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Polyketides, toxins and pigments in Penicillium marneffei.

Tam EW, Tsang CC, Lau SK, Woo PC - Toxins (Basel) (2015)

Bottom Line: This number is much higher than those of Coccidioides immitis and Histoplasma capsulatum, important pathogenic thermally dimorphic fungi in the Western world.Phylogenetically, these polyketide synthase genes were distributed evenly with their counterparts found in Aspergillus species and other fungi, suggesting that polyketide synthases in P. marneffei did not diverge from lineage-specific gene duplication through a recent expansion.Gene knockdown experiments and ultra-high performance liquid chromatography-photodiode array detector/electrospray ionization-quadruple time of flight-mass spectrometry analysis confirmed that at least four of the polyketide synthase genes were involved in the biosynthesis of various pigments in P. marneffei, including melanin, mitorubrinic acid, mitorubrinol, monascorubrin, rubropunctatin, citrinin and ankaflavin, some of which were mycotoxins and virulence factors of the fungus.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong. emily.wt@gmail.com.

ABSTRACT
Penicillium marneffei (synonym: Talaromyces marneffei) is the most important pathogenic thermally dimorphic fungus in China and Southeastern Asia. The HIV/AIDS pandemic, particularly in China and other Southeast Asian countries, has led to the emergence of P. marneffei infection as an important AIDS-defining condition. Recently, we published the genome sequence of P. marneffei. In the P. marneffei genome, 23 polyketide synthase genes and two polyketide synthase-non-ribosomal peptide synthase hybrid genes were identified. This number is much higher than those of Coccidioides immitis and Histoplasma capsulatum, important pathogenic thermally dimorphic fungi in the Western world. Phylogenetically, these polyketide synthase genes were distributed evenly with their counterparts found in Aspergillus species and other fungi, suggesting that polyketide synthases in P. marneffei did not diverge from lineage-specific gene duplication through a recent expansion. Gene knockdown experiments and ultra-high performance liquid chromatography-photodiode array detector/electrospray ionization-quadruple time of flight-mass spectrometry analysis confirmed that at least four of the polyketide synthase genes were involved in the biosynthesis of various pigments in P. marneffei, including melanin, mitorubrinic acid, mitorubrinol, monascorubrin, rubropunctatin, citrinin and ankaflavin, some of which were mycotoxins and virulence factors of the fungus.

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(A) Conidia suspensions of Penicillium marneffei wild type strain PM1 (left) and alb1-knockdown mutant (right). A loss of black pigment was observed in the conidia of the alb1-knockdown mutant; (B) Colony morphology of P. marneffei wild type strain PM1; (C) pks11-knockdown mutant; and (D) pks12-knockdown mutant on Sabouraud dextrose agar after 14 days of incubation at 25 °C. A loss of yellow pigment was observed in the conidia of the pks11- and pks12-knowckdown mutants; (E) Culture supernatants of P. marneffei wild type strain PM1 (left) and pks3-knockdown mutant (right) after 4 days of incubation in Sabouraud dextrose broth at 25 °C. A loss of red pigment production was observed for the pks3-knockdown mutant.
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toxins-07-04421-f002: (A) Conidia suspensions of Penicillium marneffei wild type strain PM1 (left) and alb1-knockdown mutant (right). A loss of black pigment was observed in the conidia of the alb1-knockdown mutant; (B) Colony morphology of P. marneffei wild type strain PM1; (C) pks11-knockdown mutant; and (D) pks12-knockdown mutant on Sabouraud dextrose agar after 14 days of incubation at 25 °C. A loss of yellow pigment was observed in the conidia of the pks11- and pks12-knowckdown mutants; (E) Culture supernatants of P. marneffei wild type strain PM1 (left) and pks3-knockdown mutant (right) after 4 days of incubation in Sabouraud dextrose broth at 25 °C. A loss of red pigment production was observed for the pks3-knockdown mutant.

Mentions: When alb1 was knocked down (KD), the isogenic P. marneffei mutant showed a loss of melanin in its conidia (Figure 2A), a reduction in the degree of ornamentation on the conidia surface, an attenuation of virulence in mouse model and a decrease in resistance to hydrogen peroxide killing [18]. The melanin biosynthetic gene cluster may contribute to virulence by reducing the fungal susceptibility to hydrogen peroxide killing [18]. In other pathogenic fungi, including A. fumigatus, P. brasiliensis and S. schenckii, loss of melanin production would decrease the susceptibility of the fungi to hydrogen peroxide killing, the capability to hide pathogenic substances, as well as the induction of cytokine response [25,31,36,44]. Hence, the loss of the pigment melanin may result in a reduction in fungal virulence. Some non-pathogenic fungi, such as T. stipitatus, also bear the melanin biosynthetic gene cluster. This likely suggests that resistance against hydrogen peroxide killing is only one of the steps that gives rise to its pathogenic property [18].


Polyketides, toxins and pigments in Penicillium marneffei.

Tam EW, Tsang CC, Lau SK, Woo PC - Toxins (Basel) (2015)

(A) Conidia suspensions of Penicillium marneffei wild type strain PM1 (left) and alb1-knockdown mutant (right). A loss of black pigment was observed in the conidia of the alb1-knockdown mutant; (B) Colony morphology of P. marneffei wild type strain PM1; (C) pks11-knockdown mutant; and (D) pks12-knockdown mutant on Sabouraud dextrose agar after 14 days of incubation at 25 °C. A loss of yellow pigment was observed in the conidia of the pks11- and pks12-knowckdown mutants; (E) Culture supernatants of P. marneffei wild type strain PM1 (left) and pks3-knockdown mutant (right) after 4 days of incubation in Sabouraud dextrose broth at 25 °C. A loss of red pigment production was observed for the pks3-knockdown mutant.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4663511&req=5

toxins-07-04421-f002: (A) Conidia suspensions of Penicillium marneffei wild type strain PM1 (left) and alb1-knockdown mutant (right). A loss of black pigment was observed in the conidia of the alb1-knockdown mutant; (B) Colony morphology of P. marneffei wild type strain PM1; (C) pks11-knockdown mutant; and (D) pks12-knockdown mutant on Sabouraud dextrose agar after 14 days of incubation at 25 °C. A loss of yellow pigment was observed in the conidia of the pks11- and pks12-knowckdown mutants; (E) Culture supernatants of P. marneffei wild type strain PM1 (left) and pks3-knockdown mutant (right) after 4 days of incubation in Sabouraud dextrose broth at 25 °C. A loss of red pigment production was observed for the pks3-knockdown mutant.
Mentions: When alb1 was knocked down (KD), the isogenic P. marneffei mutant showed a loss of melanin in its conidia (Figure 2A), a reduction in the degree of ornamentation on the conidia surface, an attenuation of virulence in mouse model and a decrease in resistance to hydrogen peroxide killing [18]. The melanin biosynthetic gene cluster may contribute to virulence by reducing the fungal susceptibility to hydrogen peroxide killing [18]. In other pathogenic fungi, including A. fumigatus, P. brasiliensis and S. schenckii, loss of melanin production would decrease the susceptibility of the fungi to hydrogen peroxide killing, the capability to hide pathogenic substances, as well as the induction of cytokine response [25,31,36,44]. Hence, the loss of the pigment melanin may result in a reduction in fungal virulence. Some non-pathogenic fungi, such as T. stipitatus, also bear the melanin biosynthetic gene cluster. This likely suggests that resistance against hydrogen peroxide killing is only one of the steps that gives rise to its pathogenic property [18].

Bottom Line: This number is much higher than those of Coccidioides immitis and Histoplasma capsulatum, important pathogenic thermally dimorphic fungi in the Western world.Phylogenetically, these polyketide synthase genes were distributed evenly with their counterparts found in Aspergillus species and other fungi, suggesting that polyketide synthases in P. marneffei did not diverge from lineage-specific gene duplication through a recent expansion.Gene knockdown experiments and ultra-high performance liquid chromatography-photodiode array detector/electrospray ionization-quadruple time of flight-mass spectrometry analysis confirmed that at least four of the polyketide synthase genes were involved in the biosynthesis of various pigments in P. marneffei, including melanin, mitorubrinic acid, mitorubrinol, monascorubrin, rubropunctatin, citrinin and ankaflavin, some of which were mycotoxins and virulence factors of the fungus.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong. emily.wt@gmail.com.

ABSTRACT
Penicillium marneffei (synonym: Talaromyces marneffei) is the most important pathogenic thermally dimorphic fungus in China and Southeastern Asia. The HIV/AIDS pandemic, particularly in China and other Southeast Asian countries, has led to the emergence of P. marneffei infection as an important AIDS-defining condition. Recently, we published the genome sequence of P. marneffei. In the P. marneffei genome, 23 polyketide synthase genes and two polyketide synthase-non-ribosomal peptide synthase hybrid genes were identified. This number is much higher than those of Coccidioides immitis and Histoplasma capsulatum, important pathogenic thermally dimorphic fungi in the Western world. Phylogenetically, these polyketide synthase genes were distributed evenly with their counterparts found in Aspergillus species and other fungi, suggesting that polyketide synthases in P. marneffei did not diverge from lineage-specific gene duplication through a recent expansion. Gene knockdown experiments and ultra-high performance liquid chromatography-photodiode array detector/electrospray ionization-quadruple time of flight-mass spectrometry analysis confirmed that at least four of the polyketide synthase genes were involved in the biosynthesis of various pigments in P. marneffei, including melanin, mitorubrinic acid, mitorubrinol, monascorubrin, rubropunctatin, citrinin and ankaflavin, some of which were mycotoxins and virulence factors of the fungus.

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Related in: MedlinePlus