{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:29:37Z","timestamp":1791296977613,"version":"4.1.0"},"reference-count":56,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2013,8,13]],"date-time":"2013-08-13T00:00:00Z","timestamp":1376352000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2013,8,30]],"date-time":"2013-08-30T00:00:00Z","timestamp":1377820800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2013,8,30]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Does cell age matter in virulence? The emergence of persister cells during chronic infections is critical for persistence of infection, but little is known how this occurs. Here, we demonstrate for the first time that the replicative age of the fungal pathogen\n            <jats:named-content content-type=\"genus-species\">Cryptococcus neoformans<\/jats:named-content>\n            contributes to persistence during chronic meningoencephalitis. Generationally older\n            <jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>\n            cells are more resistant to hydrogen peroxide stress, macrophage intracellular killing, and antifungal agents. Older cells accumulate in both experimental rat infection and in human cryptococcosis. Mathematical modeling supports the concept that the presence of older\n            <jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>\n            cells emerges from\n            <jats:italic>in vivo<\/jats:italic>\n            selection pressures. We propose that advanced replicative aging is a new unanticipated virulence trait that emerges during chronic fungal infection and facilitates persistence. Therapeutic interventions that target old cells could help in the clearance of chronic infections.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Our findings that the generational age of\n            <jats:named-content content-type=\"genus-species\">Cryptococcus neoformans<\/jats:named-content>\n            cells matters in pathogenesis introduces a novel concept to eukaryotic pathogenesis research. We propose that emerging properties of aging\n            <jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>\n            cells and possibly also other fungal pathogens contribute to persistence and virulence. Whereas the replicative life span of strains may not matter for virulence\n            <jats:italic>per se<\/jats:italic>\n            , age-related resilience and thus the generational age of individual\n            <jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>\n            cells within a pathogen population could greatly affect persistence of the pathogen population and therefore impact outcome.\n          <\/jats:p>","DOI":"10.1128\/mbio.00455-13","type":"journal-article","created":{"date-parts":[[2013,8,14]],"date-time":"2013-08-14T03:01:42Z","timestamp":1376449302000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":46,"title":["Old Cryptococcus neoformans Cells Contribute to Virulence in Chronic Cryptococcosis"],"prefix":"10.1128","volume":"4","author":[{"given":"Tejas","family":"Bouklas","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ximo","family":"Pechuan","sequence":"additional","affiliation":[{"name":"Department of Systems and Computational Biology, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L.","family":"Goldman","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York, USA"},{"name":"Department of Pediatrics, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Batya","family":"Edelman","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aviv","family":"Bergman","sequence":"additional","affiliation":[{"name":"Department of Systems and Computational Biology, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York, USA"},{"name":"Dominick P. 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