{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:39:10Z","timestamp":1787503150165,"version":"build-2736575974"},"reference-count":54,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T00:00:00Z","timestamp":1616025600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science KAKENHI","doi-asserted-by":"crossref","award":["15K08470"],"award-info":[{"award-number":["15K08470"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science KAKENHI","doi-asserted-by":"crossref","award":["19K07543"],"award-info":[{"award-number":["19K07543"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science KAKENHI","doi-asserted-by":"crossref","award":["25293106"],"award-info":[{"award-number":["25293106"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science KAKENHI","doi-asserted-by":"crossref","award":["18K07119"],"award-info":[{"award-number":["18K07119"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Kitasato University Research Grant for Young Researchers","award":["2012"],"award-info":[{"award-number":["2012"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    Nuclear factor-kappa B (NF-\u03baB) plays a critical role in the host defense against microbial pathogens. Many pathogens modulate NF-\u03baB signaling to establish infection in their host.\n                    <jats:italic>Salmonella enterica<\/jats:italic>\n                    serovar Typhimurium (\n                    <jats:italic>S<\/jats:italic>\n                    . Typhimurium) possesses two type III secretion systems (T3SS-1 and T3SS-2) and directly injects many effector proteins into host cells. It has been reported that some effectors block NF-\u03baB signaling, but the molecular mechanism of the inactivation of NF-\u03baB signaling in\n                    <jats:italic>S<\/jats:italic>\n                    . Typhimurium is poorly understood. Here, we identified seven type III effectors\u2014GogA, GtgA, PipA, SseK1, SseK2, SseK3, and SteE\u2014that inhibited NF-\u03baB activation in HeLa cells stimulated with TNF-\u03b1. We also determined that only GogA and GtgA are involved in regulation of the activation of NF-\u03baB in HeLa cells infected with\n                    <jats:italic>S<\/jats:italic>\n                    . Typhimurium. GogA, GtgA, and PipA are highly homologous to one another and have the consensus zinc metalloprotease HEXXH motif. Our experiments demonstrated that GogA, GtgA, and PipA each directly cleaved NF-\u03baB p65, whereas GogA and GtgA, but not PipA, inhibited the NF-\u03baB activation in HeLa cells infected with\n                    <jats:italic>S<\/jats:italic>\n                    . Typhimurium. Further, expressions of the\n                    <jats:italic>gogA<\/jats:italic>\n                    or\n                    <jats:italic>gtgA<\/jats:italic>\n                    gene were induced under the SPI-1-and SPI-2-inducing conditions, but expression of the\n                    <jats:italic>pipA<\/jats:italic>\n                    gene was induced only under the SPI-2-inducing condition. We also showed that PipA was secreted into RAW264.7 cells through T3SS-2. Finally, we indicated that PipA elicits bacterial dissemination in the systemic stage of infection of\n                    <jats:italic>S<\/jats:italic>\n                    . Typhimurium via a T3SS-1-independent mechanism. Collectively, our results suggest that PipA, GogA and GtgA contribute to\n                    <jats:italic>S<\/jats:italic>\n                    . Typhimurium pathogenesis in different ways.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0248975","type":"journal-article","created":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T14:03:10Z","timestamp":1616076190000},"page":"e0248975","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":19,"title":["A Salmonella type III effector, PipA, works in a different manner than the PipA family effectors GogA and GtgA"],"prefix":"10.1371","volume":"16","author":[{"given":"Momo","family":"Takemura","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7506-4530","authenticated-orcid":true,"given":"Takeshi","family":"Haneda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hikari","family":"Idei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuyoshi","family":"Miki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhiko","family":"Okada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,3,18]]},"reference":[{"key":"pone.0248975.ref001","first-page":"203","article-title":"NF-\u03baB, the first quarter-century: remarkable progress and outstanding questions","volume":"26","author":"MS Hayden","year":"2012","journal-title":"Genes Dev. 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Cold Spring Harbor Lab"},{"key":"pone.0248975.ref003","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/nrmicro2539","article-title":"Modulation of NF-\u03baB signalling by microbial pathogens","volume":"9","author":"MM Rahman","year":"2011","journal-title":"Nat Rev Microbiol"},{"key":"pone.0248975.ref004","doi-asserted-by":"crossref","first-page":"2839","DOI":"10.1111\/j.1462-5822.2007.01000.x","article-title":"SopD acts cooperatively with SopB during Salmonella enterica serovar Typhimurium invasion","volume":"9","author":"MA Bakowski","year":"2007","journal-title":"Cell Microbiol"},{"key":"pone.0248975.ref005","first-page":"2","article-title":"A Salmonella Virulence Factor Activates the NOD1\/NOD2 Signaling Pathway","author":"A Marijke Keestra","year":"2011","journal-title":"mBio"},{"key":"pone.0248975.ref006","doi-asserted-by":"crossref","first-page":"3843","DOI":"10.1128\/IAI.70.7.3843-3855.2002","article-title":"The Salmonella enterica serotype Typhimurium effector proteins SipA, SopA, SopB, SopD, and SopE2 act in concert to Induce diarrhea in calves","volume":"70","author":"S Zhang","year":"2002","journal-title":"Infect Immun"},{"key":"pone.0248975.ref007","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1128\/IAI.73.1.146-154.2005","article-title":"SipA, SopA, SopB, SopD, and SopE2 contribute to Salmonella enterica serotype Typhimurium invasion of epithelial cells","volume":"73","author":"M Raffatellu","year":"2005","journal-title":"Infect Immun"},{"key":"pone.0248975.ref008","doi-asserted-by":"crossref","first-page":"5045","DOI":"10.4049\/jimmunol.180.7.5045","article-title":"Salmonella secreted factor L deubiquitinase of Salmonella typhimurium inhibits NF-kappaB, suppresses IkappaBalpha ubiquitination and modulates innate immune responses","volume":"180","author":"G Le Negrate","year":"2008","journal-title":"The Journal of 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Microbiol"},{"key":"pone.0248975.ref018","doi-asserted-by":"crossref","first-page":"e1005653","DOI":"10.1371\/journal.ppat.1005653","article-title":"Inhibition of Nuclear transport of NF-\u0138B p65 by the Salmonella type III secretion system effector SpvD","volume":"12","author":"N Rolhion","year":"2016","journal-title":"PLoS Pathog. 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BioMed Central"},{"key":"pone.0248975.ref028","doi-asserted-by":"crossref","first-page":"49804","DOI":"10.1074\/jbc.M404299200","article-title":"Expression and secretion of Salmonella pathogenicity island-2 virulence genes in response to acidification exhibit differential requirements of a functional type III secretion apparatus and SsaL","volume":"279","author":"BK Coombes","year":"2004","journal-title":"J Biol Chem"},{"key":"pone.0248975.ref029","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1128\/IAI.00684-07","article-title":"The NleE\/OspZ family of effector proteins is required for polymorphonuclear transepithelial migration, a characteristic shared by enteropathogenic Escherichia coli and Shigella flexneri infections","volume":"76","author":"DV Zurawski","year":"2008","journal-title":"Infect Immun"},{"key":"pone.0248975.ref030","doi-asserted-by":"crossref","first-page":"e1000898","DOI":"10.1371\/journal.ppat.1000898","article-title":"The type III effectors NleE and NleB from enteropathogenic E. coli and OspZ from Shigella block nuclear translocation of NF-kappaB p65","volume":"6","author":"HJ Newton","year":"2010","journal-title":"PLoS Pathog"},{"key":"pone.0248975.ref031","doi-asserted-by":"crossref","first-page":"e1000743","DOI":"10.1371\/journal.ppat.1000743","article-title":"The type III secretion effector NleE inhibits NF-kappaB activation","volume":"6","author":"C Nadler","year":"2010","journal-title":"PLoS Pathog"},{"key":"pone.0248975.ref032","doi-asserted-by":"crossref","first-page":"5115","DOI":"10.1128\/IAI.72.9.5115-5125.2004","article-title":"SseK1 and SseK2 are novel translocated proteins of Salmonella enterica serovar Typhimurium","volume":"72","author":"SL Kujat Choy","year":"2004","journal-title":"Infect Immun"},{"key":"pone.0248975.ref033","doi-asserted-by":"crossref","first-page":"e17824","DOI":"10.1371\/journal.pone.0017824","article-title":"Salmonella phage ST64B encodes a member of the SseK\/NleB effector family","volume":"6","author":"NF Brown","year":"2011","journal-title":"PLoS ONE"},{"key":"pone.0248975.ref034","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1038\/nature12436","article-title":"Pathogen blocks host death receptor signalling by arginine GlcNAcylation of death domains","volume":"501","author":"S Li","year":"2013","journal-title":"Nature"},{"key":"pone.0248975.ref035","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1128\/IAI.00771-10","article-title":"Discovery of novel secreted virulence factors from Salmonella enterica serovar Typhimurium by proteomic analysis of culture supernatants","volume":"79","author":"GS Niemann","year":"2011","journal-title":"Infect Immun"},{"key":"pone.0248975.ref036","doi-asserted-by":"crossref","first-page":"3525","DOI":"10.1016\/j.celrep.2018.05.072","article-title":"Salmonella activation of STAT3 signaling by SarA effector promotes intracellular replication and production of IL-10","volume":"23","author":"SL Jaslow","year":"2018","journal-title":"Cell Reports"},{"key":"pone.0248975.ref037","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1126\/science.aat7148","article-title":"Salmonella persisters undermine host immune defenses during antibiotic treatment","volume":"362","author":"DAC Stapels","year":"2018","journal-title":"Science"},{"key":"pone.0248975.ref038","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1111\/j.1462-5822.2011.01640.x","article-title":"The pathogenic Escherichia coli type III secreted protease NleC degrades the host acetyltransferase p300","volume":"13","author":"SR Shames","year":"2011","journal-title":"Cell Microbiol"},{"key":"pone.0248975.ref039","doi-asserted-by":"crossref","first-page":"3552","DOI":"10.1128\/IAI.05033-11","article-title":"Attaching and effacing bacterial effector NleC suppresses epithelial inflammatory responses by inhibiting NF-\u03baB and p38 mitogen-activated protein kinase activation","volume":"79","author":"HP Sham","year":"2011","journal-title":"Infect Immun"},{"key":"pone.0248975.ref040","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1111\/j.1365-2958.2011.07568.x","article-title":"A type III effector protease NleC from enteropathogenic Escherichia coli targets NF-\u03baB for degradation","volume":"80","author":"JS Pearson","year":"2011","journal-title":"Mol Microbiol"},{"key":"pone.0248975.ref041","doi-asserted-by":"crossref","first-page":"5100","DOI":"10.1074\/jbc.M110.172254","article-title":"Proteasome-independent degradation of canonical NFkappaB complex components by the NleC protein of pathogenic Escherichia coli","volume":"286","author":"S M\u00fchlen","year":"2011","journal-title":"J Biol Chem"},{"key":"pone.0248975.ref042","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/emboj.2010.297","article-title":"Metalloprotease type III effectors that specifically cleave JNK and NF-\u03baB","volume":"30","author":"K Baruch","year":"2011","journal-title":"The EMBO 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Microbiol"},{"key":"pone.0248975.ref046","doi-asserted-by":"crossref","first-page":"e1005262","DOI":"10.1371\/journal.ppat.1005262","article-title":"RNA-seq brings new insights to the intra-macrophage transcriptome of Salmonella Typhimurium","volume":"11","author":"S Srikumar","year":"2015","journal-title":"PLoS Pathog"},{"key":"pone.0248975.ref047","doi-asserted-by":"crossref","first-page":"602","DOI":"10.3389\/fimmu.2019.02822","article-title":"Salmonella Effector SteA suppresses proinflammatory responses of the host by interfering with I\u03baB degradation","volume":"10","author":"A Gulati","year":"2019","journal-title":"Front Immunol"},{"key":"pone.0248975.ref048","doi-asserted-by":"crossref","first-page":"e40645","DOI":"10.1371\/journal.pone.0040645","article-title":"Comparative genome analysis of the high pathogenicity Salmonella Typhimurium strain UK-1","volume":"7","author":"Y Luo","year":"2012","journal-title":"PLoS 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