Apophysomyces variabilis: draft genome sequence and comparison of predictive virulence determinants with other medically important Mucorales

Abstract

Background Apophysomyces species are prevalent in tropical countries and A. variabilis is the second most frequent agent causing mucormycosis in India. Among Apophysomyces species, A. elegans, A. trapeziformis and A. variabilis are commonly incriminated in human infections. The genome sequences of A. elegans and A. trapeziformis are available in public database, but not A. variabilis. We, therefore, performed the whole genome sequence of A. variabilis to explore its genomic structure and possible genes determining the virulence of the organism.ResultsThe whole genome of A. variabilis NCCPF 102052 was sequenced and the genomic structure of A. variabilis was compared with already available genome structures of A. elegans, A. trapeziformis and other medically important Mucorales. The total size of genome assembly of A. variabilis was 39.38 Mb with 12,764 protein-coding genes. The transposable elements (TEs) were low in Apophysomyces genome and the retrotransposon Ty3-gypsy was the common TE. Phylogenetically, Apophysomyces species were grouped closely with Phycomyces blakesleeanus. OrthoMCL analysis revealed 3025 orthologues proteins, which were common in those three pathogenic Apophysomyces species. Expansion of multiple gene families/duplication was observed in Apophysomyces genomes. Approximately 6% of Apophysomyces genes were predicted to be associated with virulence on PHIbase analysis. The virulence determinants included the protein families of CotH proteins (invasins), proteases, iron utilisation pathways, siderophores and signal transduction pathways. Serine proteases were the major group of proteases found in all Apophysomyces genomes. The carbohydrate active enzymes (CAZymes) constitute the majority of the secretory proteins.ConclusionThe present study is the maiden attempt to sequence and analyze the genomic structure of A. variabilis. Together with available genome sequence of A. elegans and A. trapeziformis, the study helped to indicate the possible virulence determinants of pathogenic Apophysomyces species. The presence of unique CAZymes in cell wall might be exploited in future for antifungal drug development.Electronic supplementary materialThe online version of this article (10.1186/s12864-017-4136-1) contains supplementary material, which is available to authorized users.

Understanding Mucormycoses in the Age of “omics”

“…Rather, the duplicative nature of the L. corymbifera genome appears to be mediated by the high occurrence of tandem duplications (Schwartze et al, 2014). This pattern was also observed in whole genome sequencing and comparison of Apophysomyces species, which demonstrated extensive gene duplication and expansion across its genome but no evidence of a WGD (Prakash et al, 2017).…”

“…Additionally, there is wide variety in the structure of the mating type locus within Rhizopus genomes that vary from typical arrangements seen in Mucoralean fungi (Gryganskyi et al, 2018). Similar to L. corymbifera (Schwartze et al, 2014), Apophysomyces species had a lower number of transposable elements (TEs) in their genome when compared to other Mucorales species (Prakash et al, 2017). Both cases were associated with multiple copies of heterokaryon incompatibility (HET) genes and genes associated with RNA interference (RNAi) pathway (Schwartze et al, 2014;Prakash et al, 2017).…”

“…The R. delemar genome contains nearly double the number of chitin synthases (CHS) and chitin deacetylases (CDA) encoding genes of other dikaryotic fungi (Ma et al, 2009). The expansions of the CHS-and CDA-encoding genes were also demonstrated in the genomes of 29 additional Mucorales species across 10 genera (Chibucos et al, 2016;Corrochano et al, 2016;Prakash et al, 2017). Genomic and transcriptomic studies have elucidated different ways in which Mucorales maintains and changes cell wall integrity.…”

“…The identification of these genes by transcriptome analysis could allow researchers to target germination of R. delemar and prevent invasive mucormycosis. The genomes of Apophysomyces species show a unique profile of carbohydrate active enzymes (CAZymes) responsible for the generation of Apophysomyces cell wall polysaccharides, which may represent a novel antifungal target (Prakash et al, 2017). Difference patterns in CAZymes repertoire was also observed in the genomes of Mucor species that differed in lifestyle (Lebreton et al, 2020).…”

“…One recent study claims that Apophysomyces spp. based on the examination of 3 genomes, have >15 copies of CotH-like genes (Prakash et al, 2017). The discordant estimation of CotH-like gene copy number in Apophysomyces spp.…”