Fungal model systems and the elucidation of pathogenicity determinants

Pérez‐Nadales, Elena; Nogueira, Filomena; Baldin, Clara; Castanheira, Sónia; Ghalid, Mennat El; Grund, Elisabeth; Lengeler, Klaus B.; Marchegiani, Elisabetta; Mehrotra, Pankaj; Moretti, Marino; Naik, Vikram; Osés-Ruiz, Míriam; Oskarsson, Therese; Schäfer, Katja; Wasserstrom, Lisa; Brakhage, Axel A.; Gow, Neil A. R.; Kahmann, Regine; Lebrun, Marc; Perez-Martin, J.; Pietro, Antonio Di; Talbot, Nicholas J.; Toquin, Valérie; Walther, Andrea; Wendland, Jürgen

doi:10.1016/j.fgb.2014.06.011

Cited by 146 publications

(104 citation statements)

References 239 publications

(298 reference statements)

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“…Fungal pathogens have evolved a variety of strategies for successful infection of target hosts (47,48). Fungal spores (conidia) of the insect pathogenic fungus, B. bassiana, will attempt to attach and initiate infection essentially anywhere on host cuticle, although preferential infection sites on some hosts have been observed (21,49,50).…”

Section: Discussionmentioning

confidence: 99%

Tenebrionid secretions and a fungal benzoquinone oxidoreductase form competing components of an arms race between a host and pathogen

Pedrini

Ortiz‐Urquiza

Huarte‐Bonnet

et al. 2015

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

123

118

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Entomopathogenic fungi and their insect hosts represent a model system for examining invertebrate-pathogen coevolutionary selection processes. Here we report the characterization of competing components of an arms race consisting of insect protective antimicrobial compounds and evolving fungal mechanisms of detoxification. The insect pathogenic fungus Beauveria bassiana has a remarkably wide host range; however, some insects are resistant to fungal infection. Among resistant insects is the tenebrionid beetle Tribolium castaneum that produces benzoquinone-containing defensive secretions. Reduced fungal germination and growth was seen in media containing T. castaneum dichloromethane extracts or synthetic benzoquinone. In response to benzoquinone exposure, the fungus expresses a 1,4-benzoquinone oxidoreductase, BbbqrA, induced >40-fold. Gene knockout mutants (ΔBbbqrA) showed increased growth inhibition, whereas B. bassiana overexpressing BbbqrA (Bb::BbbqrAO) displayed increased resistance to benzoquinone compared with wild type. Increased benzoquinone reductase activity was detected in wild-type cells exposed to benzoquinone and in the overexpression strain. Heterologous expression and purification of BbBqrA in Escherichia coli confirmed NAD(P)H-dependent benzoquinone reductase activity. The ΔBbbqrA strain showed decreased virulence toward T. castaneum, whereas overexpression of BbbqrA increased mortality versus T. castaneum. No change in virulence was seen for the ΔBbbqrA or Bb::BbbqrAO strains when tested against the greater wax moth Galleria mellonella or the beetle Sitophilus oryzae, neither of which produce significant amounts of cuticular quinones. The observation that artificial overexpression of BbbqrA results in increased virulence only toward quinone-secreting insects implies the lack of strong selection or current failure of B. bassiana to counteradapt to this particular host defense throughout evolution.

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Section: Discussionmentioning

confidence: 99%

Tenebrionid secretions and a fungal benzoquinone oxidoreductase form competing components of an arms race between a host and pathogen

Pedrini

Ortiz‐Urquiza

Huarte‐Bonnet

et al. 2015

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

123

118

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“…gossypii is one of the simplest filamentous fungal species studied, which due to its close relationship to yeast, small genome size and easy genetic manipulation arose as an attractive model to study fungal developmental biology (reviewed in Perez-Nadales et al, 2014;Schmitz and Philippsen, 2011;Wendland and Walther, 2005). Its life cycle (Fig.…”

Section: Life Cyclementioning

confidence: 99%

“…Industrially exploited for more than 20 years due to its natural ability to overproduce riboflavin, A. gossypii is considered a remarkable example of the sustainable white biotechnology business model (Kato and Park, 2012;Lim et al, 2001;Stahmann et al, 2000;zu Berstenhorst et al, 2009). Nevertheless, the scientific prominence of A. gossypii is not limited to its biotechnological potential, since it is also extensively used as a model organism in fungal developmental and evolutionary biology studies (Perez-Nadales et al, 2014;Schmitz and Philippsen, 2011;Wendland and Walther, 2005). Its industrial relevance and the basic knowledge accumulated along the years promoted the development of molecular and in silico tools that, in turn, have allowed the continuous engineering of A. gossypii strains with improved riboflavin production traits, either through random or rational approaches.…”

Section: Introductionmentioning

confidence: 99%

Ashbya gossypii beyond industrial riboflavin production: A historical perspective and emerging biotechnological applications

Aguiar

Silva

Domingues

2015

Biotechnology Advances

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The filamentous fungus Ashbya gossypii has been safely and successfully used for more than two decades in the commercial production of riboflavin (vitamin B2). Its industrial relevance combined with its high genetic similarity with Saccharomyces cerevisiae together promoted the accumulation of fundamental knowledge that has been efficiently converted into a significant molecular and in silico toolbox for its genetic engineering. This synergy has enabled a directed and sustained exploitation of A. gossypii as an industrial riboflavin producer. Although there is still room for optimizing riboflavin production, the recent years have seen an abundant advance in the exploration of A. gossypii for other biotechnological applications, such as the production of recombinant proteins, single cell oil and flavour compounds. Here, we will address the biotechnological potential of A. gossypii beyond riboflavin production by presenting (a) a physiological and metabolic perspective over this fungus; (b) the molecular toolbox available for its manipulation; and (c) commercial and emerging biotechnological applications for this industrially important fungus, together with the approaches adopted for its engineering.

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“…Immunocompromised patients can acquire IA through the inhalation of conidia that invade the pulmonary alveoli, translocating into the blood and subsequently disseminating to other organs and niches throughout the human body. Aspergillus fumigatus is the main causal agent of aspergillosis (1,2), causing around 65% of all Aspergillus invasive infections, and is the most encountered species in pulmonary infections (3)(4)(5). Aspergillosis is a multifactorial disease, with several phenotypes influencing the final outcome of the disease.…”

mentioning

confidence: 99%

The Aspergillus fumigatus sitA Phosphatase Homologue Is Important for Adhesion, Cell Wall Integrity, Biofilm Formation, and Virulence

et al. 2015

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h Aspergillus fumigatus is an opportunistic pathogenic fungus able to infect immunocompromised patients, eventually causing disseminated infections that are difficult to control and lead to high mortality rates. It is important to understand how the signaling pathways that regulate these factors involved in virulence are orchestrated. Protein phosphatases are central to numerous signal transduction pathways. Here, we characterize the A. fumigatus protein phosphatase 2A SitA, the Saccharomyces cerevisiae Sit4p homologue. The sitA gene is not an essential gene, and we were able to construct an A. fumigatus null mutant. The ⌬sitA strain had decreased MpkA phosphorylation levels, was more sensitive to cell wall-damaging agents, had increased ␤-(1,3)-glucan and chitin, was impaired in biofilm formation, and had decreased protein kinase C activity. The ⌬sitA strain is more sensitive to several metals and ions, such as MnCl 2 , CaCl 2 , and LiCl, but it is more resistant to ZnSO 4 . The ⌬sitA strain was avirulent in a murine model of invasive pulmonary aspergillosis and induces an augmented tumor necrosis factor alpha (TNF-␣) response in mouse macrophages. These results stress the importance of A. fumigatus SitA as a possible modulator of PkcA/MpkA activity and its involvement in the cell wall integrity pathway.

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Fungal model systems and the elucidation of pathogenicity determinants

Cited by 146 publications

References 239 publications

Tenebrionid secretions and a fungal benzoquinone oxidoreductase form competing components of an arms race between a host and pathogen

Tenebrionid secretions and a fungal benzoquinone oxidoreductase form competing components of an arms race between a host and pathogen

Ashbya gossypii beyond industrial riboflavin production: A historical perspective and emerging biotechnological applications

The Aspergillus fumigatus sitA Phosphatase Homologue Is Important for Adhesion, Cell Wall Integrity, Biofilm Formation, and Virulence

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