Microbial Transformation of Phenazines by Aspergillus Sclerotiorum

Hill, James C.; Johnson, G. T.

doi:10.1080/00275514.1969.12018758

Cited by 10 publications

(9 citation statements)

References 14 publications

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“…One report describes the production of an extracellular red pigment, with different properties from the pigment described here, that forms in cocultures of Aspergillus sclerotiorum and Pseudomonas chlororaphis, suggesting that other fungi may be able to modify certain bacterially produced phenazines (17); the biological activity of the modified P. chlororaphis phenazine is not known. One can envision many ways in which modification or aggregation of phenazines after secretion by the producing microbe could enhance or reduce the toxicity of the antibiotic, and these processes may be important factors to consider in the design of phenazine-producing biocontrol strains.…”

Section: Discussionmentioning

confidence: 99%

Pseudomonas aeruginosa - Candida albicans Interactions: Localization and Fungal Toxicity of a Phenazine Derivative

Gibson

Sood

Hogan

2009

Appl Environ Microbiol

188

186

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Phenazines are redox-active small molecules that play significant roles in the interactions between pseudomonads and diverse eukaryotes, including fungi. When Pseudomonas aeruginosa and Candida albicans were cocultured on solid medium, a red pigmentation developed that was dependent on P. aeruginosa phenazine biosynthetic genes. Through a genetic screen in combination with biochemical experiments, it was found that a P. aeruginosa-produced precursor to pyocyanin, proposed to be 5-methyl-phenazinium-1-carboxylate (5MPCA), was necessary for the formation of the red pigmentation. The 5MPCA-derived pigment was found to accumulate exclusively within fungal cells, where it retained the ability to be reversibly oxidized and reduced, and its detection correlated with decreased fungal viability. Pyocyanin was not required for pigment formation or fungal killing. Spectral analyses showed that the partially purified pigment from within the fungus differed from aeruginosins A and B, two red phenazine derivatives formed late in P. aeruginosa cultures. The red pigment isolated from C. albicans that had been cocultured with P. aeruginosa was heterogeneous and difficult to release from fungal cells, suggesting its modification within the fungus. These findings suggest that intracellular targeting of some phenazines may contribute to their toxicity and that this strategy could be useful in developing new antifungals.

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Section: Discussionmentioning

confidence: 99%

Pseudomonas aeruginosa - Candida albicans Interactions: Localization and Fungal Toxicity of a Phenazine Derivative

Gibson

Sood

Hogan

2009

Appl Environ Microbiol

188

186

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“…This is a remarkable result, because although phenazines have been studied for decades and are toxic to various organisms, few studies have detailed bioconversion or sequestering of these metabolites by other species. One relevant example is the reported conversion of PCN (13) and PCA (3) to a partially characterized phenazine by A. sclerotiorum (38). More recently, fungal addition products to 5-MPCA were observed in the interaction of C. albicans with P. aeruginosa, resulting in increased fungal toxicity (31,39).…”

Section: Biotransformation Of P Aeruginosa Phenazine Metabolites By Amentioning

confidence: 99%

Interkingdom metabolic transformations captured by microbial imaging mass spectrometry

Moree

Phelan

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

221

241

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In polymicrobial infections, microbes can interact with both the host immune system and one another through direct contact or the secretion of metabolites, affecting disease progression and treatment options. The thick mucus in the lungs of patients with cystic fibrosis is highly susceptible to polymicrobial infections by opportunistic pathogens, including the bacterium Pseudomonas aeruginosa and the fungus Aspergillus fumigatus. Unravelling the hidden molecular interactions within such polymicrobial communities and their metabolic exchange processes will require effective enabling technologies applied to model systems. In the present study, MALDI-TOF and MALDI-FT-ICR imaging mass spectrometry (MALDI-IMS) combined with MS/MS networking were used to provide insight into the interkingdom interaction between P. aeruginosa and A. fumigatus at the molecular level. The combination of these technologies enabled the visualization and identification of metabolites secreted by these microorganisms grown on agar. A complex molecular interplay was revealed involving suppression, increased production, and biotransformation of a range of metabolites. Of particular interest is the observation that P. aeruginosa phenazine metabolites were converted by A. fumigatus into other chemical entities with alternative properties, including enhanced toxicities and the ability to induce fungal siderophores. This work highlights the capabilities of MALDI-IMS and MS/MS network analysis to study interkingdom interactions and provides insight into the complex nature of polymicrobial metabolic exchange and biotransformations. M icrobes that colonize mammalian hosts can form polymicrobial communities, such as biofilms, where they establish commensual, mutualistic, competitive, or antagonistic interactions with one another and with the host. In microbial disease, this complex interplay can affect the outcome of antimicrobial therapy (1). Therefore, it is important to understand polymicrobial populations and their interactions at the molecular level.In persons with cystic fibrosis (CF), the lungs are lined with a viscous mucus layer susceptible to polymicrobial infections (2). Pseudomonas aeruginosa, a Gram-negative bacterial opportunistic pathogen, is the most prevalent and persistent microorganism (3) isolated from the sputum of CF lungs and leading cause of mortality in CF patients (4). Within the CF lung, P. aeruginosa exists in biofilm-like macrocolonies (5) and is refractory to antimicrobial agents and the host immune response (6). Aspergillus fumigatus, an opportunistic fungal pathogen, is the second-most persistent microbe in the CF lung, with a 10-57% prevalence rate (3), and is capable of causing allergic bronchopulmonary aspergillosis (7).Superinfection with both P. aeruginosa and A. fumigatus in CF patients leads to decreased pulmonary function compared with monoinfection with either microbe (8). Interestingly, however, in a pulmonary mouse model, mice coinfected with P. aeruginosa and A. fumigatus had a higher survival rate than mice...

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“…Isolates of A. ochraceus or A. sclerotiorum are useful for biochemical transformation of steroids, alkaloids, or phenazines (Chen et al, 1994;Petroski et al, 1983;Hill and Johnson, 1969). Some species, e.g., A. sclerotiorum and A. melleus, are important sources of proteolytic enzymes (Kundu et al, 1974;Luisetti et al, 1991) and other metabolites (Matsukuma et al, 1992;Lin et al, 1995), while sclerotia of several species contain anti-insectan compounds (Wicklow et al, 1994;Whyte et al, 1996;Ooike et al, 1997).…”

mentioning

confidence: 97%

Phylogenetic Analysis of Aspergillus Section Circumdati Based on Sequences of the Internal Transcribed Spacer Regions and the 5.8 S rRNA Gene

Varga

Töth

Rigó

et al. 2000

Fungal Genetics and Biology

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Microbial Transformation of Phenazines by Aspergillus Sclerotiorum

Cited by 10 publications

References 14 publications

Pseudomonas aeruginosa - Candida albicans Interactions: Localization and Fungal Toxicity of a Phenazine Derivative

Pseudomonas aeruginosa - Candida albicans Interactions: Localization and Fungal Toxicity of a Phenazine Derivative

Interkingdom metabolic transformations captured by microbial imaging mass spectrometry

Phylogenetic Analysis of Aspergillus Section Circumdati Based on Sequences of the Internal Transcribed Spacer Regions and the 5.8 S rRNA Gene

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