{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:29:35Z","timestamp":1783038575257,"version":"3.54.6"},"reference-count":68,"publisher":"American Society for Microbiology","license":[{"start":{"date-parts":[[2023,7,11]],"date-time":"2023-07-11T00:00:00Z","timestamp":1689033600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,7,11]],"date-time":"2023-07-11T00:00:00Z","timestamp":1689033600000},"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":["R03-AI111015"],"award-info":[{"award-number":["R03-AI111015"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R01-AI148561"],"award-info":[{"award-number":["R01-AI148561"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Peroxisomes are versatile eukaryotic organelles essential for many functions in fungi, including fatty acid metabolism, reactive oxygen species detoxification, and secondary metabolite biosynthesis. A suite of Pex proteins (peroxins) maintains peroxisomes, while peroxisomal matrix enzymes execute peroxisome functions. Insertional mutagenesis identified peroxin genes as essential components supporting the intraphagosomal growth of the fungal pathogen\n            <jats:italic>Histoplasma capsulatum<\/jats:italic>\n            . Disruption of the peroxins Pex5, Pex10, or Pex33 in\n            <jats:italic>H. capsulatum<\/jats:italic>\n            prevented peroxisome import of proteins targeted to the organelle via the PTS1 pathway. This loss of peroxisome protein import limited\n            <jats:italic>H. capsulatum<\/jats:italic>\n            intracellular growth in macrophages and attenuated virulence in an acute histoplasmosis infection model. Interruption of the alternate PTS2 import pathway also attenuated\n            <jats:italic>H. capsulatum<\/jats:italic>\n            virulence, although only at later time points of infection. The Sid1 and Sid3 siderophore biosynthesis proteins contain a PTS1 peroxisome import signal and localize to the\n            <jats:italic>H. capsulatum<\/jats:italic>\n            peroxisome. Loss of either the PTS1 or PTS2 peroxisome import pathway impaired siderophore production and iron acquisition in\n            <jats:italic>H. capsulatum<\/jats:italic>\n            , demonstrating compartmentalization of at least some biosynthetic steps for hydroxamate siderophore biosynthesis. However, the loss of PTS1-based peroxisome import caused earlier virulence attenuation than either the loss of PTS2-based protein import or the loss of siderophore biosynthesis, indicating additional PTS1-dependent peroxisomal functions are important for\n            <jats:italic>H. capsulatum<\/jats:italic>\n            virulence. Furthermore, disruption of the Pex11 peroxin also attenuated\n            <jats:italic>H. capsulatum<\/jats:italic>\n            virulence independently of peroxisomal protein import and siderophore biosynthesis. These findings demonstrate peroxisomes contribute to\n            <jats:italic>H. capsulatum<\/jats:italic>\n            pathogenesis by facilitating siderophore biosynthesis and another unidentified role(s) for the organelle during fungal virulence.\n          <\/jats:p>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              The fungal pathogen\n              <jats:italic>Histoplasma capsulatum<\/jats:italic>\n              infects host phagocytes and establishes a replication-permissive niche within the cells. To do so,\n              <jats:italic>H. capsulatum<\/jats:italic>\n              overcomes and subverts antifungal defense mechanisms which include the limitation of essential micronutrients.\n              <jats:italic>H. capsulatum<\/jats:italic>\n              replication within host cells requires multiple distinct functions of the fungal peroxisome organelle. These peroxisomal functions contribute to\n              <jats:italic>H. capsulatum<\/jats:italic>\n              pathogenesis at different times during infection and include peroxisome-dependent biosynthesis of iron-scavenging siderophores to enable fungal proliferation, particularly after activation of cell-mediated immunity. The multiple essential roles of fungal peroxisomes reveal this organelle as a potential but untapped target for the development of therapeutics.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/mbio.03284-22","type":"journal-article","created":{"date-parts":[[2023,7,11]],"date-time":"2023-07-11T13:07:20Z","timestamp":1689080840000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":10,"title":["<i>Histoplasma capsulatum<\/i>\n            requires peroxisomes for multiple virulence functions including siderophore biosynthesis"],"prefix":"10.1128","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7632-3725","authenticated-orcid":true,"given":"Peter J.","family":"Brechting","sequence":"first","affiliation":[{"name":"Department of Microbiology, Ohio State University , Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandan","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Ohio State University , Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liva","family":"Rakotondraibe","sequence":"additional","affiliation":[{"name":"Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Ohio State University , Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9001-7636","authenticated-orcid":true,"given":"Qian","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Biology, Rhodes College , Memphis, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7880-5958","authenticated-orcid":true,"given":"Chad A.","family":"Rappleye","sequence":"additional","affiliation":[{"name":"Department of Microbiology, 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