Effects of Iron on Extracellular and Intracellular Growth of
            <i>Penicillium marneffei</i>

Taramelli, Donatella; Brambilla, Sônia Domingues Santos; Sala, G; Bruccoleri, Alessandra; Tognazioli, Clara; Riviera-Uzielli, L.; Boelaert, Johan R.

doi:10.1128/iai.68.3.1724-1726.2000

Cited by 23 publications

(25 citation statements)

References 16 publications

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“…These results revealed that the drug's antifungal activity was due to an increase in the intravacuolar pH and a disruption of pH-dependent metabolic processes (156); the increase in pH within the phagocytic vacuole may directly reduce fungal growth, or it may inhibit pH-dependent yeast virulence factors, such as acid phosphatase activity. In addition, iron overload was found to significantly reduce the antifungal activity of gamma interferon-lipopolysaccharide-activated human THP1 and mouse J774 macrophages (155). That work suggested that iron availability critically affects immunity and the pathogenicity of P. marneffei.…”

Section: Immunologymentioning

confidence: 79%

Penicillium marneffeiInfection and Recent Advances in the Epidemiology and Molecular Biology Aspects

et al. 2006

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SUMMARY Penicillium marneffei infection is an important emerging public health problem, especially among patients infected with human immunodeficiency virus in the areas of endemicity in southeast Asia, India, and China. Within these regions, P. marneffei infection is regarded as an AIDS-defining illness, and the severity of the disease depends on the immunological status of the infected individual. Early diagnosis by serologic and molecular assay-based methods have been developed and are proving to be important in diagnosing infection. The occurrence of natural reservoirs and the molecular epidemiology of P. marneffei have been studied; however, the natural history and mode of transmission of the organism remain unclear. Soil exposure, especially during the rainy season, has been suggested to be a critical risk factor. Using a highly discriminatory molecular technique, multilocus microsatellite typing, to characterize this fungus, several isolates from bamboo rats and humans were shown to share identical multilocus genotypes. These data suggest either that transmission of P. marneffei may occur from rodents to humans or that rodents and humans are coinfected from common environmental sources. These putative natural cycles of P. marneffei infection need further investigation. Studies on the fungal genetics of P. marneffei have been focused on the characterization of genetic determinants that may play important roles in asexual development, mycelial-to-yeast phase transition, and the expression of antigenic determinants. Molecular studies have identified several genes involved in germination, hyphal development, conidiogenesis, and yeast cell polarity. A number of functionally important genes, such as the malate synthase- and catalase-peroxidase protein-encoding genes, have been identified as being upregulated in the yeast phase. Future investigations pertaining to the roles of these genes in host-fungus interactions may provide the key knowledge to understanding the pathogenicity of P. marneffei.

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Section: Immunologymentioning

confidence: 79%

Penicillium marneffeiInfection and Recent Advances in the Epidemiology and Molecular Biology Aspects

et al. 2006

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“…Fetal bovine serum (FBS) has been shown to inhibit the growth of Penicillium marneffei (43), while the growth of Candida albicans (26) and the growth of Cryptococcus neoformans (14,32) are inhibited by human serum. Other fungal pathogens whose growth is inhibited by normal human serum include Histoplasma capsulatum (41), members of the genera Cunninghamella and Absidia (13), Rhizopus oryzae (3), and Rhizopus microsporus var.…”

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confidence: 99%

Serum Stimulates Growth of and Proteinase Secretion byAspergillus fumigatus

2002

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Serum contains iron-binding proteins, which inhibit the growth of most pathogenic microorganisms, including fungi. The purpose of this research was to investigate the effect of serum on growth of the opportunistic fungal pathogen Aspergillus fumigatus. Supplementing minimal essential medium (MEM) with up to 80% human serum or up to 80% fetal bovine serum (FBS) stimulated growth and increased the amount of A. fumigatus dry biomass approximately fourfold. In addition, a 100-fold increase in proteinase secretion, as measured by azocasein hydrolysis, was observed when 10% human serum or 10% FBS was added to MEM. The fungal proteinases secreted in serum-containing media were shown to degrade 3 H-labeled basal lamina proteins. The factor in serum that stimulated proteinase secretion was larger than 10 kDa and was 85% inactivated when the serum was heated for 30 min at 66°C. The proportions of proteinases of each catalytic class secreted by A. fumigatus in the presence of serum were different from the proportions secreted in media containing single proteins. Proteinase secretion did not result from increased protein concentration in the medium per se because bovine serum albumin (BSA) at a concentration equivalent to the concentration of serum produced only 20% of the proteinase activity per milligram (dry weight) that was produced by FBS. Addition of BSA plus 100 M FeCl 3 to MEM resulted in the same level of growth as addition of serum, indicating that a combination of nutritional factors in serum may stimulate growth. However, the level of proteinase secretion was still only 30% of the level observed with FBS. These data indicate that serum does not inhibit the growth of A. fumigatus and that the nutrients in serum result in high levels of proteinase secretion, potentially increasing the invasiveness of this species.

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“…A large body of evidence links the severity and/or progression of cellular pathogenesis to cellular iron status (2,8,10,13,15,16,48). However, little is known about possible underlying mechanisms of this linkage.…”

Section: Fig 9 Bypyridyl Inhibits Hsv-1 Infection As Effectively Asmentioning

confidence: 99%

“…Pathogens and their hosts share this ambiguous relationship with iron (7)(8)(9)(10)(11)(12)(13). However, pathogens live within the context of the iron-restricted milieu that the host maintains as a key to the suppression of the cytotoxic potential of iron.…”

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confidence: 99%

Intracellular Chelation of Iron by Bipyridyl Inhibits DNA Virus Replication

Romeo

Christen

Niles

et al. 2001

Journal of Biological Chemistry

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The efficient replication of large DNA viruses requires dNTPs supplied by a viral ribonucleotide reductase. Viral ribonucleotide reductase is an early gene product of both vaccinia and herpes simplex virus. For productive infection, the apoprotein must scavenge iron from the endogenous, labile iron pool(s). The membrane-permeant, intracellular Fe 2؉ chelator, 2,2-bipyridine (bipyridyl, BIP), is known to sequester iron from this pool. We show here that BIP strongly inhibits the replication of both vaccinia and herpes simplex virus, type 1. In a standard plaque assay, 50 M BIP caused a 50% reduction in plaque-forming units with either virus. Strong inhibition was observed only when BIP was added within 3 h post-infection. This time dependence was observed also in regards to inhibition of viral late protein and DNA synthesis by BIP. BIP did not inhibit the activity of vaccinia ribonucleotide reductase (RR), its synthesis, nor its stability indicating that BIP blocked the activation of the apoprotein. In parallel with its inhibition of vaccinia RR activation, BIP treatment increased the RNA binding activity of the endogenous iron-response protein, IRP1, by 1.9-fold. The data indicate that the diiron prosthetic group in vaccinia RR is assembled from iron taken from the BIP-accessible, labile iron pool that is sampled also by ferritin and the iron-regulated protein found in the cytosol of mammalian cells.

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Effects of Iron on Extracellular and Intracellular Growth of Penicillium marneffei

Cited by 23 publications

References 16 publications

Penicillium marneffeiInfection and Recent Advances in the Epidemiology and Molecular Biology Aspects

Penicillium marneffeiInfection and Recent Advances in the Epidemiology and Molecular Biology Aspects

Serum Stimulates Growth of and Proteinase Secretion byAspergillus fumigatus

Intracellular Chelation of Iron by Bipyridyl Inhibits DNA Virus Replication

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