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Metabolites released by Cryptococcus neoformans var. neoformans and var. gattii differentially affect human neutrophil function.
Microbes Infect. 2002 Nov; 4(14):1427-38.MI

Abstract

Differences in the ability of Cryptococcus neoformans var. neoformans (CNVN) and var. gattii (CNVG) to establish localized lesions in the lungs of healthy humans remain unexplained. In this study, CNVG infection in a rat model was characterized by early neutrophil invasion into lung tissue, but phagocytosis of cryptococci was not observed. The chemical composition of non-enzymic components secreted by one strain of each variety (heat-inactivated supernatants from CNVN and CNVG, termed vns and vgs, respectively) were compared, using magnetic resonance spectroscopy. Effects on human neutrophil viability and functions at both pH 5.5 and 7.0 were investigated, as the pH of cryptococcomas was found to be 5.4-5.6 in vivo. The supernatants were similar in composition, although metabolites in vns were generally present in higher concentrations. In addition, vgs contained two novel metabolites-acetoin and dihydroxyacetone. Polyphosphate was observed in cells from both varieties and may be a source of extracellular inorganic phosphate. Superoxide production in the presence of phorbol ester was enhanced by treatment with vns and decreased by vgs. At pH 5.5, vns caused high levels of necrosis in neutrophils, as well as increased adhesion/migration through A549 lung epithelial cell monolayers. Individual supernatant components such as polyols, acetoin, dihydroxyacetone, and gamma-aminobutyric acid exhibited both pro- and anti-inflammatory properties. Overall, we found that vgs was potentially less pro-inflammatory than vns. Inhibition of neutrophil function by products of CNVG may promote survival of extracellular organisms, and local multiplication to form cryptococcomas.

Authors+Show Affiliations

Wright L
Department of Infectious Diseases, Center for Infectious Diseases and Microbiology, Level 3, ICPMR Building, University of Sydney, Westmead Hospital, Westmead, NSW 2145, Australia. lesleyw@icpmr.wsahs.nsw.gov.au
Bubb W
No affiliation info available
Davidson J
No affiliation info available
Santangelo R
No affiliation info available
Krockenberger M
No affiliation info available
Himmelreich U
No affiliation info available
Sorrell T
No affiliation info available

MeSH

AnimalsAntigens, FungalBiological FactorsCell AdhesionCell MovementCryptococcosisCryptococcus neoformansFemaleHumansHydrogen-Ion ConcentrationLung Diseases, FungalNeutrophilsPhosphatesRatsRats, Inbred F344SuperoxidesTime Factors

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12475633

Citation

Wright, Lesley, et al. "Metabolites Released By Cryptococcus Neoformans Var. Neoformans and Var. Gattii Differentially Affect Human Neutrophil Function." Microbes and Infection, vol. 4, no. 14, 2002, pp. 1427-38.
Wright L, Bubb W, Davidson J, et al. Metabolites released by Cryptococcus neoformans var. neoformans and var. gattii differentially affect human neutrophil function. Microbes Infect. 2002;4(14):1427-38.
Wright, L., Bubb, W., Davidson, J., Santangelo, R., Krockenberger, M., Himmelreich, U., & Sorrell, T. (2002). Metabolites released by Cryptococcus neoformans var. neoformans and var. gattii differentially affect human neutrophil function. Microbes and Infection, 4(14), 1427-38.
Wright L, et al. Metabolites Released By Cryptococcus Neoformans Var. Neoformans and Var. Gattii Differentially Affect Human Neutrophil Function. Microbes Infect. 2002;4(14):1427-38. PubMed PMID: 12475633.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Metabolites released by Cryptococcus neoformans var. neoformans and var. gattii differentially affect human neutrophil function. AU - Wright,Lesley, AU - Bubb,William, AU - Davidson,John, AU - Santangelo,Rosemary, AU - Krockenberger,Mark, AU - Himmelreich,Uwe, AU - Sorrell,Tania, PY - 2002/12/12/pubmed PY - 2003/3/11/medline PY - 2002/12/12/entrez SP - 1427 EP - 38 JF - Microbes and infection JO - Microbes Infect VL - 4 IS - 14 N2 - Differences in the ability of Cryptococcus neoformans var. neoformans (CNVN) and var. gattii (CNVG) to establish localized lesions in the lungs of healthy humans remain unexplained. In this study, CNVG infection in a rat model was characterized by early neutrophil invasion into lung tissue, but phagocytosis of cryptococci was not observed. The chemical composition of non-enzymic components secreted by one strain of each variety (heat-inactivated supernatants from CNVN and CNVG, termed vns and vgs, respectively) were compared, using magnetic resonance spectroscopy. Effects on human neutrophil viability and functions at both pH 5.5 and 7.0 were investigated, as the pH of cryptococcomas was found to be 5.4-5.6 in vivo. The supernatants were similar in composition, although metabolites in vns were generally present in higher concentrations. In addition, vgs contained two novel metabolites-acetoin and dihydroxyacetone. Polyphosphate was observed in cells from both varieties and may be a source of extracellular inorganic phosphate. Superoxide production in the presence of phorbol ester was enhanced by treatment with vns and decreased by vgs. At pH 5.5, vns caused high levels of necrosis in neutrophils, as well as increased adhesion/migration through A549 lung epithelial cell monolayers. Individual supernatant components such as polyols, acetoin, dihydroxyacetone, and gamma-aminobutyric acid exhibited both pro- and anti-inflammatory properties. Overall, we found that vgs was potentially less pro-inflammatory than vns. Inhibition of neutrophil function by products of CNVG may promote survival of extracellular organisms, and local multiplication to form cryptococcomas. SN - 1286-4579 UR - https://www.unboundmedicine.com/medline/citation/12475633/Metabolites_released_by_Cryptococcus_neoformans_var__neoformans_and_var__gattii_differentially_affect_human_neutrophil_function_ DB - PRIME DP - Unbound Medicine ER -