Impact of Melanin on Microbial Virulence and Clinical Resistance to Antimicrobial Compounds

Nosanchuk, Joshua D.; Casadevall, Arturo

doi:10.1128/aac.00545-06

Cited by 341 publications

(290 citation statements)

References 143 publications

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“…Melanin may protect bacteria and fungi from different types of stress, including toxic products such as H 2 O 2 , pesticides, heavy metals and antibiotics (Hoti & Balaraman, 1993;Hullo et al, 2001;Nosanchuk & Casadevall, 2006).…”

Section: Effect Of Hmga Inactivation On Resistance To H 2 O 2 and Antmentioning

confidence: 99%

Inactivation of the hmgA gene of Pseudomonas aeruginosa leads to pyomelanin hyperproduction, stress resistance and increased persistence in chronic lung infection

et al. 2009

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Clinical isolates of Pseudomonas aeruginosa that hyperproduce a dark-brown pigment are quite often found in the lungs of chronically infected patients, suggesting that they may have an adaptive advantage in chronic infections. We have screened a library of random transposon insertions in P. aeruginosa. Transposon insertions resulting in the hyperproduction of a darkbrown pigment were found to be located in the hmgA gene, which putatively encodes the enzyme homogentisate-1,2-dioxygenase. Complementation studies indicate that hmgA disruption is responsible for the hyperproduction of pyomelanin in both laboratory and clinical isolates. A relationship between hmgA disruption and adaptation to chronic infection was explored and our results show that the inactivation of hmgA produces a slight reduction of killing ability in an acute murine model of lung infection. On the other hand, it also confers decreased clearance and increased persistence in chronic lung infections. Whether pyomelanin production is the cause of the increased adaptation to chronicity or just a side effect of hmgA inactivation is a question to be studied in future; however, this adaptation is consistent with the higher resistance to oxidative stress conferred in vitro by the pyomelanin pigment. Our results clearly demonstrate that hmgA inactivation leads to a better adaptation to chronic infection, and strongly suggest that this mechanism may be exploited in naturally occurring P. aeruginosa strains.

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Section: Effect Of Hmga Inactivation On Resistance To H 2 O 2 and Antmentioning

confidence: 99%

Inactivation of the hmgA gene of Pseudomonas aeruginosa leads to pyomelanin hyperproduction, stress resistance and increased persistence in chronic lung infection

et al. 2009

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“…Some fungi like C. neoformans and several molds can produce melanin in the soil, and this characteristic may provide increased resistance to the environmental stressors [23,24]. Melanized C. neoformans is more resistant to ingestion by environmental amoeboid [25] or nematode [26] species.…”

Section: Introductionmentioning

confidence: 99%

“…Melanized C. neoformans is more resistant to ingestion by environmental amoeboid [25] or nematode [26] species. Melanins also protect fungi from hydrolytic enzymes [27], UV, solar or gamma radiation [28,29], extreme temperatures [30], and heavy metals and several other toxic compounds [reviewed in 24].…”

Section: Introductionmentioning

confidence: 99%

Melanin as a virulence factor of Paracoccidioides brasiliensis and other dimorphic pathogenic fungi: a minireview

et al. 2008

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Melanin pigments are substances produced by a broad variety of pathogenic microorganisms, including bacteria, fungi, and helminths. Microbes predominantly produce melanin pigment via tyrosinases, laccases, catecholases, and the polyketide synthase pathway. In fungi, melanin is deposited in the cell wall and cytoplasm, and melanin particles (''ghosts'') can be isolated from these fungi that have the same size and shape of the original cells. Melanin has been reported in several human pathogenic dimorphic fungi including Paracoccidioides brasiliensis, Sporothrix schenckii, Histoplasma capsulatum, Blastomyces dermatitidis, and Coccidioides posadasii. Melanization appears to contribute to virulence by reducing the susceptibility of melanized fungi to host defense mechanisms and antifungal drugs.

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“…In melanized cells, melanin is found in the cell wall of the yeast . Melanization of C. neoformans cells is associated with acquired resistance to polyene-and echinocandin-class drugs and may be responsible for the refractoriness to therapy (Nosanchuk & Casadevall, 2006).…”

Section: Introductionmentioning

confidence: 99%

Vesicle-associated melanization in Cryptococcus neoformans

et al. 2009

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Recently, several pathogenic fungi were shown to produce extracellular vesicles that contain various components associated with virulence. In the human pathogenic fungus Cryptococcus neoformans, these components included laccase, an enzyme that catalyses melanin synthesis. Spherical melanin granules have been observed in the cell wall of C. neoformans. Given that melanin granules have dimensions that are comparable to those of extracellular vesicles, and that metazoan organisms produce melanin in vesicular structures known as melanosomes, we investigated the role of vesicles in cryptococcal melanization. Extracellular vesicles melanized when incubated with the melanin precursor L-3,4-dihydroxyphenylalanine (L-DOPA). The kinetics of substrate incorporation into cells and vesicles was analysed using radiolabelled L-DOPA. The results indicated that substrate incorporation was different for cells and isolated vesicles. Acidgenerated melanin ghosts stained with lipophilic dyes, implying the presence of associated lipid. A model for C. neoformans melanization is proposed that accounts for these observations and provides a mechanism for the assembly of melanin into relatively uniform spherical particles stacked in an orderly arrangement in the cell wall.

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Impact of Melanin on Microbial Virulence and Clinical Resistance to Antimicrobial Compounds

Cited by 341 publications

References 143 publications

Inactivation of the hmgA gene of Pseudomonas aeruginosa leads to pyomelanin hyperproduction, stress resistance and increased persistence in chronic lung infection

Inactivation of the hmgA gene of Pseudomonas aeruginosa leads to pyomelanin hyperproduction, stress resistance and increased persistence in chronic lung infection

Melanin as a virulence factor of Paracoccidioides brasiliensis and other dimorphic pathogenic fungi: a minireview

Vesicle-associated melanization in Cryptococcus neoformans

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