{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:09:46Z","timestamp":1785424186171,"version":"3.56.0"},"reference-count":48,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100008982","name":"National Science Foundation","doi-asserted-by":"publisher","award":["2334708"],"award-info":[{"award-number":["2334708"]}],"id":[{"id":"10.13039\/501100008982","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008982","name":"National Science Foundation","doi-asserted-by":"publisher","award":["2334708"],"award-info":[{"award-number":["2334708"]}],"id":[{"id":"10.13039\/501100008982","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2025,7]]},"abstract":"ABSTRACT<\/jats:title>\n \n \n \n Histoplasma capsulatum<\/jats:italic>\n is a thermally dimorphic fungal pathogen. It causes approximately 500,000 infections annually in the United States.\n Histoplasma<\/jats:italic>\n is present as avirulent mycelia in the soil and transforms into pathogenic yeasts at the human body temperature upon inhalation. This elevated temperature triggers the expression of many virulence factors that enable\n Histoplasma<\/jats:italic>\n yeasts to survive and proliferate within immune cells (i.e., macrophages) in the human lungs. In addition to elevated temperature,\n Histoplasma<\/jats:italic>\n yeasts also experience other environmental changes within the mammalian host, such as elevated carbon dioxide (CO\n 2<\/jats:sub>\n ) (ambient air vs host tissues) during infection. However, the impact of elevated CO\n 2<\/jats:sub>\n on\n Histoplasma<\/jats:italic>\n yeasts remains completely unknown. In this study, our results showed that elevated CO\n 2<\/jats:sub>\n enhanced\n Histoplasma<\/jats:italic>\n \u2019s growth, particularly increasing its ability to utilize certain amino acids (e.g., alanine) as the sole carbon source. We also found that elevated CO\n 2<\/jats:sub>\n reduced\n Histoplasma<\/jats:italic>\n \u2019s susceptibility to antifungals\n in vitro<\/jats:italic>\n .\n Histoplasma<\/jats:italic>\n \u2019s enhanced growth and reduced antifungal susceptibility under elevated CO\n 2<\/jats:sub>\n were not pH-dependent. Our findings suggest that the elevated CO\n 2<\/jats:sub>\n within mammalian hosts could potentially enhance\n Histoplasma<\/jats:italic>\n \u2019s virulence. Future antifungal susceptibility tests for\n Histoplasma<\/jats:italic>\n should be performed at 5% CO\n 2<\/jats:sub>\n for clinically relevant results.\n <\/jats:p>\n \n IMPORTANCE<\/jats:title>\n \n The fungal pathogen\n Histoplasma capsulatum<\/jats:italic>\n lives in the soil.\n Histoplasma<\/jats:italic>\n spores can be inhaled and cause respiratory infections. The human body is vastly different from the soil. One of the major differences is the carbon dioxide (CO\n 2<\/jats:sub>\n ) concentration (0.04% in the ambient air vs 5% or above in the human body). Therefore, it is important to understand the impact of elevated CO\n 2<\/jats:sub>\n on\n Histoplasma<\/jats:italic>\n . We found that elevated CO\n 2<\/jats:sub>\n promotes\n Histoplasma<\/jats:italic>\n \u2019s growth, suggesting that elevated CO\n 2<\/jats:sub>\n could potentially enhance\n Histoplasma<\/jats:italic>\n \u2019s virulence during infection. Our results showed that elevated CO\n 2<\/jats:sub>\n reduces\n Histoplasma<\/jats:italic>\n \u2019s antifungal susceptibility, suggesting that antifungal susceptibility tests for\n Histoplasma<\/jats:italic>\n should be performed at elevated CO\n 2<\/jats:sub>\n for clinically relevant results.\n <\/jats:p>\n <\/jats:sec>\n <\/jats:sec>","DOI":"10.1128\/spectrum.03106-24","type":"journal-article","created":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T10:54:50Z","timestamp":1748602490000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Elevated carbon dioxide enhances the growth and reduces the antifungal susceptibility of\n Histoplasma capsulatum<\/i>"],"prefix":"10.1128","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9001-7636","authenticated-orcid":false,"given":"Qian","family":"Shen","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/049xfwy04","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biology, Rhodes College","place":["Memphis, USA"]},{"id":[{"id":"https:\/\/ror.org\/049xfwy04","id-type":"ROR","asserted-by":"publisher"}],"name":"Biochemistry and Molecular Biology Program, Rhodes College","place":["Memphis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelsey","family":"Steinmetz","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/049xfwy04","id-type":"ROR","asserted-by":"publisher"}],"name":"Biochemistry and Molecular Biology Program, Rhodes College","place":["Memphis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/mr.53.2.186-209.1989"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0003100"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3004404"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/s1286-4579(99)80084-7"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0308154"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00027-06"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007213"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.14-0175"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40475-015-0044-0"},{"key":"e_1_3_3_11_2","first-page":"743","article-title":"Epidemiological investigation of Histoplasma capsulatum infection in China","volume":"114","author":"Zhao B","year":"2001","unstructured":"Zhao B, Xia X, Yin J, Zhang X, Wu E, Shi Y, Tong M, Sun S, Gui X, Zhao Z, Feng X. 2001. 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