Redox buffering by melanin and Fe(II) in Cryptococcus neoformans

Jacobson, Eric S.; Hong, Joohyeon

doi:10.1128/jb.179.17.5340-5346.1997

Cited by 62 publications

(64 citation statements)

References 21 publications

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“…The relation between melanin and virulence has been studied extensively (31). Melanin can confer protection against extracellular redox buffering via the exporting of electrons, and this antioxidant function has been observed in C. neoformans (16,38,55), A. niger (22,23), E. dermatitidis (17,50), S. schenckii (44), and A. fumigatus (18,59). Melanin can also impact host-fungal cell interactions, since melanized cells are more resistant to phagocytosis than nonmelanized cells in P. brasiliensis (9,51) and other fungi (19,44,54).…”

Section: Discussionmentioning

confidence: 99%

Detection of Antibodies against Paracoccidioides brasiliensis Melanin inIn VitroandIn VivoStudies during Infection

Urán

Nosanchuk

Restrepo

et al. 2011

Clin. Vaccine Immunol.

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Several cell wall constituents, including melanins or melanin-like compounds, have been implicated in the pathogenesis of a wide variety of microbial diseases caused by diverse species of pathogenic bacteria, fungi, and helminthes. Among these microorganisms, the dimorphic fungal pathogen Paracoccidioides brasiliensis produces melanin in its conidial and yeast forms. In the present study, melanin particles from P. brasiliensis were injected into BALB/c mice in order to produce monoclonal antibodies (MAbs). We identified five immunoglobulin G1 (IgG1) -chain and four IgM melanin-binding MAbs. The five IgG1 -chain isotypes are the first melanin-binding IgG MAbs ever reported. The nine MAbs labeled P. brasiliensis conidia and yeast cells both in vitro and in pulmonary tissues. The MAbs cross-reacted with melanin-like purified particles from other fungi and also with commercial melanins, such as synthetic and Sepia officinalis melanin. Melanization during paracoccidioidomycosis (PCM) was also further supported by the detection of IgG antibodies reactive to melanin from P. brasiliensis conidia and yeast in sera and bronchoalveolar lavage fluids from P. brasiliensisinfected mice, as well as in sera from human patients with PCM. Serum specimens from patients with other mycoses were also tested for melanin-binding antibodies by enzyme-linked immunosorbent assay, and crossreactivities were detected for melanin particles from different fungal sources. These results suggest that melanin from P. brasiliensis is an immunologically active fungal structure that activates a strong IgG humoral response in humans and mice.

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Section: Discussionmentioning

confidence: 99%

Detection of Antibodies against Paracoccidioides brasiliensis Melanin inIn VitroandIn VivoStudies during Infection

Urán

Nosanchuk

Restrepo

et al. 2011

Clin. Vaccine Immunol.

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“…Currently, there are two previous reports of an association between microbial melanins and ferric reduction. In the first case to be described, pathogenic C. neoformans elaborates a surface-associated eumelanin that was shown to reduce ferric hydroxyl-EDTA (51,70,72). A recent study reports that iron levels can modulate the transcriptional control of melanin biosynthesis in C. neoformans (54).…”

Section: Discussionmentioning

confidence: 99%

The Secreted Pyomelanin Pigment of Legionella pneumophila Confers Ferric Reductase Activity

2007

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The virulence of Legionella pneumophila is dependent upon its capacity to acquire iron. To identify genes involved in expression of its siderophore, we screened a mutagenized population of L. pneumophila for strains that were no longer able to rescue the growth of a ferrous transport mutant. However, an unusual mutant was obtained that displayed a strong inhibitory effect on the feoB mutant. Due to an insertion in hmgA that encodes homogentisate 1,2-dioxygenase, the mutant secreted increased levels of pyomelanin, the L. pneumophila pigment that is derived from secreted homogentisic acid (HGA). Thus, we hypothesized that L. pneumophilasecreted HGA-melanin has intrinsic ferric reductase activity, converting Fe 3؉ to Fe 2؉ , but that hyperpigmentation results in excessive reduction of iron that can, in the case of the feoB mutant, be inhibitory to growth. In support of this hypothesis, we demonstrated, for the first time, that wild-type L. pneumophila secretes ferric reductase activity. Moreover, whereas the hyperpigmented mutant had increased secreted activity, an lly mutant specifically impaired for pigment production lacked the activity. Compatible with the nature of HGA-melanins, the secreted ferric reductase activity was positively influenced by the amount of tyrosine in the growth medium, resistant to protease, acid precipitable, and heterogeneous in size. Together, these data represent the first demonstration of pyomelanin-mediated ferric reduction by a pathogenic bacterium.Legionella pneumophila, an occupant of natural and humanmade aquatic environments, is also the principal agent of Legionnaires' disease, a serious form of pneumonia that especially afflicts immunocompromised individuals (18,37,41). In water habitats, this gram-negative bacterium survives free, in biofilms, and as an intracellular parasite of protozoa (2, 62, 65); in the lung, it replicates in alveolar macrophages (67,93,95). Among the processes that promote L. pneumophila growth in both the environment and the mammalian host are Lsp type II protein secretion, Dot/Icm type IVB protein secretion, and the Lvh type IVA protein secretion system (8,19,27,57,84,105). Other notable surface features of L. pneumophila include flagella, type IV pili, the major outer membrane protein porin, the Hsp60 chaperonin, and the Mip peptidylproline isomerase (9,26,39,46,49,66,88,99,108). In addition to exporting proteins and enzymes onto its surface or into the extracellular milieu and/or host cells, L. pneumophila also secretes a siderophore (legiobactin) that promotes iron uptake (3). Iron acquisition has long been regarded as a key aspect of L. pneumophila growth, intracellular infection, and virulence (12,17,82). Besides legiobactin, we have uncovered both FeoB ferrous iron transport, which is critical for bacterial growth in host cells and the lung, as well as the ccm, frgA, hbp, iraAB, and tat genes, which also promote L. pneumophila growth under low-iron conditions (20,47,68,73,81,86,87,106,107). The discovery of legiobactin has drawn further attention...

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“…This was shown, for example, in studies on oxidative damage of Wangiella dermatitidis and Cryptococcus neoformans and also on A. fumigatus conidia (3,(6)(7)(8). Therefore, it was conceivable that the apparent absence of oxidative burst by PMN in response to wt conidia of A. fumigatus or A. nidulans was due to a quenching effect of the wild-type pigments (11) ( Fig.…”

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confidence: 99%

Interaction of Human Phagocytes with Pigmentless Aspergillus Conidia

et al. 2000

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A defect in the pksP gene of Aspergillus fumigatus is associated with the loss of conidial pigmentation, a profound change of the conidial surface structure, and reduced virulence. The structural change of the conidial surface structure was not observed in similar A. nidulans wA mutants. Our data indicate that the pigment of both species is important for scavenging reactive oxygen species and for protection of conidia against oxidative damage.Aspergillus spp. are the predominant causative agents of invasive pulmonary aspergillosis (IPA), an often lethal infection of the immunocompromised host (4,10,13,16). Since conidia are the infectious agent in IPA, recent studies focused on the elucidation of conidial factors contributing to pathogenicity (8,17). Previously, we and others have shown that conidia lacking pigmentation due to the defective polyketide synthase gene pksP were less resistant to the attack by monocytes in vitro and showed reduced virulence in a murine animal model (8,9,17,18). During these studies, it became apparent that coincubation of human phagocytes with pksP mutant conidia resulted in a marked increase in the release of reactive oxygen species (ROS) compared with wild-type (wt) conidia (8). Since a defective pksP gene not only impaired conidial pigmentation but concomitantly resulted in profound alterations of the conidial surface (8, 9), the question arose as to whether the large amounts of ROS detected after incubation of phagocytes with pksP mutant conidia were due to a change in the activation pattern of the cells or, alternatively, reflected the lack of ROS quenching capacity caused by the loss of conidial pigment. To address this question, conidia of wt strains of both Aspergillus fumigatus and the nonpathogenic fungus Aspergillus nidulans were compared with their respective pigmentless mutant strains.The WA mutant of A. nidulans (strain WG370; wA3 bgaO biA1) lacking the conidial pigment due to a defective polyketide synthase gene (wA) was constructed by a sexual cross of appropriate parental strains (12) using standard genetic techniques (14). The wA gene product might have a function similar to that of the pksP gene product of A. fumigatus, although major differences between the pigment biosyntheses of the two Aspergillus species exist (2, 18; this study).As previously reported, conidia of the A. fumigatus wt strain showed a rough surface; i.e., they had an ornamentation which was lacking in the pksP mutant strain (8, 9) ( Fig. 1A and B). The A. nidulans wt conidia showed a similar ornamentation (Fig. 1C). In contrast to the pigmentless pksP mutant strain of A. fumigatus, however, similar pigmentless conidia of A. nidulans (wA) still exhibited the ornamentation characteristic of wild-type conidia (Fig. 1D). Taken together, the difference in surface structure between the A. fumigatus pksP mutant and the A. nidulans wA mutant further supports the assumption that different pathways exist for either conidial pigment biosynthesis or pigment deposition in the two species (1). As was noted p...

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Redox buffering by melanin and Fe(II) in Cryptococcus neoformans

Cited by 62 publications

References 21 publications

Detection of Antibodies against Paracoccidioides brasiliensis Melanin inIn VitroandIn VivoStudies during Infection

Detection of Antibodies against Paracoccidioides brasiliensis Melanin inIn VitroandIn VivoStudies during Infection

The Secreted Pyomelanin Pigment of Legionella pneumophila Confers Ferric Reductase Activity

Interaction of Human Phagocytes with Pigmentless Aspergillus Conidia

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