Gliotoxin production by Aspergillus fumigatus strains from animal environment. Micro-analytical sample treatment combined with a LC-MS/MS method for gliotoxin determination

Pena, Gabriela Alejandra; Monge, M.P.; Pereyra, M.L. González; Dalcero, Ana María; Rosa, Carlos A.; Chiacchiera, Stella Maris; Cavaglieri, Lilia Reneé

doi:10.1007/s12550-015-0225-7

Cited by 6 publications

(3 citation statements)

References 20 publications

(24 reference statements)

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“…Analysis of a gliotoxin standard (Fig. 1C) showed that it elutes at 3.30 min with an accurate mass of 327.0464 Da (2.8 ppm) and has key fragments of 263.1 Da and 245.1 Da, in accord with values reported in the literature (20).…”

supporting

confidence: 85%

Gliotoxin, a Known Virulence Factor in the Major Human Pathogen Aspergillus fumigatus, Is Also Biosynthesized by Its Nonpathogenic Relative Aspergillus fischeri

Knowles

Mead

Silva

et al. 2020

mBio

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Aspergillus fumigatus is a major opportunistic human pathogen. Multiple traits contribute to A. fumigatus pathogenicity, including its ability to produce specific secondary metabolites, such as gliotoxin. Gliotoxin is known to inhibit the host immune response, and genetic mutants that inactivate gliotoxin biosynthesis (or secondary metabolism in general) attenuate A. fumigatus virulence. The genome of Aspergillus fischeri, a very close nonpathogenic relative of A. fumigatus, contains a biosynthetic gene cluster that is homologous to the A. fumigatus gliotoxin cluster. However, A. fischeri is not known to produce gliotoxin. To gain further insight into the similarities and differences between the major pathogen A. fumigatus and the nonpathogen A. fischeri, we examined whether A. fischeri strain NRRL 181 biosynthesizes gliotoxin and whether the production of secondary metabolites influences the virulence profile of A. fischeri. We found that A. fischeri biosynthesizes gliotoxin under the same conditions as A. fumigatus. However, whereas loss of laeA, a master regulator of secondary metabolite production (including gliotoxin biosynthesis), has previously been shown to reduce A. fumigatus virulence, we found that laeA loss (and loss of secondary metabolite production) in A. fischeri does not influence its virulence. These results suggest that LaeA-regulated secondary metabolites are virulence factors in the genomic and phenotypic background of the major pathogen A. fumigatus but are much less important in the background of the nonpathogen A. fischeri. Understanding the observed spectrum of pathogenicity across closely related pathogenic and nonpathogenic Aspergillus species will require detailed characterization of their biological, chemical, and genomic similarities and differences. IMPORTANCE Aspergillus fumigatus is a major opportunistic fungal pathogen of humans, but most of its close relatives are nonpathogenic. Why is that so? This important, yet largely unanswered, question can be addressed by examining how A. fumigatus and its close nonpathogenic relatives are similar or different with respect to virulence-associated traits. We investigated whether Aspergillus fischeri, a nonpathogenic close relative of A. fumigatus, can produce gliotoxin, a mycotoxin known to contribute to A. fumigatus virulence. We discovered that the nonpathogenic A. fischeri produces gliotoxin under the same conditions as those of the major pathogen A. fumigatus. However, we also discovered that, in contrast to what has previously been observed in A. fumigatus, the loss of secondary metabolite production in A. fischeri does not alter its virulence. Our results are consistent with the “cards of virulence” model of opportunistic fungal disease, in which the ability to cause disease stems from the combination (“hand”) of virulence factors (“cards”) but not from individual factors per se.

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supporting

confidence: 85%

Gliotoxin, a Known Virulence Factor in the Major Human Pathogen Aspergillus fumigatus, Is Also Biosynthesized by Its Nonpathogenic Relative Aspergillus fischeri

Knowles

Mead

Silva

et al. 2020

mBio

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“…Analysis of a gliotoxin standard ( Fig. 1C ) showed that it elutes at 3.30 minutes, with an accurate mass of 327.0464 Da (2.8 ppm) and has key fragments of 263.1 Da and 245.1 Da, in accord with values reported in the literature (18).…”

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confidence: 85%

Gliotoxin, a known virulence factor in the major human pathogen Aspergillus fumigatus, is also biosynthesized by the non-pathogenic relative A. fischeri

Knowles¹,

Mead

Silva

et al. 2019

Preprint

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2Gliotoxin, a known virulence factor in the major human pathogen Aspergillus fumigatus, is 3 also biosynthesized by the non-pathogenic relative A. fischeri 4 5 ABSTRACT 21Aspergillus fumigatus is a major opportunistic human pathogen. Multiple traits contribute to A. 22 fumigatus pathogenicity, including its ability to produce specific secondary metabolites, such as 23 gliotoxin. Gliotoxin is known to inhibit the host immune response, and genetic mutants that 24 inactivate gliotoxin biosynthesis (or secondary metabolism in general) attenuate A. fumigatus 25 virulence. The genome of A. fischeri, a very close non-pathogenic relative of A. fumigatus, 26 contains a biosynthetic gene cluster that exhibits high sequence similarity to the A. fumigatus 27 gliotoxin cluster. However, A. fischeri is not known to produce gliotoxin. To gain further insight 28 into the similarities and differences between the major pathogen A. fumigatus and the non-29 pathogen A. fischeri, we examined whether A. fischeri strain NRRL 181 biosynthesizes gliotoxin 30 and whether its production, and of secondary metabolites more generally, influence its virulence 31 profile. We found that A. fischeri biosynthesizes gliotoxin in the same conditions as A. 32 fumigatus. However, whereas loss of laeA, a master regulator of secondary metabolite 33 production, has been previously shown to reduce the virulence of A. fumigatus, we found that 34 laeA loss (and loss of secondary metabolite production, including gliotoxin) in A. fischeri does 35 not influence its virulence. These results suggest that gliotoxin and secondary metabolite 36 production are virulence factors in the genomic and phenotypic background of the major 37 pathogen A. fumigatus but are much less important in the background of the non-pathogen A. 38 fischeri. We submit that understanding the observed spectrum of pathogenicity across closely 39 related pathogenic and non-pathogenic Aspergillus species will require detailed characterization 40 of their biological, chemical, and genomic similarities and differences. 41 IMPORTANCE 42Aspergillus fumigatus is a major opportunistic fungal pathogen of humans but most of its close 43 relatives are non-pathogenic. Why is that so? This important, yet largely unanswered, question 44 can be addressed by examining how A. fumigatus and its non-pathogenic close relatives are 45 similar or different with respect to virulence-associated traits. We investigated whether 46Aspergillus fischeri, a non-pathogenic close relative of A. fumigatus, can produce gliotoxin, a 47

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“…Gliotoxin ( Figure 8A ), a mycotoxin produced by Aspergillus fumigatus , can cause immunosuppression, genotoxicity, cytotoxicity, and apoptosis ( Pena et al, 2015 ). Gliotoxin is synthesized by the gliotoxin oxidase GliT and can therefore be reverse degraded via its synthetic pathway ( Dolan et al, 2017 ).…”

Section: Common Mycotoxins and Corresponding Enzymes Used For Detoxif...mentioning

confidence: 99%

Bioenzymatic detoxification of mycotoxins

Liu,

Zhang,

Luan

et al. 2024

Front. Microbiol.

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Mycotoxins are secondary metabolites produced during the growth, storage, and transportation of crops contaminated by fungi and are physiologically toxic to humans and animals. Aflatoxin, zearalenone, deoxynivalenol, ochratoxin, patulin, and fumonisin are the most common mycotoxins and can cause liver and nervous system damage, immune system suppression, and produce carcinogenic effects in humans and animals that have consumed contaminated food. Physical, chemical, and biological methods are generally used to detoxify mycotoxins. Although physical methods, such as heat treatment, irradiation, and adsorption, are fast and simple, they have associated problems including incomplete detoxification, limited applicability, and cause changes in food characteristics (e.g., nutritive value, organoleptic properties, and palatability). Chemical detoxification methods, such as ammonification, ozonation, and peroxidation, pollute the environment and produce food safety risks. In contrast, bioenzymatic methods are advantageous as they achieve selective detoxification and are environmentally friendly and reusable; thus, these methods are the most promising options for the detoxification of mycotoxins. This paper reviews recent research progress on common mycotoxins and the enzymatic principles and mechanisms for their detoxification, analyzes the toxicity of the degradation products and describes the challenges faced by researchers in carrying out enzymatic detoxification. In addition, the application of enzymatic detoxification in food and feed is discussed and future directions for the development of enzymatic detoxification methods are proposed for future in-depth study of enzymatic detoxification methods.

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Gliotoxin production by Aspergillus fumigatus strains from animal environment. Micro-analytical sample treatment combined with a LC-MS/MS method for gliotoxin determination

Cited by 6 publications

References 20 publications

Gliotoxin, a Known Virulence Factor in the Major Human Pathogen Aspergillus fumigatus, Is Also Biosynthesized by Its Nonpathogenic Relative Aspergillus fischeri

Gliotoxin, a Known Virulence Factor in the Major Human Pathogen Aspergillus fumigatus, Is Also Biosynthesized by Its Nonpathogenic Relative Aspergillus fischeri

Gliotoxin, a known virulence factor in the major human pathogen Aspergillus fumigatus, is also biosynthesized by the non-pathogenic relative A. fischeri

Bioenzymatic detoxification of mycotoxins

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