Abstract:MgtC is important for the survival of several bacterial pathogens in macrophages and for growth under magnesium limitation. Among eukaryotes, a gene homologous to mgtC was found only in the pathogenic fungus Aspergillus fumigatus. Our data show that the A. fumigatus MgtC (AfuMgtC) protein does not have the same function as the bacterial MgtC proteins.
“…A eukaryotic homolog was found in A. fumigatus, but this MgtC homolog is not involved in magnesium metabolism and has no function in fungal virulence. It only suggests that horizontal transfer of bacterial genes can occur in A. fumigatus (388). This is another example of the necessity to be careful in considering in silico homologies and annotations.…”
Section: Acquiring Foodmentioning
confidence: 99%
“…The presence of these viruses may have a role in fungal virulence, since the sequenced strain Af293, which is infected with a mycovirus, is less pathogenic than other wild-type strains (176). In addition to biochemical interactions, the presence of viruses and horizontal gene transfer events (388) suggest the exchange of genetic material between members of the microbiota. Finally, association of Aspergillus conidia with environmental nanoparticles modulates host response and virulence and deserves further research (594).…”
Section: Some Unexplored Biological Features Of a Fumigatusmentioning
SUMMARY
Aspergillus fumigatus is a saprotrophic fungus; its primary habitat is the soil. In its ecological niche, the fungus has learned how to adapt and proliferate in hostile environments. This capacity has helped the fungus to resist and survive against human host defenses and, further, to be responsible for one of the most devastating lung infections in terms of morbidity and mortality. In this review, we will provide (i) a description of the biological cycle of A. fumigatus; (ii) a historical perspective of the spectrum of aspergillus disease and the current epidemiological status of these infections; (iii) an analysis of the modes of immune response against Aspergillus in immunocompetent and immunocompromised patients; (iv) an understanding of the pathways responsible for fungal virulence and their host molecular targets, with a specific focus on the cell wall; (v) the current status of the diagnosis of different clinical syndromes; and (vi) an overview of the available antifungal armamentarium and the therapeutic strategies in the clinical context. In addition, the emergence of new concepts, such as nutritional immunity and the integration and rewiring of multiple fungal metabolic activities occurring during lung invasion, has helped us to redefine the opportunistic pathogenesis of A. fumigatus.
“…A eukaryotic homolog was found in A. fumigatus, but this MgtC homolog is not involved in magnesium metabolism and has no function in fungal virulence. It only suggests that horizontal transfer of bacterial genes can occur in A. fumigatus (388). This is another example of the necessity to be careful in considering in silico homologies and annotations.…”
Section: Acquiring Foodmentioning
confidence: 99%
“…The presence of these viruses may have a role in fungal virulence, since the sequenced strain Af293, which is infected with a mycovirus, is less pathogenic than other wild-type strains (176). In addition to biochemical interactions, the presence of viruses and horizontal gene transfer events (388) suggest the exchange of genetic material between members of the microbiota. Finally, association of Aspergillus conidia with environmental nanoparticles modulates host response and virulence and deserves further research (594).…”
Section: Some Unexplored Biological Features Of a Fumigatusmentioning
SUMMARY
Aspergillus fumigatus is a saprotrophic fungus; its primary habitat is the soil. In its ecological niche, the fungus has learned how to adapt and proliferate in hostile environments. This capacity has helped the fungus to resist and survive against human host defenses and, further, to be responsible for one of the most devastating lung infections in terms of morbidity and mortality. In this review, we will provide (i) a description of the biological cycle of A. fumigatus; (ii) a historical perspective of the spectrum of aspergillus disease and the current epidemiological status of these infections; (iii) an analysis of the modes of immune response against Aspergillus in immunocompetent and immunocompromised patients; (iv) an understanding of the pathways responsible for fungal virulence and their host molecular targets, with a specific focus on the cell wall; (v) the current status of the diagnosis of different clinical syndromes; and (vi) an overview of the available antifungal armamentarium and the therapeutic strategies in the clinical context. In addition, the emergence of new concepts, such as nutritional immunity and the integration and rewiring of multiple fungal metabolic activities occurring during lung invasion, has helped us to redefine the opportunistic pathogenesis of A. fumigatus.
“…Therefore, HGT has also played a significant role in distributing genes in eukaryotes. In addition to the individual gene studies [ 7 , 8 , 9 ], large-scale, genome-wide HGT studies in eukaryotes have also been published and recently summarized in a few review articles [ 10 , 11 , 12 , 13 ].…”
Section: Introductionmentioning
confidence: 99%
“…Fungi are the most researched eukaryotes that have been surveyed for HGT, probably because they have the most sequenced genomes (more than 500 complete/draft genomes so far). Numerous cases of HGTs have been reported including some genome-wide detection of fungi-fungi and fungi-bacteria gene transfers [ 7 , 8 , 9 , 14 , 15 , 16 , 17 , 18 , 19 ]. One of the most interesting findings made in these studies is that genes are often transferred as physically linked gene clusters, many of which encode enzymes of the secondary/specialized metabolic pathways.…”
Horizontal gene transfer (HGT) is a fast-track mechanism that allows genetically unrelated organisms to exchange genes for rapid environmental adaptation. We developed a new phyletic distribution-based software, HGT-Finder, which implements a novel bioinformatics algorithm to calculate a horizontal transfer index and a probability value for each query gene. Applying this new tool to the Aspergillus fumigatus, Aspergillus flavus, and Aspergillus nidulans genomes, we found 273, 542, and 715 transferred genes (HTGs), respectively. HTGs have shorter length, higher guanine-cytosine (GC) content, and relaxed selection pressure. Metabolic process and secondary metabolism functions are significantly enriched in HTGs. Gene clustering analysis showed that 61%, 41% and 74% of HTGs in the three genomes form physically linked gene clusters (HTGCs). Overlapping manually curated, secondary metabolite gene clusters (SMGCs) with HTGCs found that 9 of the 33 A. fumigatus SMGCs and 31 of the 65 A. nidulans SMGCs share genes with HTGCs, and that HTGs are significantly enriched in SMGCs. Our genome-wide analysis thus presented very strong evidence to support the hypothesis that HGT has played a very critical role in the evolution of SMGCs. The program is freely available at .
“…S3). Most of the down-regulated genes were those encoding hypothetical proteins (Table 2), including the MgtC/SapB family membrane protein which are homologous to a bacterial virulence factor but their function was still not known 25 .Figure 7Genome-wide expression analyses of the Δ rgsD mutant and WT. ( A ) Linear fitted model showing the correlation between overall gene expression for WT and Δ gprK strains.…”
The regulator of G protein signaling (RGS) domain proteins generally attenuate heterotrimeric G protein signaling, thereby fine-tune the duration and strength of signal transduction. In this study, we characterize the functions of RgsD, one of the six RGS domain proteins present in the human pathogenic fungus Aspergillus fumigatus. The deletion (Δ) of rgsD results in enhanced asexual sporulation coupled with increased mRNA levels of key developmental activators. Moreover, ΔrgsD leads to increased spore tolerance to UV and oxidative stress, which might be associated with the enhanced expression of melanin biosynthetic genes and increased amount of melanin. Yeast two-hybrid assays reveal that RgsD can interact with the three Gα proteins GpaB, GanA, and GpaA, showing the highest interaction potential with GpaB. Importantly, the ΔrgsD mutant shows elevated expression of genes in the cAMP-dependent protein kinase A (PKA) pathway and PKA catalytic activity. The ΔrgsD mutant also display increased gliotoxin production and elevated virulence toward Galleria mellonella wax moth larvae. Transcriptomic analyses using RNA-seq reveal the expression changes associated with the diverse phenotypic outcomes caused by ΔrgsD. Collectively, we conclude that RgsD attenuates cAMP-PKA signaling pathway and negatively regulates asexual development, toxigenesis, melanin production, and virulence in A. fumigatus.
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