Nutritional studies of histoplasma capsulatum

McVeigh, Ilda; Morton, Katherine

doi:10.1007/bf02049917

Cited by 38 publications

(17 citation statements)

References 11 publications

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“…1C) tamin B 7 (biotin), and vitamin B 9 (folate). Previous studies of the nutritional requirements for Histoplasma yeast growth indicated that most strains do not require nutritional supplementation with essential vitamins with the possible exception of thiamine (58). Some strains were auxotrophic for niacin, pantothenate, and/or biotin, but all were able to grow without added riboflavin, folate, and pyridoxine.…”

Section: Isolation Of a Histoplasma Riboflavin Auxotroph From A Genetmentioning

confidence: 99%

Histoplasma capsulatum Depends on De Novo Vitamin Biosynthesis for Intraphagosomal Proliferation

2014

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During infection of the mammalian host, Histoplasma capsulatum yeasts survive and reside within macrophages of the immune system. Whereas some intracellular pathogens escape into the host cytosol, Histoplasma yeasts remain within the macrophage phagosome. This intracellular Histoplasma-containing compartment imposes nutritional challenges for yeast growth and replication. We identified and annotated vitamin synthesis pathways encoded in the Histoplasma genome and confirmed by growth in minimal medium that Histoplasma yeasts can synthesize all essential vitamins with the exception of thiamine. Riboflavin, pantothenate, and biotin auxotrophs of Histoplasma were generated to probe whether these vitamins are available to intracellular yeasts. Disruption of the RIB2 gene (riboflavin biosynthesis) prevented growth and proliferation of yeasts in macrophages and severely attenuated Histoplasma virulence in a murine model of respiratory histoplasmosis. Rib2-deficient yeasts were not cleared from lung tissue but persisted, consistent with functional survival mechanisms but inability to replicate in vivo. In addition, depletion of Pan6 (pantothenate biosynthesis) but not Bio2 function (biotin synthesis) also impaired Histoplasma virulence. These results indicate that the Histoplasma-containing phagosome is limiting for riboflavin and pantothenate and that Histoplasma virulence requires de novo synthesis of these cofactor precursors. Since mammalian hosts do not rely on vitamin synthesis but instead acquire essential vitamins through diet, vitamin synthesis pathways represent druggable targets for therapeutics.

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Section: Isolation Of a Histoplasma Riboflavin Auxotroph From A Genetmentioning

confidence: 99%

Histoplasma capsulatum Depends on De Novo Vitamin Biosynthesis for Intraphagosomal Proliferation

2014

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“…The acid-treated glassware was rinsed extensively in double-distilled deionized water. Liquid shake cultures were grown in the synthetic medium devised by McVeigh and Morton (MM) (15). MM medium was depleted of iron by treatment with the cationic exchange resin Chelex 100 (BioRad Laboratories, Richmond, Calif.).…”

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confidence: 99%

Hydroxamate Siderophores of Histoplasma capsulatum

Howard¹,

Rafiee²,

Tiwari³

et al. 2000

Infect Immun

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The zoopathogenic fungus Histoplasma capsulatum, like other eukaryotic aerobic microorganisms, requires iron for growth. Under conditions of low iron availability, the fungus secretes hydroxamates that function as siderophores (iron chelators). The experiments to be reported were designed to gather further information on the hydroxamate siderophores of H. capsulatum. The fungus was grown in a synthetic medium deferrated with the cationic exchange resin Chelex 100. Siderophores were detected after 4 days of incubation at 37°C in media containing 0.3 to 1.0 M iron. The secretion was suppressed by 10 M iron. The hydroxamates were purified by reverse-phase and size-exclusion chromatography. On the basis of ions observed during electrospray mass spectroscopy, five hydroxamate siderophores were tentatively identified: dimerum acid, acetyl dimerum acid, coprogen B, methyl coprogen B, and fusarinine (monomeric). A polyclonal antibody to dimerum acid was generated. This reagent cross-reacted with coprogen B and fusarinine. Thus, the antibody detects hydroxamates in all three families of siderophores excreted by H. capsulatum.

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“…The role of cysteine or cystine in initiation and maintenance of the yeast phase of growth of H. capsulatum has been of interest to many researchers. Although Scherr (12) suggested that these amino acids may act by lowering the oxidation-reduction (O-R) potential of the medium, it appears that a nutritional role may also be involved, because other compounds which are capable of lowering the O-R potential (glutathione or thioglycolate) are not effective in maintaining yeast-phase growth (7,11). Nevertheless, more recent work has reemphasized the critical role of the O-R potential of a medium in the yeast-mold dimorphism of H. capsulatum (10).…”

Section: Discussionmentioning

confidence: 99%

Uptake of Cystine by the Yeast Phase of Histoplasma capsulatum

Gilbert

Howard

1970

Infect Immun

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This report deals with factors affecting the uptake of cystine by the yeast phase of Histoplasma capsulatum . The kinetics of uptake showed a saturation at 70 μM and an average K m value of 3 × 10 −5 m . The optimal p H and temperature for transport of cystine were 6.5 and 37 C, respectively. The energy of activation was 14.1 kcal/mole, and the temperature coefficient value was 2.1. A requirement for energy supplied by metabolic activity was demonstrated by the inhibition of incorporation of the amino acid by cells preincubated with either 2,4-dinitrophenol or sodium azide. Although uptake was not inhibited by any single amino acid, a combination of amino acids did cause a decrease in uptake. Thus, the data show that the uptake of cystine by yeast cells of H. capsulatum has the characteristics of a system of transport that requires the expenditure of energy by the cells.

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Nutritional studies of histoplasma capsulatum

Cited by 38 publications

References 11 publications

Histoplasma capsulatum Depends on De Novo Vitamin Biosynthesis for Intraphagosomal Proliferation

Histoplasma capsulatum Depends on De Novo Vitamin Biosynthesis for Intraphagosomal Proliferation

Hydroxamate Siderophores of Histoplasma capsulatum

Uptake of Cystine by the Yeast Phase of Histoplasma capsulatum

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