Dataset Information

The mitochondrial genome of the sooty swift (Cypseloides fumigatus).

ABSTRACT: We assembled the mitogenome of Cypseloides fumigatus based on off-target sequences from ultraconserved elements sequencing. We found a total length of 16,850?bp, including 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and one control region, organized in the standard avian gene order. We have built a phylogenetic tree including 26 species of swifts that suggested C. fumigatus as sister species of C. cryptus, and indicated exciting opportunities for biogeographic inferences involving most continents, including Neartic vs Neotropical disjunctions and local radiations across the globe. Finally, we found cases of lack of reciprocal monophyly between named species and high intra-specific divergence, suggesting that population-level studies are warranted.

SUBMITTER: Biancalana RN

PROVIDER: S-EPMC7800099 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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The mitochondrial genome of the sooty swift (Cypseloides fumigatus).

Biancalana Renata Neves RN Biondo Cibele C Raposo do Amaral Fabio F

Mitochondrial DNA. Part B, Resources 20170405 1

We assembled the mitogenome of Cypseloides fumigatus based on off-target sequences from ultraconserved elements sequencing. We found a total length of 16,850 bp, including 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and one control region, organized in the standard avian gene order. We have built a phylogenetic tree including 26 species of swifts that suggested C. fumigatus as sister species of C. cryptus, and indicated exciting opportunities for biogeographic infe ...[more]

PMID: 33473767

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Project description:Ergosterol plays an important role in maintaining cell membrane sterol homeostasis in fungi, and as such, it is considered an effective target in antifungal chemotherapy. In yeast, the enzyme acetyl-coenzyme A (CoA) acetyltransferase (ERG10) catalyzes the Claisen condensation of two acetyl-CoA molecules to acetoacetyl-CoA in the ergosterol biosynthesis pathway and is reported as being critical for cell viability. Using yeast ERG10 for alignment, two orthologues, AfERG10A (AFUB_000550) and AfERG10B (AFUB_083570), were discovered in the opportunistic fungal pathogen Aspergillus fumigatus Despite the essentiality of AfERG10B having been previously validated, the biological function of AfERG10A remains unclear. In this study, we have characterized recombinant AfERG10A as a functional acetyl-CoA acetyltransferase catalyzing both synthetic and degradative reactions. Unexpectedly, AfERG10A localizes to the mitochondria in A. fumigatus, as shown by C-terminal green fluorescent protein (GFP) tag fusion. Both knockout and inducible promoter strategies demonstrate that Aferg10A is essential for the survival of A. fumigatus The reduced expression of Aferg10A leads to severe morphological defects and increased susceptibility to oxidative and cell wall stresses. Although the catalytic mechanism of acetyl-CoA acetyltransferase family is highly conserved, the crystal structure of AfERG10A and its complex with CoA are solved, revealing four substitutions within the CoA binding site that are different from human orthologues. Taken together, our combination of genetic and structural studies demonstrates that mitochondrial AfERG10A is essential for A. fumigatus cell viability and could be a potential drug target to feed the antifungal drug development pipeline.IMPORTANCE A growing number of people worldwide are suffering from invasive aspergillosis caused by the human opportunistic fungal pathogen A. fumigatus Current therapeutic options rely on a limited repertoire of antifungals. Ergosterol is an essential component of the fungal cell membrane as well as a target of current antifungals. Approximately 20 enzymes are involved in ergosterol biosynthesis, of which acetyl-CoA acetyltransferase (ACAT) is the first enzyme. Two ACATs in A. fumigatus are AfErg10A and AfErg10B. However, the biological function of AfErg10A is yet to be investigated. In this study, we showed that AfErg10A is localized in the mitochondria and is essential for A. fumigatus survival and morphological development. In combination with structural studies, we validated AfErg10A as a potential drug target that will facilitate the development of novel antifungals and improve the efficiency of existing drugs.

Dataset Information

The mitochondrial genome of the sooty swift (Cypseloides fumigatus).

Publications

The mitochondrial genome of the sooty swift (<i>Cypseloides fumigatus</i>).

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