumoniae and related species. By constructing a mutant of L. monocytogenes in which lpeA is deleted (lpeA mutant), we show that the PsaA-like protein LpeA is not involved in bacterial adherence but is required for entry of L. monocytogenes in eukaryotic cells. In contrast to wild-type bacteria, mutant bacteria failed to invade the epithelial Caco-2 and hepatocyte TIB73 cell lines, as confirmed by confocal microscopy. The mutant bacteria rapidly penetrated in mouse bone marrow-derived macrophages. Surprisingly, lpeA mutant bacteria survive better in macrophages than do wild-type bacteria. This was correlated with a weak exacerbation of virulence of the lpeA mutant in the mouse. LpeA is therefore a novel invasin favoring the entry of L. monocytogenes into nonprofessional phagocytes but not its invasion of macrophages. This is the first report of a lipoprotein promoting cell invasion of an intracellular pathogen.
Journal of Biological Chemistry, 2018
Outer membrane vesicles produced by Gram-negative bacteria have been studied for half a century but the possibility that Gram-positive bacteria secrete extracellular vesicles (EVs) was not pursued until recently due to the assumption that the thick peptidoglycan cell wall would prevent their release to the environment. However, following their discovery in fungi, which also have cell walls, EVs have now been described for a variety of Gram-positive bacteria. EVs purified from Gram-positive bacteria are implicated in virulence, toxin release, and transference to host cells, eliciting immune responses, and spread of antibiotic resistance. Listeria monocytogenes is a Gram-positive bacterium that causes listeriosis. Here we report that L. monocytogenes produces EVs with diameters ranging from 20 to 200 nm, containing the pore-forming toxin listeriolysin O (LLO) and phosphatidylinositol-specific phospholipase C (PI-PLC). Cell-free EV preparations were toxic to mammalian cells, the murine macrophage cell line J774.16, in a LLO-dependent manner, evidencing EV biological activity. The deletion of plcA increased EV toxicity, suggesting PI-PLC reduced LLO activity. Using simultaneous metabolite, protein, and lipid extraction (MPLEx) multiomics we characterized protein, lipid, and metabolite composition of bacterial cells and secreted EVs and found that EVs carry the majority of listerial virulence proteins. Using immunogold EM we detected LLO at several organelles within infected human epithelial cells and with high-resolution fluorescence imaging we show that dynamic lipid structures are released from L. monocytogenes during infection. Our findings demonstrate that L. monocytogenes uses EVs for toxin release and implicate these structures in mammalian cytotoxicity. The pathogenic Gram-positive bacterium Listeria monocytogenes is the etiological agent of listeriosis, a disease with serious consequences for pregnant women, newborns, and immunocompromised persons. Healthy individuals who have ingested large amounts of L. monocytogenes can suffer from gastroenteritis when the bacterium passes through the gastrointestinal barrier (1-4). L. monocytogenes can cause spontaneous abortions in pregnant women and meningoencephalitis by crossing the placental and blood-brain barriers, respectively (5). To invade cells, cross these barriers, and evade the immune system, L. monocytogenes has a sophisticated intracellular life cycle and pathogenic strategy (6, 7). Initially, L. monocytogenes invades various cell types, including nonphagocytic cells, by utilizing two internalins, internalin A (InlA) and internalin B (InlB), with a minor contribution by the pore-forming toxin listeriolysin O (LLO), 7 to induce uptake of the bacterium (1, 5, 8-11). Once internalized in the host vacuole, L. monocytogenes employs LLO, phosphatidylcholinespecific phospholipase (PC-PLC), and phosphatidylinositolspecific phospholipase C (PI-PLC) to disrupt the single vacuolar membrane, releasing the bacterium into the cytoplasm The authors declare that they have no conflicts of interest with the contents of this article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This article contains Movie S1, Tables S1-S4, and Figs. S1-S4. Multiomics data were deposited in the MassIVE repository under accession numbers MSV000081402, MSV000081403, and MSV000081404.
Crossing the Intestinal Barrier via Listeria Adhesion Protein and Internalin A
Trends in Microbiology, 2019
The intestinal epithelial cell lining provides the first line of defense, yet foodborne pathogens such as Listeria monocytogenes can overcome this barrier; however, the underlying mechanism is not well understood. Though the host M cells in Peyer's patch and the bacterial invasion protein internalin A (InlA) are involved, L. monocytogenes can cross the gut barrier in their absence. The interaction of Listeria adhesion protein (LAP) with the host cell receptor (heat shock protein 60) disrupts the epithelial barrier, promoting bacterial translocation. InlA aids L. monocytogenes transcytosis via interaction with the E-cadherin receptor, which is facilitated by epithelial cell extrusion and goblet cell exocytosis; however, LAP-induced cell junction opening may be an alternative bacterial strategy for InlA access to E-cadherin and its translocation. Here, we summarize the strategies that L. monocytogenes employs to circumvent the intestinal epithelial barrier and compare and contrast these strategies with other enteric bacterial pathogens. Additionally, we provide implications of recent findings for food safety regulations. Foodborne Listeria monocytogenes Infection L. monocytogenes is an opportunistic and highly invasive foodborne bacterial pathogen. It was first isolated from rabbits [1]. In the early part of the 20th century the pathogen was recognized as an animal pathogen and was found to infect ruminants, predominantly cows and sheep, causing circling disease and abortion. Animals suffer from ataxia, anorexia, depression, lethargy, septicemia, meningitis, head tilt, and encephalitis, which result in the loss of balance, causing the animals to walk in a circle [2]. L. monocytogenes was not recognized as a human foodborne pathogen until early in the 1980s, when multiple outbreaks were reported in North America [3,4]. Researchers began to link this pathogen's association with soil, manure, decaying vegetation, and the environment [5,6] as the primary mode of transmission to foods. L. monocytogenes is highly adaptable and uses sophisticated regulatory mechanisms to make the transition from a soil-living saprophyte to an invasive pathogen in humans and animals during foodborne infection [7,8]. The breaching of barrierssuch as the host intestinal barrier [9-11], the blood-brain barrier [12,13], and the placental barrier [14,15]is a key mechanism used by the intracellular bacterium L. monocytogenes [16]. Pregnant women, fetuses, newborn children, adults aged 65 and older, and people with weakened immune systems are most at risk and suffer from severe illnesses, including sepsis, meningitis, or encephalitis, often with lifelong consequences. Listeriosis outbreaks are often associated with ready-to-eat (RTE) products, including deli meats, hot dogs, liver pâté, smoked fish, soft cheeses prepared from unpasteurized milk, ice cream, coleslaw, and produce such as frozen vegetables, cantaloupe, and apple [3]. In the USA, about 1600 people are infected each year, causing an estimated 260 deaths [17]. Among Highlights Intestinal epithelial cells are the first line of defense against enteric pathogens. Bacterial pathogens such as L. monocytogenes have evolved sophisticated mechanisms to breach this barrier. L. monocytogenes invasion protein internalin A (InlA) targets its basolateral receptor, E-cadherin, by host intrinsic mechanisms, the epithelial cell extrusion and goblet cell exocytosis allows its transcytosis across the intestinal barrier. The Listeria adhesion protein (LAP) engages its surface receptor, Hsp60, and initiates a complex signaling cascade, leading to cellular redistribution of cell-to-cell junctional proteins for L. monocytogenes translocation.
LPXTG Protein InlJ, a Newly Identified Internalin Involved in Listeria monocytogenes Virulence
Infection and Immunity, 2005
Listeria monocytogenes expresses surface proteins covalently anchored to the peptidoglycan by sortase enzymes. Inactivation of srtA attenuates Listeria virulence in mice (H. Bierne, S. K. Mazmanian, M. Trost, M. G. Pucciarelli, G. Liu, P. Dehoux, L. Jansch, F. Garcia-del Portillo, O. Schneewind, and P. Cossart, Mol. Microbiol. 43:869-881, 2002)
Molecular aspects of Listeria monocytogenes infection
Polish journal of microbiology / Polskie Towarzystwo Mikrobiologów = The Polish Society of Microbiologists, 2004
Listeria monocytogenes, a food-borne intracellular animal and human pathogen, interacts with infected host cells both prior to entry and during the intracellular phase of infection. This review is focused on the role of secreted proteins, including listeriolysin O and two distinct phospholipases C, in modulating the signal transduction of infected cells.
Molecular determinants of Listeria monocytogenes pathogenesis
Infection and immunity, 1992
Listeria monocytogenes is a rapidly growing, gram-positive, food-borne human and animal pathogen responsible for serious infections in immunocompromised individuals and pregnant women (17). The murine model of listeriosis has received enormous attention over the years because of the utility of L. monocytogenes as a model pathogen to study cell-mediated immunity. In fact, much of our current understanding of cell-mediated immunity, such as the concept of the activated macrophage, has its roots in the study of murine listeriosis . The beauty of the murine model is that it provides a highly reproducible system for the quantitation of L. monocytogenes virulence. However, until relatively recently almost nothing was known about the cell biology of intracellular growth or bacterial determinants of pathogenicity.
Listeriosis is a food-borne disease caused by the opportunistic pathogen Listeria monocytogenes. Internalization of Listeria into non phagocytic cells is the crucial step in the pathogenesis of listeriosis. This process is mediated by a group of 25 surface and secretory proteins called internalins. The majority of internalins share an N-terminal superdomain that comprises N-signal peptide, N-cap, leucin rich repeats and inter-repeat region. The attachment of these proteins to the bacterial surface depends on its C-terminal domain. Members containing LPXTG domain can covalently attach to the peptidoglycan moieties, while GW-or WxL containing members, non-covalently, bind lipoteichoic acid fragments. On the other hand, proteins lacking the C-terminal domain are secreted outside the cell. Internalins expression is regulated by the transcriptional activator PrfA and the stress responsive sigma factor σ B . Moreover, Quorum sensing peptides might be involved in the regulation of internal...
Current Microbiology, 2014
Internalins comprise a class of Listeria monocytogenes proteins responsible for activation of signalling pathways leading to phagocytic uptake of the bacterium by the host cell. In this paper, a possible role of Lmo0171-a new member of the internalin family was investigated. Disruption of the lmo0171 gene resulted in important cell morphology alterations along with a decrease in the ability to invade three eukaryotic cell lines, that is Int407, Hep-2 and HeLa and diminished adhesion efficiency to int407, thereby suggesting bifunctionality of the newly characterised Lmo0171 internalin.