{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T02:02:05Z","timestamp":1793152925398,"version":"4.5.0"},"reference-count":49,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2024,3,26]],"date-time":"2024-03-26T00:00:00Z","timestamp":1711411200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,3,26]],"date-time":"2024-03-26T00:00:00Z","timestamp":1711411200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R01AI143197, R01AI158442, R21AI178048"],"award-info":[{"award-number":["R01AI143197, R01AI158442, R21AI178048"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mSphere"],"published-print":{"date-parts":[[2024,3,26]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              <jats:italic>Aspergillus fumigatus<\/jats:italic>\n              is a major invasive mold pathogen and the most frequent etiologic agent of invasive aspergillosis. The currently available treatments for invasive aspergillosis are limited in both number and efficacy. Our recent work has uncovered that the \u03b2-glucan synthase inhibitors, the echinocandins, are fungicidal against strains of\n              <jats:italic>A. fumigatus<\/jats:italic>\n              with defects in septation initiation network (SIN) kinase activity. These drugs are known to be fungistatic against strains with normal septation. Surprisingly, SIN kinase mutant strains also failed to invade lung tissue and were significantly less virulent in immunosuppressed mouse models. Inhibiting septation in filamentous fungi is therefore an exciting therapeutic prospect to both reduce virulence and improve current antifungal therapy. However, the SIN remains understudied in pathogenic fungi. To address this knowledge gap, we characterized the putative regulatory components of the\n              <jats:italic>A. fumigatus<\/jats:italic>\n              SIN. These included the GTPase, SpgA, it\u2019s two-component GTPase-activating protein, ByrA\/BubA, and the kinase activators, SepM and MobA. Deletion of\n              <jats:italic>spgA<\/jats:italic>\n              ,\n              <jats:italic>byrA,<\/jats:italic>\n              or\n              <jats:italic>bubA<\/jats:italic>\n              resulted in no overt septation or echinocandin susceptibility phenotypes. In contrast, our data show that deletion of\n              <jats:italic>sepM<\/jats:italic>\n              or\n              <jats:italic>mobA<\/jats:italic>\n              largely phenocopies disruption of their SIN kinase binding partners,\n              <jats:italic>sepL<\/jats:italic>\n              and\n              <jats:italic>sidB<\/jats:italic>\n              , respectively. Reduced septum formation, echinocandin hypersusceptibility, and reduced virulence were generated by loss of either gene. These findings provide strong supporting evidence that septa are essential not only for withstanding the cell wall disrupting effects of echinocandins but are also critical for the establishment of invasive disease. Therefore, pharmacological SIN inhibition may be an exciting strategy for future antifungal drug development.\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>\n                Septa are important structural determinants of echinocandin susceptibility and tissue invasive growth for the ubiquitous fungal pathogen\n                <jats:italic>Aspergillus fumigatus<\/jats:italic>\n                . Components of the septation machinery therefore represent promising novel antifungal targets to improve echinocandin activity and reduce virulence. However, little is known about septation regulation in\n                <jats:italic>A. fumigatus<\/jats:italic>\n                . Here, we characterize the predicted regulatory components of the\n                <jats:italic>A. fumigatus<\/jats:italic>\n                septation initiation network. We show that the kinase activators SepM and MobA are vital for proper septation and echinocandin resistance, with MobA playing an essential role. Null mutants of\n                <jats:italic>mobA<\/jats:italic>\n                displayed significantly reduced virulence in a mouse model, underscoring the importance of this pathway for\n                <jats:italic>A. fumigatus<\/jats:italic>\n                pathogenesis.\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/msphere.00695-23","type":"journal-article","created":{"date-parts":[[2024,2,13]],"date-time":"2024-02-13T14:01:15Z","timestamp":1707832875000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":12,"title":["MOB-mediated regulation of septation initiation network (SIN) signaling is required for echinocandin-induced hyperseptation in\n            <i>Aspergillus fumigatus<\/i>"],"prefix":"10.1128","volume":"9","author":[{"given":"Harrison I.","family":"Thorn","sequence":"first","affiliation":[{"name":"Graduate Program in Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, USA"},{"name":"Department of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3258-2482","authenticated-orcid":false,"given":"Xabier","family":"Guruceaga","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0446-8906","authenticated-orcid":false,"given":"Adela","family":"Martin-Vicente","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley V.","family":"Nywening","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, USA"},{"name":"Integrated Program in Biomedical Sciences, College of Graduate Health Sciences, University of Tennessee Health Science Center, Memphis, Tennessee, USA"},{"name":"Department of Microbiology, Immunology, and Biochemistry, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhong","family":"Xie","sequence":"additional","affiliation":[{"name":"Graduate Program in Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, USA"},{"name":"Department of Clinical Pharmacy and Translational Science, College of Pharmacy, University of 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