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Even though microorganisms show a wide repertoire of strategies to subvert the activity of actin, most of them converge in the ones that activate nucleating factors, such as the Arp2\/3 complex.\n                      <jats:italic>Brucella<\/jats:italic>\n                      spp. are intracellular pathogens capable of establishing chronic infections in their hosts. The ability to subvert the host cell response is dependent on the capacity of the bacterium to attach, invade, avoid degradation in the phagocytic compartment, replicate in an endoplasmic reticulum-derived compartment and egress. Even though a significant number of mechanisms deployed by\n                      <jats:italic>Brucella<\/jats:italic>\n                      in these different phases have been identified and characterized, none of them have been described to target actin as a cellular component. In this manuscript, we describe the identification of a novel virulence factor (NpeA) that promotes niche formation. NpeA harbors a short linear motif (SLiM) present within an amphipathic alpha helix that has been described to bind the GTPase-binding domain (GBD) of N-WASP and stabilizes the autoinhibited state. Our results show that NpeA is secreted in a Type IV secretion system-dependent manner and that deletion of the gene diminishes the intracellular replication capacity of the bacterium.\n                      <jats:italic>In vitro<\/jats:italic>\n                      and\n                      <jats:italic>ex vivo<\/jats:italic>\n                      experiments demonstrate that NpeA binds N-WASP and that the short linear motif is required for the biological activity of the protein.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        The modulation of actin-binding effectors that regulate the activity of this fundamental cellular protein is a common theme among bacterial pathogens. The neural Wiskott\u2013Aldrich syndrome protein (N-WASP) is a protein that several pathogens target to hijack actin dynamics. The highly adapted intracellular bacterium\n                        <jats:italic>Brucella<\/jats:italic>\n                        has evolved a wide repertoire of virulence factors that modulate many activities of the host cell to establish successful intracellular replication niches, but, to date, no effector proteins have been implicated in the modulation of actin dynamics. We present here the identification of a virulence factor that harbors a short linear motif (SLiM) present within an amphipathic alpha helix that has been described to bind the GTPase-binding domain (GBD) of N-WASP stabilizing its autoinhibited state. We demonstrate that this protein is a Type IV secretion effector that targets N-WASP-promoting intracellular survival and niche formation.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.00726-24","type":"journal-article","created":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T09:01:35Z","timestamp":1717750895000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":11,"title":["<i>Brucella<\/i>\n                    NpeA is a secreted Type IV effector containing an N-WASP-binding short linear motif that promotes niche formation"],"prefix":"10.1128","volume":"15","author":[{"given":"Agostina","family":"Gim\u00e9nez","sequence":"first","affiliation":[{"name":"Instituto de Investigaciones Biotecnol\u00f3gicas, Universidad Nacional de San Mart\u00edn (UNSAM)-Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Escuela de Bio y Nanotecnolog\u00edas (EByN), Universidad Nacional de San Mart\u00edn, San Mart\u00edn, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariela G.","family":"Del Giudice","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biotecnol\u00f3gicas, Universidad Nacional de San Mart\u00edn (UNSAM)-Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Escuela de Bio y Nanotecnolog\u00edas (EByN), Universidad Nacional de San Mart\u00edn, San Mart\u00edn, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula V.","family":"L\u00f3pez","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biotecnol\u00f3gicas, Universidad Nacional de San Mart\u00edn (UNSAM)-Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Escuela de Bio y Nanotecnolog\u00edas (EByN), Universidad Nacional de San Mart\u00edn, San Mart\u00edn, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Guaimas","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biotecnol\u00f3gicas, Universidad Nacional de San Mart\u00edn (UNSAM)-Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Escuela de Bio y Nanotecnolog\u00edas (EByN), Universidad Nacional de San Mart\u00edn, San Mart\u00edn, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo","family":"S\u00e1mano-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Zhejiang University School of Medicine, International Campus, Zhejiang University, Haining, China"},{"name":"Biomedical Sciences, Edinburgh Medical School, The University of Edinburgh, Edinburgh, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toby J.","family":"Gibson","sequence":"additional","affiliation":[{"name":"Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc\u00eda B.","family":"Chemes","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biotecnol\u00f3gicas, Universidad Nacional de San Mart\u00edn (UNSAM)-Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Escuela de Bio y Nanotecnolog\u00edas (EByN), Universidad Nacional de San Mart\u00edn, San Mart\u00edn, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos O.","family":"Arregui","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biotecnol\u00f3gicas, Universidad Nacional de San Mart\u00edn (UNSAM)-Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Escuela de Bio y Nanotecnolog\u00edas (EByN), Universidad Nacional de San Mart\u00edn, San Mart\u00edn, Buenos Aires, 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