<i>Listeria monocytogenes</i> remodels the cell surface in the blood‐stage

Quereda, J.J.; Portillo, Francisco García‐del; Pucciarelli, M. Graciela

doi:10.1111/1758-2229.12416

Cited by 15 publications

(11 citation statements)

References 45 publications

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“…We speculate that heme could act as a host-derived signal to induce the expression of LAP in blood-rich environments. So far, LAP has been implicated in the translocation of L. monocytogenes across the intestinal barrier; however, LAP is also highly produced by L. monocytogenes in blood, relative to bacteria grown in rich medium, suggesting that LAP could play a role in the dissemination of L. monocytogenes to deep organs (Quereda et al, 2016). Although cell adhesion studies and mouse bioassays clearly support a major role for LAP during the intestinal phase of infection, a LAP-deficient strain also showed reduced adhesion to Vero kidney cells (Jaradat et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Listeria monocytogenes Relies on the Heme-Regulated Transporter hrtAB to Resist Heme Toxicity and Uses Heme as a Signal to Induce Transcription of lmo1634, Encoding Listeria Adhesion Protein

et al. 2018

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For pathogenic bacteria, host-derived heme represents an important metabolic cofactor and a source for iron. However, high levels of heme are toxic to bacteria. We have previously shown that excess heme has a growth-inhibitory effect on the Gram-positive foodborne pathogen Listeria monocytogenes, and we have learned that the LhrC1-5 family of small RNAs, together with the two-component system (TCS) LisRK, play a role in the adaptation of L. monocytogenes to heme stress conditions. However, a broader knowledge on how this pathogen responds to heme toxicity is still lacking. Here, we analyzed the global transcriptomic response of L. monocytogenes to heme stress. We found that the response of L. monocytogenes to excess heme is multifaceted, involving various strategies acting to minimize the toxic effects of heme. For example, heme exposure triggers the SOS response that deals with DNA damage. In parallel, L. monocytogenes shuts down the transcription of genes involved in heme/iron uptake and utilization. Furthermore, heme stress resulted in a massive increase in the transcription of a putative heme detoxification system, hrtAB, which is highly conserved in Gram-positive bacteria. As expected, we found that the TCS HssRS is required for heme-mediated induction of hrtAB and that a functional heme efflux system is essential for L. monocytogenes to resist heme toxicity. Curiously, the most highly up-regulated gene upon heme stress was lmo1634, encoding the Listeria adhesion protein, LAP, which acts to promote the translocation of L. monocytogenes across the intestinal barrier. Additionally, LAP is predicted to act as a bifunctional acetaldehyde-CoA/alcohol dehydrogenase. Surprisingly, a mutant lacking lmo1634 grows well under heme stress conditions, showing that LAP is not required for L. monocytogenes to resist heme toxicity. Likewise, a functional ResDE TCS, which contributes to heme-mediated expression of lmo1634, is not required for the adaptation of L. monocytogenes to heme stress conditions. Collectively, this study provides novel insights into the strategies employed by L. monocytogenes to resist heme toxicity. Our findings indicate that L. monocytogenes is using heme as a host-derived signaling molecule to control the expression of its virulence genes, as exemplified by lmo1634.

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Section: Discussionmentioning

confidence: 99%

Listeria monocytogenes Relies on the Heme-Regulated Transporter hrtAB to Resist Heme Toxicity and Uses Heme as a Signal to Induce Transcription of lmo1634, Encoding Listeria Adhesion Protein

et al. 2018

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“…Upon ingestion of contaminated food, L. monocytogenes colonizes the intestine and crosses the intestinal barrier, disseminating via the blood to the liver, spleen, brain, and placenta (1, 2). The listeriosis fatality rate is estimated to be 20 to 30% of infected individuals despite antibiotic treatment (1).…”

Section: Introductionmentioning

confidence: 99%

Listeriolysin S Is a Streptolysin S-Like Virulence Factor That Targets Exclusively Prokaryotic CellsIn Vivo

Quereda

Nahori

Meza-Torres

et al. 2017

mBio

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Streptolysin S (SLS)-like virulence factors from clinically relevant Gram-positive pathogens have been proposed to behave as potent cytotoxins, playing key roles in tissue infection. Listeriolysin S (LLS) is an SLS-like hemolysin/bacteriocin present among Listeria monocytogenes strains responsible for human listeriosis outbreaks. As LLS cytotoxic activity has been associated with virulence, we investigated the LLS-specific contribution to host tissue infection. Surprisingly, we first show that LLS causes only weak red blood cell (RBC) hemolysis in vitro and neither confers resistance to phagocytic killing nor favors survival of L. monocytogenes within the blood cells or in the extracellular space (in the plasma). We reveal that LLS does not elicit specific immune responses, is not cytotoxic for eukaryotic cells, and does not impact cell infection by L. monocytogenes. Using in vitro cell infection systems and a murine intravenous infection model, we actually demonstrate that LLS expression is undetectable during infection of cells and murine inner organs. Importantly, upon intravenous animal inoculation, L. monocytogenes is found in the gastrointestinal system, and only in this environment LLS expression is detected in vivo. Finally, we confirm that LLS production is associated with destruction of target bacteria. Our results demonstrate therefore that LLS does not contribute to L. monocytogenes tissue injury and virulence in inner host organs as previously reported. Moreover, we describe that LlsB, a putative posttranslational modification enzyme encoded in the LLS operon, is necessary for murine inner organ colonization. Overall, we demonstrate that LLS is the first SLS-like virulence factor targeting exclusively prokaryotic cells during in vivo infections.

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“…In the present study, the panning strategies using cell wall, membrane, and cytoplasm were all able to provide binders against PDC-E2, corroborating the assumption of its location in different cellular parts. Further studies could address whether other metabolic proteins that show up on the bacterial surface provide useful biomarkers for detection, especially considering that Listeria surface is remodeled according to the environment 63 .…”

Section: Discussionmentioning

confidence: 99%

Pyruvate dehydrogenase complex—enzyme 2, a new target for Listeria spp. detection identified using combined phage display technologies

Moreira

Köllner

Helmsing

et al. 2020

Sci Rep

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The genus Listeria comprises ubiquitous bacteria, commonly present in foods and food production facilities. In this study, three different phage display technologies were employed to discover targets, and to generate and characterize novel antibodies against Listeria: antibody display for biomarker discovery and antibody generation; ORFeome display for target identification; and single-gene display for epitope characterization. With this approach, pyruvate dehydrogenase complex—enzyme 2 (PDC-E2) was defined as a new detection target for Listeria, as confirmed by immunomagnetic separation-mass spectrometry (IMS-MS). Immunoblot and fluorescence microscopy showed that this protein is accessible on the bacterial cell surface of living cells. Recombinant PDC-E2 was produced in E. coli and used to generate 16 additional antibodies. The resulting set of 20 monoclonal scFv-Fc was tested in indirect ELISA against 17 Listeria and 16 non-Listeria species. Two of them provided 100% sensitivity (CI 82.35–100.0%) and specificity (CI 78.20–100.0%), confirming PDC-E2 as a suitable target for the detection of Listeria. The binding region of 18 of these antibodies was analyzed, revealing that ≈ 90% (16/18) bind to the lipoyl domains (LD) of the target. The novel target PDC-E2 and highly specific antibodies against it offer new opportunities to improve the detection of Listeria.

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Listeria monocytogenes remodels the cell surface in the blood‐stage

Cited by 15 publications

References 45 publications

Listeria monocytogenes Relies on the Heme-Regulated Transporter hrtAB to Resist Heme Toxicity and Uses Heme as a Signal to Induce Transcription of lmo1634, Encoding Listeria Adhesion Protein

Listeria monocytogenes Relies on the Heme-Regulated Transporter hrtAB to Resist Heme Toxicity and Uses Heme as a Signal to Induce Transcription of lmo1634, Encoding Listeria Adhesion Protein

Listeriolysin S Is a Streptolysin S-Like Virulence Factor That Targets Exclusively Prokaryotic CellsIn Vivo

Pyruvate dehydrogenase complex—enzyme 2, a new target for Listeria spp. detection identified using combined phage display technologies

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