Toxins of Filamentous Fungi

Bhatnagar, Deepak; Yu, Jiujiang; Ehrlich, Kenneth C.

doi:10.1159/000058867

Cited by 142 publications

(83 citation statements)

References 128 publications

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“…Tip growth in this genus is particularly important because some species (e.g., A. niger and A. oryzae) produce economically important This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E07-05-0464) on January 23, 2008. products, whereas others (e.g., A. fumigatus) are serious pathogens, particularly in immune-compromised patients (reviewed by Brookman and Denning, 2000;Latge 2001). Still other species (e.g., A. flavus) cause contamination of foods with toxic and carcinogenic aflatoxins (reviewed by Bhatnagar et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

The Tip Growth Apparatus ofAspergillus nidulans

Taheri-Talesh

Horio

Araújo‐Bazán

et al. 2008

MBoC

273

414

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Hyphal tip growth in fungi is important because of the economic and medical importance of fungi, and because it may be a useful model for polarized growth in other organisms. We have investigated the central questions of the roles of cytoskeletal elements and of the precise sites of exocytosis and endocytosis at the growing hyphal tip by using the model fungus Aspergillus nidulans. Time-lapse imaging of fluorescent fusion proteins reveals a remarkably dynamic, but highly structured, tip growth apparatus. Live imaging of SYNA, a synaptobrevin homologue, and SECC, an exocyst component, reveals that vesicles accumulate in the Spitzenkö rper (apical body) and fuse with the plasma membrane at the extreme apex of the hypha. SYNA is recycled from the plasma membrane by endocytosis at a collar of endocytic patches, 1-2 m behind the apex of the hypha, that moves forward as the tip grows. Exocytosis and endocytosis are thus spatially coupled. Inhibitor studies, in combination with observations of fluorescent fusion proteins, reveal that actin functions in exocytosis and endocytosis at the tip and in holding the tip growth apparatus together. Microtubules are important for delivering vesicles to the tip area and for holding the tip growth apparatus in position. INTRODUCTIONPolarized cell growth occurs in most eukaryotic phyla, and it includes a plethora of important phenomena, such as neuronal growth cone extension in animals and pollen tube extension in vascular plants. It is particularly important in filamentous fungi where nearly all growth occurs by hyphal tip extension (reviewed by Momany, 2002). Given that some filamentous fungi are important fermentation organisms, the growth of which is of considerable economic importance, whereas others are serious plant, animal, and human pathogens, there is considerable interest in the mechanisms of tip growth in these organisms.A great deal of progress has been made in understanding fungal tip growth (summarized by Harris et al., 2005; Steinberg, 2007a,b;Riquelme et al., 2007), but key questions remain unanswered. There is general agreement that fungal tip growth involves the synthesis of cell wall components in the cell body, the incorporation of these components into vesicles, the transport of these vesicles to the cell tip, the fusion of these vesicles with the plasma membrane in the area of the cell tip (exocytosis) to release their contents, and the cross-linking of the components after release. It is clear that both microtubules and actin microfilaments play important roles in fungal tip growth, but their exact functions are not yet defined. The exact sites of exocytosis and endocytosis also remain to be determined. The positions of the site(s) of exocytosis are particularly important because fungal walls are relatively stiff structures, and once they have formed the shape of the hypha is established. Hyphal shape is thus determined to a very significant extent by where the wall precursors are released from the cytoplasm, i.e., by the positioning of the site(s) of exocyto...

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Section: Introductionmentioning

confidence: 99%

The Tip Growth Apparatus ofAspergillus nidulans

Taheri-Talesh

Horio

Araújo‐Bazán

et al. 2008

MBoC

273

414

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“…Economically and biologically the most important fungal species able to produce aflatoxins are Aspergillus flavus and Aspergillus parasiticus [1]. The aflatoxin biosynthesis gene cluster of A. parasiticus has been completely elucidated [2][3][4].…”

Section: Introductionmentioning

confidence: 99%

A systems approach to model the relationship between aflatoxin gene cluster expression, environmental factors, growth and toxin production by Aspergillus flavus

Abdel-Hadi

Schmidt‐Heydt

Parra‐Saldívar

et al. 2011

J. R. Soc. Interface.

133

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A microarray analysis was used to examine the effect of combinations of water activity (a w , 0.995-0.90) and temperature (20 -428C) on the activation of aflatoxin biosynthetic genes (30 genes) in Aspergillus flavus grown on a conducive YES (20 g yeast extract, 150 g sucrose, 1 g MgSO 4 . 7H 2 O) medium. The relative expression of 10 key genes (aflF, aflD, aflE, aflM, aflO, aflP, aflQ, aflX, aflR and aflS) in the biosynthetic pathway was examined in relation to different environmental factors and phenotypic aflatoxin B 1 (AFB 1 ) production. These data, plus data on relative growth rates and AFB 1 production under different a w Â temperature conditions were used to develop a mixed-growth-associated product formation model. The gene expression data were normalized and then used as a linear combination of the data for all 10 genes and combined with the physical model. This was used to relate gene expression to a w and temperature conditions to predict AFB 1 production. The relationship between the observed AFB 1 production provided a good linear regression fit to the predicted production based in the model. The model was then validated by examining datasets outside the model fitting conditions used (378C, 408C and different a w levels). The relationship between structural genes (aflD, aflM) in the biosynthetic pathway and the regulatory genes (aflS, aflJ) was examined in relation to a w and temperature by developing ternary diagrams of relative expression. These findings are important in developing a more integrated systems approach by combining gene expression, ecophysiological influences and growth data to predict mycotoxin production. This could help in developing a more targeted approach to develop prevention strategies to control such carcinogenic natural metabolites that are prevalent in many staple food products. The model could also be used to predict the impact of climate change on toxin production.

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“…The temperature and relative humidity optimal for mycotoxin production may differ from those supporting fungal growth. 44 For example, in the field, the temperature range for A. flavus and A. parasiticus growth varies from 12-48°C (35-37°C optimum), and water activity requirement may be as low as 0.80 (0.95 optimum). However, aflatoxin production by these fungi requires a narrower range of temperature (28-33°C, 31°C optimum) and water activity (0.85-0.97; optimum 0.90).…”

Section: Discussionmentioning

confidence: 99%

“…After cessation of an active growth phase, fungi are known to produce numerous secondary metabolites, which are not required for growth of the fungus, 44 but have diverse functions and activities. Mycotoxins represent just a single subgroup of secondary metabolites; their structures as well as biological effects are numerous and have been the subject of many reviews.…”

Section: The Importance Of Secondary Fungal Metabolites: Mycotoxins Amentioning

confidence: 99%

Nonribosomal cyclic peptides: specific markers of fungal infections

Jegorov¹,

Hajdúch

Šulc

et al. 2006

J. Mass Spectrom.

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Some cyclic peptides and depsipeptides are synthesized in microorganisms by large multienzymes called nonribosomal peptide synthetases. The structures of peptide products originating in this way are complex and diverse and are microorganism-specific. This work proposes the use of fungal cyclic peptides and depsipeptides as extremely specific markers of fungal infections. Since a reliable molecular tool for diagnosing fungal infections at an early stage is still missing, we present mass spectrometry as a new, modern, broadband (with respect to fungal strain) and specific tool for clinical mycologists. More than 40 different fungal species can be rapidly characterized according to specific families of cyclic peptides, and in some cases, a particular fungal strain can be identified on the basis of its cyclopeptide profile. This paper is also aimed at initiating discussion on the biological role of these secondary metabolites, especially of those synthesized by medically important strains. Proven cytotoxic, anti-inflammatory or immunosuppressive activities of some cyclic peptides indicate that these molecules may contribute to the synergistic array of fungal virulence factors and support microbial invasion during fungal infection. In addition to an overview on recent mass spectrometric protocols for cyclic peptide sequencing, the structures of new peptides from Paecilomyces and Pseudallescheria are presented.

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Toxins of Filamentous Fungi

Cited by 142 publications

References 128 publications

The Tip Growth Apparatus ofAspergillus nidulans

The Tip Growth Apparatus ofAspergillus nidulans

A systems approach to model the relationship between aflatoxin gene cluster expression, environmental factors, growth and toxin production by Aspergillus flavus

Nonribosomal cyclic peptides: specific markers of fungal infections

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