{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T01:49:37Z","timestamp":1790905777609,"version":"4.1.0"},"reference-count":21,"publisher":"Microbiology Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1996,4,1]]},"abstract":"<jats:p>\n                  <jats:italic>Cryptococcus neoformans<\/jats:italic> produces large amounts of the acyclic hexitol mannitol in culture and infected animals, but the functional and pathogenic significance of mannitol production by this fungus is not known. We exposed <jats:italic>C. neoformans<\/jats:italic> H99 (Cn H99) to UV irradiation (1 \u00d7 LD<jats:sub>50<\/jats:sub>) and screened survivors for mannitol production. A mutant, Cn MLP (Mannitol Low Producer), synthesized less mannitol from glucose (2.7 vs 8.2 nmol per 10<jats:sup>8<\/jats:sup> cells min<jats:sup>\u22121<\/jats:sup> at 37 \u00b0) and contained less intracellular mannitol (1 vs 11 \u03bcmol per 10<jats:sup>6<\/jats:sup> cells at 37 \u00b0) than did Cn H99. Cn MLP and Cn H99 were similar with respect to carbon assimilation patterns, rates of glucose consumption, growth rates at 30 \u00b0, urease and phenoloxidase activities, morphology, capsule formation, mating type, electrophoretic karyotype, rapid amplification of polymorphic DNA (RAPD) patterns and antifungal susceptibility. However, Cn MLP was more susceptible than was Cn H99 to growth inhibition and killing by heat and high NaCl concentrations. Also, the LD<jats:sub>50<\/jats:sub> values in mice injected intravenously were 3.7 \u00d7 10<jats:sup>6<\/jats:sup> c.f.u. for Cn MLP compared to 6.9 \u00d7 10<jats:sup>2<\/jats:sup> c.f.u. for Cn H99. Moreover, 500 c.f.u. Cn H99 intravenously killed 12 of 12 mice by 60 d, whereas all mice given the same inoculum of Cn MLP survived. Classical genetic studies were undertaken to determine if these differences were due to a single mutation, but the basidiospores were nonviable. These results suggest that the abilities of <jats:italic>C. neoformans<\/jats:italic> to produce and accumulate mannitol may influence its tolerance to heat and osmotic stresses and its pathogenicity in mice.<\/jats:p>","DOI":"10.1099\/00221287-142-4-937","type":"journal-article","created":{"date-parts":[[2009,6,5]],"date-time":"2009-06-05T04:53:32Z","timestamp":1244177612000},"page":"937-943","source":"Crossref","is-referenced-by-count":92,"title":["Stress tolerance and pathogenic potential of a mannitol mutant of Cryptococcus neoformans"],"prefix":"10.1099","volume":"142","author":[{"given":"Vishnu","family":"Chaturvedi","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Yale University School of Medicine and Infectious Diseases Section, VA Connecticut Medical Center, 950 Campbell Avenue, 111-1, West Haven, CT 06516, USA"},{"name":"Division of Infectious Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0560, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Flynn","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Anaerobic Microbiology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061-0308, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter G.","family":"Niehaus","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Anaerobic Microbiology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061-0308, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Yale University School of Medicine and Infectious Diseases Section, VA Connecticut Medical Center, 950 Campbell Avenue, 111-1, West Haven, CT 06516, USA"},{"name":"Division of Infectious Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0560, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"345","reference":[{"key":"R1","doi-asserted-by":"crossref","first-page":"4135","DOI":"10.1128\/MCB.14.6.4135","article-title":"GPD1, which encodes glycerol-3-phosphate dehydrogenase, is essential for growth under osmotic stress in Saccharomyces cerevisiae, and its expression is regulated by the high-osmolarity glycerol response pathway","volume":"14","author":"Albertyn","year":"1994","journal-title":"Mol Cell Biol"},{"key":"R2","first-page":"277","article-title":"Standard media for cultivation of yeasts","volume-title":"Yeast","author":"Campbell","year":"1988"},{"key":"R3","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1056\/NEJM198909213211205","article-title":"Infections with Cryptococcus neoformans in acquired immunodeficiency syndrome","volume":"321","author":"Chuck","year":"1989","journal-title":"N Engl J Med"},{"key":"R4","doi-asserted-by":"crossref","first-page":"4801","DOI":"10.1128\/IAI.61.11.4801-4813.1993","article-title":"Genetic stability and diversity of Pneumocystis carinii infecting rat colonies","volume":"61","author":"Cushion","year":"1993","journal-title":"Infect Immun"},{"key":"R5","first-page":"3453","article-title":"Yeast water relations: physiological changes induced by solute stress in Saccharomyces cerevisiae and Saccharomyces rouxii","volume":"129","author":"Edgley","year":"1983","journal-title":"J Gen Microbiol"},{"key":"R6","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/S0065-2911(08)60292-1","article-title":"Polyol metabolism in fungi","volume":"25","author":"Jennings","year":"1984","journal-title":"Adv Microb Physiol"},{"key":"R7","first-page":"397","article-title":"Cryptococcosis","volume-title":"Medical Mycology","author":"Kwon-Chung","year":"1992"},{"key":"R8","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1139\/m93-087","article-title":"The role of physiological state in osmotolerance of the salt-tolerant yeast Debaryomyces hansenii","volume":"39","author":"Larsson","year":"1993","journal-title":"Can J Microbiol"},{"key":"R9","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1111\/j.1365-2958.1993.tb00980.x","article-title":"A gene encoding sn-glycerol 3-phosphate dehydrogenase (NAD+) complements an osmosensitive mutant of Saccharomyces cerevisiae","volume":"10","author":"Larsson","year":"1993","journal-title":"Mol Microbiol"},{"key":"R10","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1093\/clinids\/13.6.1163","article-title":"The ecology of Cryptococcus neoformans and the epidemiology of cryptococcosis","volume":"13","author":"Levitz","year":"1991","journal-title":"Rev Infect Dis"},{"key":"R11","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1099\/13500872-141-3-687","article-title":"Induction of heat, freezing and salt tolerance by heat and salt shock in Saccharomyces cerevisiae","volume":"141","author":"Lewis","year":"1995","journal-title":"Microbiol"},{"key":"R12","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1111\/j.1365-2958.1993.tb01951.x","article-title":"Osmostress response of the yeast Saccharomyces","volume":"10","author":"Mager","year":"1993","journal-title":"Mol Microbiol"},{"key":"R13","doi-asserted-by":"crossref","first-page":"1962","DOI":"10.1128\/MCB.13.3.1962","article-title":"The alpha-mating type locus of Cryptococcus neoformans contains a peptide pheromone gene","volume":"13","author":"Moore","year":"1993","journal-title":"Mol Cell Biol"},{"key":"R14","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1128\/JB.176.3.651-655.1994","article-title":"Regulation of mannitol biosynthesis and degradation by Cryptococcus neoformans","volume":"176","author":"Niehaus","year":"1994","journal-title":"J Bacteriol"},{"key":"R15","first-page":"444","article-title":"A cryptic gene encodes mannitol dehydrogenase in Saccharomyces cerevisiae","volume":"8","author":"Niehaus","year":"1994","journal-title":"FASEB J"},{"key":"R16","first-page":"177","article-title":"Chronic cryptococcal meningitis: a new experimental model in rabbits","volume":"101","author":"Perfect","year":"1980","journal-title":"Am J Pathol"},{"key":"R17","first-page":"493","article-title":"A simple method of estimating fifty percent end points","volume":"27","author":"Reed","year":"1938","journal-title":"Am J Hyg"},{"key":"R18","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1111\/j.1574-6968.1988.tb03200.x","article-title":"Physiological overlap between osmotolerance and thermotolerance in Saccharomyces cerevisiae","volume":"56","author":"Trollmo","year":"1988","journal-title":"FEMS Microbiol Lett"},{"key":"R19","doi-asserted-by":"crossref","first-page":"7091","DOI":"10.1128\/JB.176.22.7091-7095.1994","article-title":"Cloning, sequencing and disruption of the Saccharomyces diastaticus DARI gene encoding a glycerol-3-phosphate dehydrogenase","volume":"176","author":"Wang","year":"1994","journal-title":"I Bacteriol"},{"key":"R20","doi-asserted-by":"crossref","first-page":"7213","DOI":"10.1093\/nar\/18.24.7213","article-title":"Fingerprinting genomes using PCR with arbitrary primers","volume":"18","author":"Welsh","year":"1990","journal-title":"Nucleic Acids Rix"},{"key":"R21","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1128\/IAI.58.6.1664-1670.1990","article-title":"Production of hexitol D-mannitol by Cryptococcus neoformans in vitro and in rabbits with experimental meningitis","volume":"58","author":"Wong","year":"1990","journal-title":"Infect Immun"}],"container-title":["Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/micro\/10.1099\/00221287-142-4-937?crawler=true","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,16]],"date-time":"2021-03-16T04:24:54Z","timestamp":1615868694000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/micro\/10.1099\/00221287-142-4-937"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,4,1]]},"references-count":21,"journal-issue":{"issue":"4","published-print":{"date-parts":[[1996,4,1]]}},"URL":"https:\/\/doi.org\/10.1099\/00221287-142-4-937","relation":{},"ISSN":["1350-0872","1465-2080"],"issn-type":[{"value":"1350-0872","type":"print"},{"value":"1465-2080","type":"electronic"}],"subject":[],"published":{"date-parts":[[1996,4,1]]}}}