A novel receptor – ligand pathway for entry of Francisella tularensis in monocyte-like THP-1 cells: interaction between surface nucleolin and bacterial elongation factor Tu

Barel, Monique; Hovanessian, Ara G.; Meibom, Karin L.; Briand, Jean Paul; Dupuis, Marion; Charbit, Alain

doi:10.1186/1471-2180-8-145

Cited by 85 publications

(82 citation statements)

References 53 publications

(86 reference statements)

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“…Several recovered proteins are predicted to be cytoplasmic. While many of these socalled cytoplasmic proteins were recovered in another surface biotinylation and affinity proteomic study of A. phagocytophilum or have homologs in other bacteria that localize to and function on bacterial surfaces (47,(55)(56)(57)(58)(59)(60)(61)(62)(63)(64), it remains to be verified if all recovered proteins in this study are in fact surface localized. Though we initially identified Asp14 on the A. phagocytophilum DC surface, indirect immunofluorescence analyses revealed that the bacterium constitutively expresses Asp14 throughout its development in HL-60, RF/6A, and ISE6 cells.…”

Section: Discussionmentioning

confidence: 85%

“…APH_0240 (the chaperonin GroEL), APH_0346 (DnaK), and APH_1032 (the elongation factor Tu) were chosen because these housekeeping proteins have been shown to moonlight as surface proteins in A. phagocytophilum and other bacteria. Moreover, these proteins have been implicated as adhesins in other bacteria (47,(55)(56)(57)(58)(59)(60)(61)(62)(63)(64). Of the 11 candidates, Omp-1A, Omp85, Msp5, and APH_0441 carry predicted N-terminal signal peptide sequences.…”

Section: Resultsmentioning

confidence: 99%

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Anaplasma phagocytophilum Asp14 Is an Invasin That Interacts with Mammalian Host Cells via Its C Terminus To Facilitate Infection

et al. 2013

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e Anaplasma phagocytophilum, a member of the family Anaplasmataceae, is the tick-transmitted obligate intracellular bacterium that causes human granulocytic anaplasmosis. The life cycle of A. phagocytophilum is biphasic, transitioning between the noninfectious reticulate cell (RC) and infectious dense-cored (DC) forms. We analyzed the bacterium's DC surface proteome by selective biotinylation of surface proteins, NeutrAvidin affinity purification, and mass spectrometry. Transcriptional profiling of selected outer membrane protein candidates over the course of infection revealed that aph_0248 (designated asp14 [14-kDa A. phagocytophilum surface protein]) expression was upregulated the most during A. phagocytophilum cellular invasion. asp14 transcription was induced during transmission feeding of A. phagocytophilum-infected ticks on mice and was upregulated when the bacterium engaged its receptor, P-selectin glycoprotein ligand 1. Asp14 localized to the A. phagocytophilum surface and was expressed during in vivo infection. Treating DC organisms with Asp14 antiserum or preincubating mammalian host cells with glutathione S-transferase (GST)-Asp14 significantly inhibited infection of host cells. Moreover, preincubating host cells with GST-tagged forms of both Asp14 and outer membrane protein A, another A. phagocytophilum invasin, pronouncedly reduced infection relative to treatment with either protein alone. The Asp14 domain that is sufficient for cellular adherence and invasion lies within the C-terminal 12 to 24 amino acids and is conserved among other Anaplasma and Ehrlichia species. These results identify Asp14 as an A. phagocytophilum surface protein that is critical for infection, delineate its invasion domain, and demonstrate the potential of targeting Asp14 in concert with OmpA for protecting against infection by A. phagocytophilum and other Anaplasmataceae pathogens.

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Section: Discussionmentioning

confidence: 85%

Section: Resultsmentioning

confidence: 99%

Anaplasma phagocytophilum Asp14 Is an Invasin That Interacts with Mammalian Host Cells via Its C Terminus To Facilitate Infection

et al. 2013

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“…The scavenger A receptor (SRA), although traditionally known to play a role in uptake of unopsonized bacteria, contributes to the uptake of serum-opsonized Francisella, since SRA Ϫ/Ϫ macrophages exhibit a 20% reduction in the uptake of serumopsonized LVS (176). Macrophage cell surface-exposed nucleolin has also been implicated in uptake of serum-opsonized Francisella by binding the bacterial membrane protein EF-Tu (19). Finally, MR-mediated uptake also plays a role in uptake of serum-opsonized Francisella (roughly 30% decreased uptake when blocked) (90).…”

Section: Mechanisms Of Entry and Fate Of Intracellular Francisellamentioning

confidence: 99%

Subversion of Host Recognition and Defense Systems by Francisella spp

Jones

Napier

Sampson

et al. 2012

Microbiol Mol Biol Rev

123

151

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SUMMARY Francisella tularensis is a Gram-negative intracellular pathogen and the causative agent of the disease tularemia. Inhalation of as few as 10 bacteria is sufficient to cause severe disease, making F. tularensis one of the most highly virulent bacterial pathogens. The initial stage of infection is characterized by the “silent” replication of bacteria in the absence of a significant inflammatory response. Francisella achieves this difficult task using several strategies: (i) strong integrity of the bacterial surface to resist host killing mechanisms and the release of inflammatory bacterial components (pathogen-associated molecular patterns [PAMPs]), (ii) modification of PAMPs to prevent activation of inflammatory pathways, and (iii) active modulation of the host response by escaping the phagosome and directly suppressing inflammatory pathways. We review the specific mechanisms by which Francisella achieves these goals to subvert host defenses and promote pathogenesis, highlighting as-yet-unanswered questions and important areas for future study.

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“…For this reason, many studies have focused on elucidating the Francisella life cycle in this cell type. Receptors that mediate phagocytosis of opsonized and unopsonized bacteria have been described and include complement receptor 3 (CR3) (CD11b/CD18), complement receptor 4 (CR4) (CD11c/ CD18), scavenger receptor A, mannose receptor, and nucleolin (5)(6)(7)(8)(9)(10). Shortly after uptake, both F. tularensis and F. novicida disrupt phagosome maturation so that phagosome-lysosome fusion is impaired and bacteria escape from a late-endosome-like compartment to replicate in the macrophage cytosol (11)(12)(13)(14).…”

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confidence: 99%

Disruption of Francisella tularensis Schu S4 iglI , iglJ , and pdpC Genes Results in Attenuation for Growth in Human Macrophages and In Vivo Virulence in Mice and Reveals a Unique Phenotype for pdpC

et al. 2013

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e Francisella tularensis is a facultative intracellular bacterial pathogen and the causative agent of tularemia. After infection of macrophages, the organism escapes from its phagosome and replicates to high density in the cytosol, but the bacterial factors required for these aspects of virulence are incompletely defined. Here, we describe the isolation and characterization of Francisella tularensis subsp. tularensis strain Schu S4 mutants that lack functional iglI, iglJ, or pdpC, three genes of the Francisella pathogenicity island. Our data demonstrate that these mutants were defective for replication in primary human monocyte-derived macrophages and murine J774 cells yet exhibited two distinct phenotypes. The iglI and iglJ mutants were similar to one another, exhibited profound defects in phagosome escape and intracellular growth, and appeared to be trapped in cathepsin Dpositive phagolysosomes. Conversely, the pdpC mutant avoided trafficking to lysosomes, phagosome escape was diminished but not ablated, and these organisms replicated in a small subset of infected macrophages. The phenotype of each mutant strain was reversed by trans complementation. In vivo virulence was assessed by intranasal infection of BALB/c mice. The mutants appeared avirulent, as all mice survived infection with 10 8 CFU iglJ-or pdpC-deficient bacteria. Nevertheless, the pdpC mutant disseminated to the liver and spleen before being eliminated, whereas the iglJ mutant did not. Taken together, our data demonstrate that the pathogenicity island genes tested are essential for F. tularensis Schu S4 virulence and further suggest that pdpC may play a unique role in this process, as indicated by its distinct intermediate phenotype.

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A novel receptor – ligand pathway for entry of Francisella tularensis in monocyte-like THP-1 cells: interaction between surface nucleolin and bacterial elongation factor Tu

Cited by 85 publications

References 53 publications

Anaplasma phagocytophilum Asp14 Is an Invasin That Interacts with Mammalian Host Cells via Its C Terminus To Facilitate Infection

Anaplasma phagocytophilum Asp14 Is an Invasin That Interacts with Mammalian Host Cells via Its C Terminus To Facilitate Infection

Subversion of Host Recognition and Defense Systems by Francisella spp

Disruption of Francisella tularensis Schu S4 iglI , iglJ , and pdpC Genes Results in Attenuation for Growth in Human Macrophages and In Vivo Virulence in Mice and Reveals a Unique Phenotype for pdpC

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