Cited by 218Fungal Infections and StudiesEnzyme function and inhibitionFungal and yeast genetics research

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Carbonic Anhydrase and CO2 Sensing during Cryptococcus neoformans Growth, Differentiation, and Virulence

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Bahn, Yong-Sun, Cox, Gary M., Perfect, John R., Heitman, Joseph·2005·Current Biology

DOI 10.1016/j.cub.2005.09.047

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Abstract

The gas carbon dioxide (CO2) plays a critical role in microbial and mammalian respiration, photosynthesis in algae and plants, chemoreception in insects, and even global warming . However, how CO2 is transported, sensed, and metabolized by microorganisms is largely not understood. For instance, CO2 is known to induce production of polysaccharide capsule virulence determinants in pathogenic bacteria and fungi via unknown mechanisms . Therefore, we studied CO2 actions in growth, differentiation, and virulence of the basidiomycetous human fungal pathogen Cryptococcus neoformans. The CAN2 gene encoding beta-carbonic anhydrase in C. neoformans was found to be essential for growth in environmental ambient conditions but dispensable for in vivo proliferation and virulence at the high CO2 levels in the host. The can2Delta mutant in vitro growth defect is largely attributable to defective fatty acid synthesis. CO2 was found to inhibit cell-cell fusion but not filamentation during sexual reproduction. The can2 mutation restored early mating events in high CO2 but not later steps (fruiting body formation, sporulation), indicating a major role for carbonic anhydrase and CO2/HCO3- in this developmental cascade leading to the production of infectious spores. Our studies illustrate diverse roles of an ancient enzyme class in enabling environmental survival of a ubiquitous human pathogen.

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Authors: Bahn, Y.-S., Cox, G. M., Perfect, J. R., & Heitman, J.
Affiliations: Duke Medical Center (US)
Corresponding author: Heitman, Joseph
ORCID: Bahn, Yong-Sun
Perfect, John R.
Heitman, Joseph
Venue: Current Biology
Publisher: Elsevier BV
Published: 2005-11
Volume: 15
Issue: 22
Pages: 2013-2020
ISSN: 0960-9822 (ISSN-L)
DOI: 10.1016/j.cub.2005.09.047
OpenAlex: W1968110247
Cited by: 205
References: 47
Citations by year: 2026: 9 · 2025: 9 · 2024: 7 · 2023: 5 · 2022: 7 · 2021: 3 · 2020: 4 · 2019: 9 · 2018: 8 · 2017: 4 · 2016: 5 · 2015: 8 · 2014: 18 · 2013: 14 · 2012: 9
FWCI: 10.04
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 2815 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Current Biology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Allergy and Infectious Diseases (AI39115, AI44975, AI50113)
Topics: Health Sciences › Medicine › Infectious Diseases › Fungal Infections and Studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Enzyme function and inhibition
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Keywords: carbonic anhydrase, carbon dioxide detection, Cryptococcus neoformans, beta-carbonic anhydrase, fungal virulence, fatty acid synthesis, cell-cell fusion, sexual differentiation, mating, fruiting body formation, sporulation, human fungal pathogens, environmental survival
MeSH terms: Base Sequence, Bicarbonates, Carbon Dioxide, Carbonic Anhydrases, Cell Adhesion, Cryptococcus neoformans, DNA Mutational Analysis, Fatty Acids, Molecular Sequence Data, Mutation, Reproduction, Spores, Fungal, Blotting, Northern, Sequence Analysis, DNA, Computational Biology

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Carbonic Anhydrase and CO2 Sensing during Cryptococcus neoformans Growth, Differentiation, and Virulence

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