The Small GTPase RacA Mediates Intracellular Reactive Oxygen Species Production, Polarized Growth, and Virulence in the Human Fungal Pathogen Aspergillus fumigatus

Li, Haiyan; Barker, Bridget M.; Grahl, Nora; Puttikamonkul, Srisombat; Bell, J.; Craven, Kelly D.; Cramer, Robert A.

doi:10.1128/ec.00288-10

Cited by 43 publications

(57 citation statements)

References 68 publications

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“…RacA, the homolog of RAC1, plays a crucial role in activation of Nox family NADPH oxidases by their interaction in both animals and fungi (651,(669)(670)(671)(672). ROS play a significant role in morphogenesis and in fungal plant colonization (673,674).…”

Section: Ras-gtpasesmentioning

confidence: 99%

The Genomes of Three Uneven Siblings: Footprints of the Lifestyles of Three Trichoderma Species

Schmoll

Dattenböck

Carreras-Villaseñor

et al. 2016

Microbiol Mol Biol Rev

163

195

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SUMMARYThe genusTrichodermacontains fungi with high relevance for humans, with applications in enzyme production for plant cell wall degradation and use in biocontrol. Here, we provide a broad, comprehensive overview of the genomic content of these species for “hot topic” research aspects, including CAZymes, transport, transcription factors, and development, along with a detailed analysis and annotation of less-studied topics, such as signal transduction, genome integrity, chromatin, photobiology, or lipid, sulfur, and nitrogen metabolism inT. reesei,T. atroviride, andT. virens, and we open up new perspectives to those topics discussed previously. In total, we covered more than 2,000 of the predicted 9,000 to 11,000 genes of eachTrichodermaspecies discussed, which is >20% of the respective gene content. Additionally, we considered available transcriptome data for the annotated genes. Highlights of our analyses include overall carbohydrate cleavage preferences due to the different genomic contents and regulation of the respective genes. We found light regulation of many sulfur metabolic genes. Additionally, a new Golgi 1,2-mannosidase likely involved inN-linked glycosylation was detected, as were indications for the ability ofTrichodermaspp. to generate hybrid galactose-containingN-linked glycans. The genomic inventory of effector proteins revealed numerous compounds unique toTrichoderma, and these warrant further investigation. We found interesting expansions in theTrichodermagenus in several signaling pathways, such as G-protein-coupled receptors, RAS GTPases, and casein kinases. A particularly interesting feature absolutely unique toT. atrovirideis the duplication of the alternative sulfur amino acid synthesis pathway.

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Section: Ras-gtpasesmentioning

confidence: 99%

The Genomes of Three Uneven Siblings: Footprints of the Lifestyles of Three Trichoderma Species

Schmoll

Dattenböck

Carreras-Villaseñor

et al. 2016

Microbiol Mol Biol Rev

163

195

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“…(Andrejko et al, 2009;Coleman et al, 2011;Desbois & Coote, 2012;Dunphy et al, 1986;Evans & Rozen, 2012;Fallon et al, 2011;Fuchs et al, 2010;Harding et al, 2012;Harrison et al, 2006;Joyce & Gahan, 2010;Lebreton et al, 2011;Leuko & Raivio, 2012;Mesa-Arango et al, 2013;Miyata et al, 2003;Mylonakis et al, 2005;Mukherjee et al, 2010;Peleg et al, 2009;Scully & Bidochka, 2009;Soukup et al, 2012). Moreover, virulence in these larvae has in many instances been shown to be similar to that in mammals, and to involve similar pathogenicity and virulence determinants (Brennan et al, 2002;Cook & McArthur, 2013;Dunphy et al, 2003;Fuchs & Mylonakis, 2006;Jander et al, 2000;Mukherjee et al, 2010;Wand et al, 2011), including for A. fumigatus (Amich et al, 2013;Jackson et al, 2009;Li et al, 2011;O'Hanlon et al, 2011;Slater et al, 2011;Soukup et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Genetic and virulence variation in an environmental population of the opportunistic pathogen Aspergillus fumigatus

Alshareef

Robson

2014

Microbiology

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Environmental populations of the opportunistic pathogen Aspergillus fumigatus have been shown to be genotypically diverse and to contain a range of isolates with varying pathogenic potential. In this study, we combined two RAPD primers to investigate the genetic diversity of environmental isolates from Manchester collected monthly over 1 year alongside Dublin environmental isolates and clinical isolates from patients. RAPD analysis revealed a diverse genotype, but with three major clinical isolate clusters. When the pathogenicity of clinical and Dublin isolates was compared with a random selection of Manchester isolates in a Galleria mellonella larvae model, as a group, clinical isolates were significantly more pathogenic than environmental isolates. Moreover, when relative pathogenicity of individual isolates was compared, clinical isolates were the most pathogenic, Dublin isolates were the least pathogenic and Manchester isolates showed a range in pathogenicity. Overall, this suggests that the environmental population is genetically diverse, displaying a range in pathogenicity, and that the most pathogenic strains from the environment are selected during patient infection. INTRODUCTIONAspergillus fumigatus is an opportunistic fungal pathogen that can cause aspergillosis in immunocompromised patients, such as those with neutropenia or on immunosuppressive therapy following solid organ transplantation (Abad et al., 2010;Ben-Ami et al., 2010;Dagenais & Keller, 2009;Latgé, 1999;Rementeria et al., 2005). The principal route of infection is through the inhalation of airborne spores, which due to their small spore size are able to reach the alveoli (Dagenais & Keller, 2009;Ibrahim-Granet et al., 2003;Latgé, 1999;O'Gorman, 2011;Philippe et al., 2003). While other aspergilli can cause opportunistic infections (such as Aspergillus terreus and Aspergillus flavus), A. fumigatus accounts for~90 % of all cases despite airborne spore numbers only accounting for ,1 % of all Aspergillus spores (Rementeria et al., 2005). A number of studies have shown a high degree of genetic variation within the A. fumigatus population, and whilst some studies have indicated potential geographical subgroups, comparisons between clinical isolates and environmental isolates have largely been unable to distinguish these populations (Araujo et al., 2010;Aufauvre-Brown et al., 1992;Balajee et al., 2008;Chazalet et al., 1998;Denning et al., 1990;Duarte-Escalante et al., 2009; Leenders et al., 1999;Menotti et al., 2005). Moreover, epidemiological studies have largely failed to match genotypes in infected patients with genotypes found in hospitals, in part due to the high level of genetic diversity in the environmental populations (Araujo et al., 2010;Bart-Delabesse et al., 1999;Chazalet et al., 1998;Guinea et al., 2011; Leenders et al., 1999;de Valk et al., 2007), and similar findings have been reported in avian populations (Arné et al., 2011;Lair-Fulleringer et al., 2003;Olias et al., 2011). Whilst genotyping of isolates from some individual patient...

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“…In Magnaporthe oryzae, Rac1 is necessary for conidial formation and contributes to pathogenicity, since strains expressing CA-Rac display defects in infection-related growth (10). Deletion of Rac1 in Aspergillus fumigatus results in a reduced growth rate and abnormal conidial formation; however, it does not affect virulence (25). In Candida albicans, Rac1 is not necessary for viability or serum-induced hyphal growth, but it is essential for filamentous growth when cells are embedded in a matrix (3).…”

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confidence: 99%

Regulation of Pathogenic Spore Germination by CgRac1 in the Fungal Plant Pathogen Colletotrichum gloeosporioides

Nesher

Minz

Kokkelink³

et al. 2011

Eukaryot Cell

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Colletotrichum gloeosporioides is a facultative plant pathogen: it can live as a saprophyte on dead organic matter or as a pathogen on a host plant. Different patterns of conidial germination have been recognized under saprophytic and pathogenic conditions, which also determine later development. Here we describe the role of CgRac1 in regulating pathogenic germination. The hallmark of pathogenic germination is unilateral formation of a single germ tube following the first cell division. However, transgenic strains expressing a constitutively active CgRac1 (CA-CgRac1) displayed simultaneous formation of two germ tubes, with nuclei continuing to divide in both cells after the first cell division. CA-CgRac1 also caused various other abnormalities, including difficulties in establishing and maintaining cell polarity, reduced conidial and hyphal adhesion, and formation of immature appressoria. Consequently, CA-CgRac1 isolates were completely nonpathogenic. Localization studies with cyan fluorescent protein (CFP)-CgRac1 fusion protein showed that the CgRac1 protein is abundant in conidia and in hyphal tips. Although the CFP signal was equally distributed in both cells of a germinating conidium, reactive oxygen species accumulated only in the cell that produced a germ tube, indicating that CgRac1 was active only in the germinating cell. Collectively, our results show that CgRac1 is a major regulator of asymmetric development and that it is involved in the regulation of both morphogenesis and nuclear division. Modification of CgRac1 activity disrupts the morphogenetic program and prevents fungal infection.

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The Small GTPase RacA Mediates Intracellular Reactive Oxygen Species Production, Polarized Growth, and Virulence in the Human Fungal Pathogen Aspergillus fumigatus

Cited by 43 publications

References 68 publications

The Genomes of Three Uneven Siblings: Footprints of the Lifestyles of Three Trichoderma Species

The Genomes of Three Uneven Siblings: Footprints of the Lifestyles of Three Trichoderma Species

Genetic and virulence variation in an environmental population of the opportunistic pathogen Aspergillus fumigatus

Regulation of Pathogenic Spore Germination by CgRac1 in the Fungal Plant Pathogen Colletotrichum gloeosporioides

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