scholarly journals Listeria monocytogenes Exploits Normal Host Cell Processes to Spread from Cell to Cell✪

1999 ◽  
Vol 146 (6) ◽  
pp. 1333-1350 ◽  
Author(s):  
Jennifer R. Robbins ◽  
Angela I. Barth ◽  
Hélène Marquis ◽  
Eugenio L. de Hostos ◽  
W. James Nelson ◽  
...  
Keyword(s):  
Listeria Monocytogenes ◽  
Host Cell ◽  
Mdck Cells ◽  
Recipient Cell ◽  
Cell Monolayer ◽  
Bacterial Pathogen ◽  
Host Cells ◽  
Turnover Rates ◽  
Membrane Bound ◽  
Intercellular Spread

The bacterial pathogen, Listeria monocytogenes, grows in the cytoplasm of host cells and spreads intercellularly using a form of actin-based motility mediated by the bacterial protein ActA. Tightly adherent monolayers of MDCK cells that constitutively express GFP-actin were infected with L. monocytogenes, and intercellular spread of bacteria was observed by video microscopy. The probability of formation of membrane-bound protrusions containing bacteria decreased with host cell monolayer age and the establishment of extensive cell-cell contacts. After their extension into a recipient cell, intercellular membrane-bound protrusions underwent a period of bacterium-dependent fitful movement, followed by their collapse into a vacuole and rapid vacuolar lysis. Actin filaments in protrusions exhibited decreased turnover rates compared with bacterially associated cytoplasmic actin comet tails. Recovery of motility in the recipient cell required 1–2 bacterial generations. This delay may be explained by acid-dependent cleavage of ActA by the bacterial metalloprotease, Mpl. Importantly, we have observed that low levels of endocytosis of neighboring MDCK cell surface fragments occurs in the absence of bacteria, implying that intercellular spread of bacteria may exploit an endogenous process of paracytophagy.

scholarly journals Invasion of the Brain by Listeria monocytogenes Is Mediated by InlF and Host Cell Vimentin

mBio ◽  
2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Pallab Ghosh ◽  
Elizabeth M. Halvorsen ◽  
Dustin A. Ammendolia ◽  
Nirit Mor-Vaknin ◽  
Mary X. D. O’Riordan ◽  
...  
Keyword(s):  
Listeria Monocytogenes ◽  
Host Cell ◽  
Bacterial Pathogen ◽  
Surface Protein ◽  
Host Cells ◽  
Intermediate Filament Protein ◽  
Life Threatening ◽  
Host Cell Surface ◽  
Filament Protein ◽  
The Brain

ABSTRACTListeria monocytogenesis a facultative intracellular bacterial pathogen that is frequently associated with food-borne infection. Of particular concern is the ability ofL. monocytogenesto breach the blood-brain barrier, leading to life-threatening meningitis and encephalitis. The mechanisms used by bacterial pathogens to infect the brain are not fully understood. Here we show thatL. monocytogenesis able to utilize vimentin for invasion of host cells. Vimentin is a type III intermediate filament protein within the cytosol but is also expressed on the host cell surface. We found thatL. monocytogenesinteraction with surface-localized vimentin promoted bacterial uptake. Furthermore, in the absence of vimentin,L. monocytogenescolonization of the brain was severely compromised in mice. TheL. monocytogenesvirulence factor InlF was found to bind vimentin and was necessary for optimal bacterial colonization of the brain. These studies reveal a novel receptor-ligand interaction that enhances infection of the brain byL. monocytogenesand highlights the importance of surface vimentin in host-pathogen interactions.IMPORTANCEListeria monocytogenesis an intracellular bacterial pathogen that is capable of invading numerous host cells during infection.L. monocytogenescan cross the blood-brain barrier, leading to life-threatening meningitis. Here we show that anL. monocytogenessurface protein, InlF, is necessary for optimal colonization of the brain in mice. Furthermore, in the absence of vimentin, a cytosolic intermediate filament protein that is also present on the surface of brain endothelial cells, colonization of the brain was significantly impaired. We further show that InlF binds vimentin to mediate invasion of host cells. This work identifies InlF as a bacterial surface protein with specific relevance for infection of the brain and underscores the significance of host cell surface vimentin interactions in microbial pathogenesis.

scholarly journals The Listeria monocytogenes hemolysin has an acidic pH optimum to compartmentalize activity and prevent damage to infected host cells

2002 ◽  
Vol 156 (6) ◽  
pp. 1029-1038 ◽  
Author(s):  
Ian J. Glomski ◽  
Margaret M. Gedde ◽  
Albert W. Tsang ◽  
Joel A. Swanson ◽  
Daniel A. Portnoy
Keyword(s):  
Listeria Monocytogenes ◽  
Bacterial Pathogen ◽  
Cytolytic Activity ◽  
Host Cells ◽  
Adaptive Mutation ◽  
Acidic Ph ◽  
Listeriolysin O ◽  
Lysosomal Hydrolases ◽  
Ph Optimum ◽  
Neutral Ph

Listeria monocytogenes is a facultative intracellular bacterial pathogen that escapes from a phagosome and grows in the host cell cytosol. The pore-forming cholesterol-dependent cytolysin, listeriolysin O (LLO), mediates bacterial escape from vesicles and is ∼10-fold more active at an acidic than neutral pH. By swapping dissimilar residues from a pH-insensitive orthologue, perfringolysin O (PFO), we identified leucine 461 as unique to pathogenic Listeria and responsible for the acidic pH optimum of LLO. Conversion of leucine 461 to the threonine present in PFO increased the hemolytic activity of LLO almost 10-fold at a neutral pH. L. monocytogenes synthesizing LLO L461T, expressed from its endogenous site on the bacterial chromosome, resulted in a 100-fold virulence defect in the mouse listeriosis model. These bacteria escaped from acidic phagosomes and initially grew normally in cells and spread cell to cell, but prematurely permeabilized the host membrane and killed the cell. These data show that the acidic pH optimum of LLO results from an adaptive mutation that acts to limit cytolytic activity to acidic vesicles and prevent damage in the host cytosol, a strategy also used by host cells to compartmentalize lysosomal hydrolases.

scholarly journals Perforin-2 Protects Host Cells and Mice by Restricting the Vacuole to Cytosol Transitioning of a Bacterial Pathogen

2016 ◽  
Vol 84 (4) ◽  
pp. 1083-1091 ◽  
Author(s):  
Ryan McCormack ◽  
Wael Bahnan ◽  
Niraj Shrestha ◽  
Justin Boucher ◽  
Marcella Barreto ◽  
...  
Keyword(s):  
Bacterial Pathogen ◽  
Virulence Gene ◽  
Systemic Infection ◽  
Protective Role ◽  
Host Cells ◽  
Content Type ◽  
Virulence Gene Expression ◽  
Membrane Bound ◽  
High Level ◽  
Macpf Domain

The host-encoded Perforin-2 (encoded by the macrophage-expressed gene 1,Mpeg1), which possesses a pore-forming MACPF domain, reduces the viability of bacterial pathogens that reside within membrane-bound compartments. Here, it is shown that Perforin-2 also restricts the proliferation of the intracytosolic pathogenListeria monocytogenes. Within a few hours of systemic infection, the massive proliferation ofL. monocytogenesinPerforin-2−/−mice leads to a rapid appearance of acute disease symptoms. We go on to show in culturedPerforin-2−/−cells that the vacuole-to-cytosol transitioning ofL. monocytogenesis greatly accelerated. Unexpectedly, we found that inPerforin-2−/−macrophages,Listeria-containing vacuoles quickly (≤15 min) acidify, and that this was coincident with greater virulence gene expression, likely accounting for the more rapid translocation ofL. monocytogenesto its replicative niche in the cytosol. This hypothesis was supported by our finding that aL. monocytogenesstrain expressing virulence factors at a constitutively high level replicated equally well inPerforin-2+/+andPerforin-2−/−macrophages. Our findings suggest that the protective role of Perforin-2 against listeriosis is based on it limiting the intracellular replication of the pathogen. This cellular activity of Perforin-2 may derive from it regulating the acidification ofListeria-containing vacuoles, thereby depriving the pathogen of favorable intracellular conditions that promote its virulence gene activity.

scholarly journals Mycobacterium tuberculosis infection of host cells in space and time

2019 ◽  
Vol 43 (4) ◽  
pp. 341-361 ◽  
Author(s):  
Claudio Bussi ◽  
Maximiliano G Gutierrez
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Host Cell ◽  
Cell Biology ◽  
Current Knowledge ◽  
Bacterial Pathogen ◽  
Infectious Agent ◽  
Host Cells ◽  
Cellular Mechanisms ◽  
Mycobacterium Tuberculosis Infection ◽  
Human Host

ABSTRACTTuberculosis (TB) caused by the bacterial pathogen Mycobacterium tuberculosis (Mtb) remains one of the deadliest infectious diseases with over a billion deaths in the past 200 years (Paulson 2013). TB causes more deaths worldwide than any other single infectious agent, with 10.4 million new cases and close to 1.7 million deaths in 2017. The obstacles that make TB hard to treat and eradicate are intrinsically linked to the intracellular lifestyle of Mtb. Mtb needs to replicate within human cells to disseminate to other individuals and cause disease. However, we still do not completely understand how Mtb manages to survive within eukaryotic cells and why some cells are able to eradicate this lethal pathogen. Here, we summarise the current knowledge of the complex host cell-pathogen interactions in TB and review the cellular mechanisms operating at the interface between Mtb and the human host cell, highlighting the technical and methodological challenges to investigating the cell biology of human host cell-Mtb interactions.

scholarly journals Pathogenic Biohacking: Induction, Modulation and Subversion of Host Transcriptional Responses by Listeria monocytogenes

Toxins ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 294
Author(s):  
Matthew J. G. Eldridge ◽  
Pascale Cossart ◽  
Mélanie A. Hamon
Keyword(s):  
Gene Expression ◽  
Listeria Monocytogenes ◽  
Virulence Factors ◽  
Bacterial Pathogen ◽  
Typical Feature ◽  
Host Gene ◽  
Host Cells ◽  
Host Gene Expression ◽  
Transcriptional Responses ◽  
The Impact

During infection, the foodborne bacterial pathogen Listeria monocytogenes dynamically influences the gene expression profile of host cells. Infection-induced transcriptional changes are a typical feature of the host-response to bacteria and contribute to the activation of protective genes such as inflammatory cytokines. However, by using specialized virulence factors, bacterial pathogens can target signaling pathways, transcription factors, and epigenetic mechanisms to alter host gene expression, thereby reprogramming the response to infection. Therefore, the transcriptional profile that is established in the host is delicately balanced between antibacterial responses and pathogenesis, where any change in host gene expression might significantly influence the outcome of infection. In this review, we discuss the known transcriptional and epigenetic processes that are engaged during Listeria monocytogenes infection, the virulence factors that can remodel them, and the impact these processes have on the outcome of infection.

scholarly journals Intracellular Gene Expression Profile of Listeria monocytogenes

2006 ◽  
Vol 74 (2) ◽  
pp. 1323-1338 ◽  
Author(s):  
Som Subhra Chatterjee ◽  
Hamid Hossain ◽  
Sonja Otten ◽  
Carsten Kuenne ◽  
Katja Kuchmina ◽  
...  
Keyword(s):  
Gene Expression ◽  
Listeria Monocytogenes ◽  
Host Cell ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Intracellular Survival ◽  
Host Cells ◽  
Wall Structure ◽  
Glucose Limitation ◽  
Serotype 4B

ABSTRACT Listeria monocytogenes is a gram-positive, food-borne microorganism responsible for invasive infections with a high overall mortality. L. monocytogenes is among the very few microorganisms that can induce uptake into the host cell and subsequently enter the host cell cytosol by breaching the vacuolar membrane. We infected the murine macrophage cell line P388D1 with L. monocytogenes strain EGD-e and examined the gene expression profile of L. monocytogenes inside the vacuolar and cytosolic environments of the host cell by using whole-genome microarray and mutant analyses. We found that ∼17% of the total genome was mobilized to enable adaptation for intracellular growth. Intracellularly expressed genes showed responses typical of glucose limitation within bacteria, with a decrease in the amount of mRNA encoding enzymes in the central metabolism and a temporal induction of genes involved in alternative-carbon-source utilization pathways and their regulation. Adaptive intracellular gene expression involved genes that are associated with virulence, the general stress response, cell division, and changes in cell wall structure and included many genes with unknown functions. A total of 41 genes were species specific, being absent from the genome of the nonpathogenic Listeria innocua CLIP 11262 strain. We also detected 25 genes that were strain specific, i.e., absent from the genome of the previously sequenced L. monocytogenes F2365 serotype 4b strain, suggesting heterogeneity in the gene pool required for intracellular survival of L. monocytogenes in host cells. Overall, our study provides crucial insights into the strategy of intracellular survival and measures taken by L. monocytogenes to escape the host cell responses.

scholarly journals Compartmentalization of the Broad-Range Phospholipase C Activity to the Spreading Vacuole Is Critical for Listeria monocytogenes Virulence

2006 ◽  
Vol 75 (1) ◽  
pp. 44-51 ◽  
Author(s):  
P. S. Marie Yeung ◽  
Yoojin Na ◽  
Amanda J. Kreuder ◽  
Hélène Marquis
Keyword(s):  
Listeria Monocytogenes ◽  
Phospholipase C ◽  
Membrane Damage ◽  
Bacterial Pathogen ◽  
Host Cells ◽  
Virulence Attenuation ◽  
Infected Cells ◽  
Host Cell Membranes ◽  
Cell Spread

ABSTRACT Listeria monocytogenes is a bacterial pathogen that multiplies in the cytosol of host cells and spreads directly from cell to cell by using an actin-based mechanism of motility. The broad-range phospholipase C (PC-PLC) of L. monocytogenes contributes to bacterial escape from vacuoles formed upon cell-to-cell spread. PC-PLC is made as an inactive proenzyme whose activation requires cleavage of an N-terminal propeptide. During infection, PC-PLC is activated specifically in acidified vacuoles. To assess the importance of compartmentalizing PC-PLC activity during infection, we created a mutant that makes constitutively active PC-PLC (the plcBΔpro mutant). Results from intracellular growth and cell-to-cell spread assays showed that the plcBΔpro mutant was sensitive to gentamicin, suggesting that unregulated PC-PLC activity causes damage to host cell membranes. This was confirmed by the observation of a twofold increase in staining of live infected cells by a non-membrane-permeant DNA fluorescent dye. However, membrane damage was not sufficient to cause cell lysis and was dependent on bacterial cell-to-cell spread, suggesting that damage was localized to bacterium-containing filopodia. Using an in vivo competitive infection assay, we observed that the plcBΔpro mutant was outcompeted up to 200-fold by the wild-type strain in BALB/c mice. Virulence attenuation was greater when mice were infected orally than when they were infected intravenously, presumably because the plcBΔpro mutant was initially outcompeted in the intestines, reducing the number of mutant bacteria reaching the liver and spleen. Together, these results emphasize the importance for L. monocytogenes virulence of compartmentalizing the activity of PC-PLC during infection.

scholarly journals A non-catalytic histidine residue influences the function of the metalloprotease of Listeria monocytogenes

Microbiology ◽  
2014 ◽  
Vol 160 (1) ◽  
pp. 142-148 ◽  
Author(s):  
Brian M. Forster ◽  
Alan Pavinski Bitar ◽  
Hélène Marquis
Keyword(s):  
Cell Wall ◽  
Listeria Monocytogenes ◽  
Amino Acid ◽  
Positive Charge ◽  
Bacterial Pathogen ◽  
Histidine Residue ◽  
Amino Acid Residues ◽  
Intracellular Growth ◽  
N Terminus ◽  
Membrane Bound

Mpl, a thermolysin-like metalloprotease, and PC-PLC, a phospholipase C, are synthesized as proenzymes by the intracellular bacterial pathogen Listeria monocytogenes. During intracellular growth, L. monocytogenes is temporarily confined in a membrane-bound vacuole whose acidification leads to Mpl autolysis and Mpl-mediated cleavage of the PC-PLC N-terminal propeptide. Mpl maturation also leads to the secretion of both Mpl and PC-PLC across the bacterial cell wall. Previously, we identified negatively charged and uncharged amino acid residues within the N terminus of the PC-PLC propeptide that influence the ability of Mpl to mediate the maturation of PC-PLC, suggesting that these residues promote the interaction of the PC-PLC propeptide with Mpl. In the present study, we identified a non-catalytic histidine residue (H226) that influences Mpl secretion across the cell wall and its ability to process PC-PLC. Our results suggest that a positive charge at position 226 is required for Mpl functions other than autolysis. Based on the charge requirement at this position, we hypothesize that this residue contributes to the interaction of Mpl with the PC-PLC propeptide.

scholarly journals Listeria monocytogenes: The Impact of Cell Death on Infection and Immunity

Pathogens ◽  
2018 ◽  
Vol 7 (1) ◽  
pp. 8 ◽  
Author(s):  
Courtney McDougal ◽  
John-Demian Sauer
Keyword(s):  
Cell Death ◽  
Listeria Monocytogenes ◽  
Host Cell ◽  
Acute Infection ◽  
Host Cells ◽  
Cell Mediated Immunity ◽  
Cell Death Pathways ◽  
Host Cell Death ◽  
The Impact

Listeria monocytogenes has evolved exquisite mechanisms for invading host cells and spreading from cell-to-cell to ensure maintenance of its intracellular lifecycle. As such, it is not surprising that loss of the intracellular replication niche through induction of host cell death has significant implications on the development of disease and the subsequent immune response. Although L. monocytogenes can activate multiple pathways of host cell death, including necrosis, apoptosis, and pyroptosis, like most intracellular pathogens L. monocytogenes has evolved a series of adaptations that minimize host cell death to promote its virulence. Understanding how L. monocytogenes modulates cell death during infection could lead to novel therapeutic approaches. In addition, as L. monocytogenes is currently being developed as a tumor immunotherapy platform, understanding how cell death pathways influence the priming and quality of cell-mediated immunity is critical. This review will focus on the mechanisms by which L. monocytogenes modulates cell death, as well as the implications of cell death on acute infection and the generation of adaptive immunity.

scholarly journals Comprehensive Single Cell Analyses of the Nutritional Environment of Intracellular Salmonella enterica

2021 ◽  
Vol 11 ◽  
Author(s):  
Jennifer Röder ◽  
Pascal Felgner ◽  
Michael Hensel
Keyword(s):  
Host Cell ◽  
Salmonella Enterica ◽  
Nutrient Supply ◽  
Host Cells ◽  
Direct Access ◽  
Uptake System ◽  
Bacterial Proliferation ◽  
Membrane Compartments ◽  
Membrane Bound ◽  
Nutritional Environment

The facultative intracellular pathogen Salmonella enterica Typhimurium (STM) resides in a specific membrane-bound compartment termed the Salmonella-containing vacuole (SCV). STM is able to obtain all nutrients required for rapid proliferation, although being separated from direct access to host cell metabolites. The formation of specific tubular membrane compartments, called Salmonella-induced filaments (SIFs) are known to provides bacterial nutrition by giving STM access to endocytosed material and enabling proliferation. Additionally, STM expresses a range of nutrient uptake system for growth in nutrient limited environments to overcome the nutrition depletion inside the host. By utilizing dual fluorescence reporters, we shed light on the nutritional environment of intracellular STM in various host cells and distinct intracellular niches. We showed that STM uses nutrients of the host cell and adapts uniquely to the different nutrient conditions. In addition, we provide further evidence for improved nutrient supply by SIF formation or presence in the cytosol of epithelial cells, and the correlation of nutrient supply to bacterial proliferation.

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