title: Brucella Intracellular Life Relies on the Transmembrane Protein CD98 Heavy Chain.
abstract: Brucella are intracellular bacterial pathogens that use a type IV secretion system (T4SS) to escape host defenses and create a niche in which they can multiply. Although the importance of Brucella T4SS is clear, little is known about its interactions with host cell structures. In this study, we identified the eukaryotic protein CD98hc as a partner for Brucella T4SS subunit VirB2. This transmembrane glycoprotein is involved in amino acid transport, modulation of integrin signaling, and cell-to-cell fusion. Knockdown of CD98hc expression in HeLa cells demonstrated that it is essential for Brucella infection. Using knockout dermal fibroblasts, we confirmed its role for Brucella but found that it is not required for Salmonella infection. CD98hc transiently accumulates around the bacteria during the early phases of infection and is required for both optimal bacterial uptake and intracellular multiplication of Brucella. These results provide new insights into the complex interplay between Brucella and its host.
authors.affiliation: INSERM, U1047 Université Montpellier 1, UFR de Médecine, Nîmes.
authors.forename: Anne
authors.initials: A
authors.lastname: Keriel
authors.affiliation: INSERM, U1047 Université Montpellier 1, UFR de Médecine, Nîmes.
authors.forename: Eric
authors.initials: E
authors.lastname: Botella
authors.affiliation: INSERM, U1081, CNRS, UMR7284, Institute for Research on Cancer and Aging, University of Nice Sophia Antipolis, France.
authors.forename: Soline
authors.initials: S
authors.lastname: Estrach
authors.affiliation: INSERM, U1047 Université Montpellier 1, UFR de Médecine, Nîmes.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Bragagnolo
authors.affiliation: INSERM, U1047 Université Montpellier 1, UFR de Médecine, Nîmes.
authors.forename: Annette C
authors.initials: AC
authors.lastname: Vergunst
authors.affiliation: INSERM, U1081, CNRS, UMR7284, Institute for Research on Cancer and Aging, University of Nice Sophia Antipolis, France.
authors.forename: Chloe C
authors.initials: CC
authors.lastname: Feral
authors.affiliation: INSERM, U1047 Université Montpellier 1, UFR de Médecine, Nîmes.
authors.forename: David
authors.initials: D
authors.lastname: O'Callaghan
mesh_terms: D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D002002:Brucella / Q000378:metabolism / Q000472:pathogenicity*; D002006:Brucellosis / Q000378:metabolism / Q000382:microbiology; D002478:Cells, Cultured; D005347:Fibroblasts / Q000737:chemistry / Q000378:metabolism / Q000382:microbiology; D027282:Fusion Regulatory Protein 1, Heavy Chain / Q000235:genetics / Q000378:metabolism*; D055786:Gene Knockout Techniques; D006367:HeLa Cells; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000502:physiology*; D006801:Humans; D042541:Intracellular Space / Q000737:chemistry / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D012475:Salmonella; D014617:Vacuoles / Q000378:metabolism / Q000382:microbiology; D037521:Virulence Factors / Q000378:metabolism
chemical_list: D001425:Bacterial Outer Membrane Proteins; D027282:Fusion Regulatory Protein 1, Heavy Chain; D037521:Virulence Factors
keywords: 4F2, SCL2A3, amino-acid transport; Brucella; CD98; T4SS; VirB; fibroblasts; integrin