Listeria monocytogenes Surface Proteins: from Genome Predictions to Function

SUMMARY The genome of the human food-borne pathogen Listeria monocytogenes is predicted to encode a high number of surface proteins. This abundance likely reflects the ability of this bacterium to survive in diverse environments, including soil, food, and the human host. This review focuses on the various mechanisms by which listerial proteins are attached at the bacterial surface and their many functions, including peptidoglycan metabolism, protein processing, adhesion to host cells, and invasion of host tissues. Extensive in silico analysis of the domains or motifs present in these mosaic proteins reveals that diverse structural features allow the surface proteome to interact with diverse bacterial or host components. This diversity offers new clues about the molecular bases of Listeria pathogenesis.

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Invasion mechanisms of Gram-positive pathogenic cocci

Thrombosis and Haemostasis ◽

10.1160/th07-03-0179 ◽

2007 ◽

Vol 98 (09) ◽

pp. 488-496 ◽

Cited By ~ 47

Author(s):

Patric Nitsche-Schmitz ◽

Manfred Rohde ◽

Gursharan Chhatwal

Keyword(s):

Surface Proteins ◽

Host Cells ◽

Human Pathogens ◽

Gram Positive ◽

Bacterial Surface ◽

Surface Receptors ◽

Major Threat ◽

Invasion Mechanisms ◽

Invasive Infections ◽

Gram Positive Cocci

SummaryGram-positive cocci are important human pathogens. Streptococci and staphylococci in particular are a major threat to human health,since they cause a variety of serious invasive infections. Their invasion into normally sterile sites of the host depends on elaborated bacterial mechanisms that involve adhesion to the host tissue, its degradation, internalisation by host cells, and passage through epithelia and endothelia. Interactions of bacterial surface proteins with proteins of the host’s extracellular matrix as well as with cell surface receptors are crucial factors in these processes, and some of the key mechanisms are similar in many pathogenic Gram-positive cocci.Therapies that interfere with these mechanisms may become efficient alternatives to today’s antibiotic treatments.

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Vertical Transmission of Listeria monocytogenes: Probing the Balance between Protection from Pathogens and Fetal Tolerance

Pathogens ◽

10.3390/pathogens7020052 ◽

2018 ◽

Vol 7 (2) ◽

pp. 52 ◽

Cited By ~ 10

Author(s):

Nicole Lamond ◽

Nancy Freitag

Keyword(s):

Cell Culture ◽

Listeria Monocytogenes ◽

Animal Models ◽

Vertical Transmission ◽

Surface Proteins ◽

Placental Barrier ◽

Bacterial Surface ◽

Organ Models ◽

The Many

Protection of the developing fetus from pathogens is one of the many critical roles of the placenta. Listeria monocytogenes is one of a select number of pathogens that can cross the placental barrier and cause significant harm to the fetus, leading to spontaneous abortion, stillbirth, preterm labor, and disseminated neonate infection despite antibiotic treatment. Such severe outcomes serve to highlight the importance of understanding how L. monocytogenes mediates infiltration of the placental barrier. Here, we review what is currently known regarding vertical transmission of L. monocytogenes as a result of cell culture and animal models of infection. In vitro cell culture and organ models have been useful for the identification of L. monocytogenes virulence factors that contribute to placental invasion. Examples include members of the Internalin family of bacterial surface proteins such as Interalin (Inl)A, InlB, and InlP that promote invasion of cells at the maternal-fetal interface. A number of animal models have been used to interrogate L. monocytogenes vertical transmission, including mice, guinea pigs, gerbils, and non-human primates; each of these models has advantages while still not providing a comprehensive understanding of L. monocytogenes invasion of the human placenta and/or fetus. These models do, however, allow for the molecular investigation of the balance between fetal tolerance and immune protection from L. monocytogenes during pregnancy.

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REALIS: Postgenomic Analysis ofListeria monocytogenes

Comparative and Functional Genomics ◽

10.1002/cfg.137 ◽

2002 ◽

Vol 3 (1) ◽

pp. 32-34 ◽

Cited By ~ 1

Author(s):

Uwe Kärst ◽

The REALIS Consortium

Keyword(s):

Listeria Monocytogenes ◽

Opportunistic Infections ◽

External Environment ◽

Low Ph ◽

Health Care Managers ◽

Food Borne ◽

Contaminated Food ◽

Oflisteria Monocytogenes ◽

Immunocompromised Hosts ◽

Host Tissues

Listeria monocytogenesis a remarkably successful food-borne pathogen. It is capable a) of surviving and proliferating under conditions that exist within the food chain, such as at low temperatures, high salt and low pH and b) of colonizing animal host tissues after ingestion of contaminated food, causing opportunistic infections mainly, but not exclusively, in immunocompromised hosts. The ultimate goals of REALIS are two fold: Firstly, it aims to completely decipher all genes required for survival in and adaptation ofListeria monocytogenesto two very different environments, ie., the infected host and the external environment. Secondly, using genomics and postgenomic tools, REALIS seeks to precisely address fundamental questions regarding evolutionary relationships between pathogenic and non-pathogenic Listeria and to define qualities of particularly successful clonal pathovariants in causing disease. This project will provide both industry and health care managers with rational approaches to curbing food-borne contamination, minimising risks of infection and providing novel pharmacological approaches for halting the fulminant course of infection.

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Detoxification of methylglyoxal by the glyoxalase system is required for glutathione availability and virulence activation in Listeria monocytogenes

PLoS Pathogens ◽

10.1371/journal.ppat.1009819 ◽

2021 ◽

Vol 17 (8) ◽

pp. e1009819

Author(s):

Andrea Anaya-Sanchez ◽

Ying Feng ◽

John C. Berude ◽

Daniel A. Portnoy

Keyword(s):

Listeria Monocytogenes ◽

Transcriptional Activation ◽

Protein Glycation ◽

Host Cells ◽

Intracellular Pathogen ◽

Cell Monolayers ◽

Food Borne ◽

Virulence Regulator ◽

Allosteric Activator

Listeria monocytogenes is a Gram-positive, food-borne pathogen that lives a biphasic lifestyle, cycling between the environment and as a facultative intracellular pathogen of mammals. Upon entry into host cells, L. monocytogenes upregulates expression of glutathione synthase (GshF) and its product, glutathione (GSH), which is an allosteric activator of the master virulence regulator PrfA. Although gshF mutants are highly attenuated for virulence in mice and form very small plaques in host cell monolayers, these virulence defects can be fully rescued by mutations that lock PrfA in its active conformation, referred to as PrfA*. While PrfA activation can be recapitulated in vitro by the addition of reducing agents, the precise biological cue(s) experienced by L. monocytogenes that lead to PrfA activation are not known. Here we performed a genetic screen to identify additional small-plaque mutants that were rescued by PrfA* and identified gloA, which encodes glyoxalase A, a component of a GSH-dependent methylglyoxal (MG) detoxification system. MG is a toxic byproduct of metabolism produced by both the host and pathogen, which if accumulated, causes DNA damage and protein glycation. As a facultative intracellular pathogen, L. monocytogenes must protect itself from MG produced by its own metabolic processes and that of its host. We report that gloA mutants grow normally in broth, are sensitive to exogenous MG and severely attenuated upon IV infection in mice, but are fully rescued for virulence in a PrfA* background. We demonstrate that transcriptional activation of gshF increased upon MG challenge in vitro, and while this resulted in higher levels of GSH for wild-type L. monocytogenes, the glyoxalase mutants had decreased levels of GSH, presumably due to the accumulation of the GSH-MG hemithioacetal adduct. These data suggest that MG acts as a host cue that leads to GSH production and activation of PrfA.

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Cyclic Dimeric GMP Signaling Regulates Intracellular Aggregation, Sessility, and Growth of Ehrlichia chaffeensis

Infection and Immunity ◽

10.1128/iai.05320-11 ◽

2011 ◽

Vol 79 (10) ◽

pp. 3905-3912 ◽

Cited By ~ 13

Author(s):

Yumi Kumagai ◽

Junji Matsuo ◽

Zhihui Cheng ◽

Yoshihiro Hayakawa ◽

Yasuko Rikihisa

Keyword(s):

Serine Protease ◽

Serine Proteases ◽

Matrix Protein ◽

Response Regulator ◽

Bacterial Biofilm ◽

Surface Proteins ◽

Host Cells ◽

Ehrlichia Chaffeensis ◽

Content Type ◽

Bacterial Surface

ABSTRACTCyclic dimeric GMP (c-di-GMP), a bacterial second messenger, is known to regulate bacterial biofilm and sessility. Replication of an obligatory intracellular pathogen,Ehrlichia chaffeensis, is characterized by formation of bacterial aggregates called morulae inside membrane-bound inclusions. WhenE. chaffeensismatures into an infectious form, morulae become loose to allow bacteria to exit from host cells to infect adjacent cells.E. chaffeensisexpresses a sensor kinase, PleC, and a cognate response regulator, PleD, which can produce c-di-GMP. A hydrophobic c-di-GMP antagonist, 2′-O-di(tert-butyldimethysilyl)-c-di-GMP (CDGA) inhibitsE. chaffeensisinternalization into host cells by facilitating degradation of some bacterial surface proteins via endogenous serine proteases. In the present study, we found that PleC and PleD were upregulated synchronously during exponential growth of bacteria, concomitant with increased morula size. While CDGA did not affect host cells, when infected cells were treated with CDGA, bacterial proliferation was inhibited, morulae became less compact, and the intracellular movement of bacteria was enhanced. Concurrently, CDGA treatment facilitated the extracellular release of bacteria with lower infectivity than those spontaneously released from sham-treated cells. Addition of CDGA to isolated inclusions induced dispersion of the morulae, degradation of an inclusion matrix protein TRP120, and bacterial intrainclusion movement, all of which were blocked by a serine protease inhibitor. These results suggest that c-di-GMP signaling regulates aggregation and sessility ofE. chaffeensiswithin the inclusion through stabilization of matrix proteins by preventing the serine protease activity, which is associated with bacterial intracellular proliferation and maturation.

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Gene Fragments Distinguishing an Epidemic-Associated Strain from a Virulent Prototype Strain ofListeria monocytogenes Belong to a Distinct Functional Subset of Genes and Partially Cross-Hybridize with OtherListeria Species

Infection and Immunity ◽

10.1128/iai.69.6.3972-3979.2001 ◽

2001 ◽

Vol 69 (6) ◽

pp. 3972-3979 ◽

Cited By ~ 43

Author(s):

Martin Herd ◽

Christine Kocks

Keyword(s):

Southern Hybridization ◽

Immune Escape ◽

The United States ◽

Prototype Strain ◽

Surface Proteins ◽

Bacterial Surface ◽

Food Borne ◽

Starting Point ◽

Serotype 4B ◽

Oflisteria Monocytogenes

ABSTRACT Most major food-borne outbreaks of listeriosis in Europe and in the United States have been caused by genetically closely relatedListeria monocytogenes strains of serotype 4b. In order to assess whether genomic loci exist that could underlie this increased epidemic potential, we subtracted the genome of the virulent prototypeL. monocytogenes strain EGD from a prototype epidemic strain. A total of 39 DNA fragments corresponding to 20% of an estimated total of 150 to 190 kb of differential genome material were isolated. For 21 of these fragments, no function on the basis of homology could be predicted. Of the remaining 18 fragments, 15 had homologies to bacterial surface proteins, some of which have been implicated in virulence mechanisms such as cell invasion, adhesion, or immune escape. Southern hybridization of arrays containing the epidemic-clone-specific DNA segments with genomic DNA of differentL. monocytogenes strains was consistent with the current lineage division. Surprisingly, however, some of the fragments hybridized in a mosaic-like fashion to genomes of two otherListeria species, the animal pathogen L. ivanovii and the nonpathogen L. innocua. Taken together, our results provide a starting point for the identification of epidemic-trait-associated genes.

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LPXTG Protein InlJ, a Newly Identified Internalin Involved in Listeria monocytogenes Virulence

Infection and Immunity ◽

10.1128/iai.73.10.6912-6922.2005 ◽

2005 ◽

Vol 73 (10) ◽

pp. 6912-6922 ◽

Cited By ~ 105

Author(s):

Christophe Sabet ◽

Marc Lecuit ◽

Didier Cabanes ◽

Pascale Cossart ◽

Hélène Bierne

Keyword(s):

Listeria Monocytogenes ◽

Deletion Mutant ◽

Consensus Sequence ◽

Surface Proteins ◽

Leucine Rich Repeat ◽

Food Borne ◽

Oral Inoculation ◽

Protein Encoding ◽

Encoding Genes ◽

Lrr Protein

ABSTRACTListeria monocytogenesexpresses surface proteins covalently anchored to the peptidoglycan by sortase enzymes. Inactivation ofsrtAattenuatesListeriavirulence 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). We show here that ansrtAmutant is more attenuated than an internalin mutant in orally infected guinea pigs and transgenic mice expressing human E-cadherin (hEcad mice), indicating the involvement of other SrtA substrates, LPXTG proteins, in food-borne listeriosis. Data recently generated with a listerial DNA macroarray identified two LPXTG protein-encoding genes present in the genomes ofL. monocytogenesstrains and absent from all otherListeriaspecies,inlI(lmo0333) andinlJ(lmo2821). They also revealed two other LPXTG protein-encoding genes, ORF29 and ORF2568, present only in a subclass ofL. monocytogenesserovars, including the epidemic serovar 4b. We report here that aninlJdeletion mutant, in contrast toinlIand ORF29 mutants, is significantly attenuated in virulence after intravenous infection of mice or oral inoculation of hEcad mice. Interestingly, a ΔORF2568 strain showed a slight increase in virulence.inlJencodes a leucine-rich repeat (LRR) protein that is structurally related to the listerial invasion factor internalin. However, the consensus sequence of the InlJ LRR defines a novel subfamily of cysteine-containing LRRs in bacteria. In conclusion, this postgenomic approach identified InlJ as a new virulence factor among the proteins belonging to the internalin family inL. monocytogenes.

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Polarized distribution of Listeria monocytogenes surface protein ActA at the site of directional actin assembly

Journal of Cell Science ◽

10.1242/jcs.105.3.699 ◽

1993 ◽

Vol 105 (3) ◽

pp. 699-710 ◽

Cited By ~ 5

Author(s):

C. Kocks ◽

R. Hellio ◽

P. Gounon ◽

H. Ohayon ◽

P. Cossart

Keyword(s):

Listeria Monocytogenes ◽

Surface Protein ◽

Intracellular Bacteria ◽

Intracellular Pathogen ◽

Actin Assembly ◽

Bacterial Gene ◽

Bacterial Surface ◽

Left Behind ◽

Bacterial Division ◽

Host Tissues

The facultative intracellular pathogen Listeria monocytogenes can infect host tissues by using directional actin assembly to propel itself from one cell into another. The movement is generated by continuous actin assembly from one end of the bacterium into a tail, which is left behind in the cytoplasm. Bacterial actin assembly requires expression of the bacterial gene actA. We have used immunocytochemistry to show that the actA gene product, ActA, is distributed asymmetrically on the bacterial surface: it is not expressed at one pole and is increasingly concentrated towards the other. This polarized distribution of ActA was linked to bacterial division: ActA protein was not, or only faintly, expressed at the pole that had been formed during the previous division. On intracellular bacteria ActA was expressed at the site of actin assembly, suggesting that ActA may be involved in actin filament nucleation off the bacterial surface. We predict that the asymmetrical distribution of this protein is required for the ability of intracellular Listeria to move in the direction of the non-ActA expressing pole.

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Lactoferricin influences early events of Listeria monocytogenes infection in THP-1 human macrophages

Journal of Medical Microbiology ◽

10.1099/jmm.0.05367-0 ◽

2004 ◽

Vol 53 (2) ◽

pp. 87-91 ◽

Cited By ~ 7

Author(s):

Catia Longhi ◽

Maria P. Conte ◽

Michela Penta ◽

Alessia Cossu ◽

Giovanni Antonini ◽

...

Keyword(s):

Listeria Monocytogenes ◽

Temperature Shift ◽

Bactericidal Effect ◽

Significant Inhibition ◽

Host Cells ◽

Bovine Lactoferrin ◽

Antibacterial Effects ◽

Food Borne ◽

Listeria Monocytogenes Infection ◽

Ifn Γ

Bovine lactoferrin (BLf) and its derivative peptide lactoferricin B (LfcinB) are known for their antimicrobial activity towards several pathogens, including Listeria monocytogenes, a food-borne Gram-positive invasive bacterium that infects a wide variety of host cells, including professional phagocytes. To add further information on the antibacterial effects of these compounds, the influence of BLf, LfcinB and the antimicrobial centre of LfcinB, the hexapeptide LfcinB4–9, on the invasive behaviour of L. monocytogenes was analysed in IFN-γ-activated human macrophagic cells (THP-1). Significant inhibition of bacterial entry in THP-1 cells was observed at LfcinB concentrations that were unable to produce any bacteriostatic or bactericidal effect, compared with BLf and LfcinB4–9 peptide. This inhibition occurred when LfcinB was incubated during the bacterial infection step and was not due only to competition for common glycosaminoglycan receptors. Assays performed through a temperature shift from 4 to 37 °C showed that inhibition of invasion took place at an early post-adsorption step, although an effect on a different step of intracellular infection could not be ruled out.

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Loss of Flagellum-Based Motility by Listeria monocytogenes Results in Formation of Hyperbiofilms

Journal of Bacteriology ◽

10.1128/jb.00155-08 ◽

2008 ◽

Vol 190 (17) ◽

pp. 6030-6034 ◽

Cited By ~ 49

Author(s):

Tatsaporn Todhanakasem ◽

Glenn M. Young

Keyword(s):

Listeria Monocytogenes ◽

Biofilm Formation ◽

High Density ◽

Gram Positive ◽

Surface Attachment ◽

Bacterial Surface ◽

Food Borne ◽

Biofilm Development

ABSTRACT Biofilm formation by the gram-positive, motile, food-borne pathogen Listeria monocytogenes was demonstrated to occur by an ordered series of stages. Biofilm development involves flagellum-based motility, which when blocked decreases initial bacterial surface attachment but subsequently leads to the formation of hyperbiofilms, surface-attached communities reaching high density.

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