A first insight into the genome of Prototheca wickerhamii, a major causative agent of human protothecosis

Abstract

Background Colourless microalgae of the Prototheca genus are the only known plants that have consistently been implicated in a range of clinically relevant opportunistic infections in both animals and humans. The Prototheca algae are emerging pathogens, whose incidence has increased importantly over the past two decades. Prototheca wickerhamii is a major human pathogen, responsible for at least 115 cases worldwide. Although the algae are receiving more attention nowadays, there is still a substantial knowledge gap regarding their biology, and pathogenicity in particular. Here we report, for the first time, the complete nuclear genome, organelle genomes, and transcriptome of the P. wickerhamii type strain ATCC 16529. Results The assembled genome size was of 16.7 Mbp, making it the smallest and most compact genome sequenced so far among the protothecans. Key features of the genome included a high overall GC content (64.5%), a high number (6081) and proportion (45.9%) of protein-coding genes, and a low repetitive sequence content (2.2%). The vast majority (90.6%) of the predicted genes were confirmed with the corresponding transcripts upon RNA-sequencing analysis. Most (93.2%) of the genes had their putative function assigned when searched against the InterProScan database. A fourth (23.3%) of the genes were annotated with an enzymatic activity possibly associated with the adaptation to the human host environment. The P. wickerhamii genome encoded a wide array of possible virulence factors, including those already identified in two model opportunistic fungal pathogens, i.e. Candida albicans and Trichophyton rubrum, and thought to be involved in invasion of the host or elicitation of the adaptive stress response. Approximately 6% of the P. wickerhamii genes matched a Pathogen-Host Interaction Database entry and had a previously experimentally proven role in the disease development. Furthermore, genes coding for proteins (e.g. ATPase, malate dehydrogenase) hitherto considered as potential virulence factors of Prototheca spp. were demonstrated in the P. wickerhamii genome. Conclusions Overall, this study is the first to describe the genetic make-up of P. wickerhamii and discovers proteins possibly involved in the development of protothecosis.

Genome Sequences of Two Strains of Prototheca wickerhamii Provide Insight Into the Protothecosis Evolution

“…A previous report described the chain of infection with, P. wickerhamii, namely the reservoirs, route of transmission and length of incubation, as unknown or variable (Khan et al, 2018). By 2017, at least 211 cases caused by P. wickerhamii had been reported (Bakula et al, 2021). In our laboratory, we have collected 59 Prototheca isolates from Chinese clinical patients coming from Shanghai, Beijing, Zhejiang, Sichuan, Jiangsu, Shandong, Jiangxi, Fujian, Guangxi, Guangdong, Yunnan, Chongqing, and Henan.…”

“…Until now, only little genomic data of Prototheca exist to support building this understanding. Five nuclear genome sequences are currently available in the NCBI database originating from five Prototheca species, namely, Prototheca ciferrii SAG2063 (Severgnini et al, 2018), Prototheca cutis JCM 15793 (Suzuki et al, 2018), Prototheca stagnora JCM 9641 (Suzuki et al, 2018), Prototheca bovis SAG 2021 (Severgnini et al, 2018), and P. wickerhamii ATCC 16529 (Bakula et al, 2021). However, all the public genomes (except for the one of P. wickerhamii) are draft genomes assembled from next-generation sequencing data, which limits the detailed genomic protothecosis research.…”

“…However, all the public genomes (except for the one of P. wickerhamii) are draft genomes assembled from next-generation sequencing data, which limits the detailed genomic protothecosis research. Using the first closed genome, Bakula et al could pioneer in describing the putative genes associated with protothecosis and disease development in P. wickerhamii (Bakula et al, 2021). Many genes associated with fungal pathogenicity, some potential virulence factors, and putative genes involved in protothecosis were identified in the P. wickerhamii genome (Bakula et al, 2021).…”

“…Using the first closed genome, Bakula et al could pioneer in describing the putative genes associated with protothecosis and disease development in P. wickerhamii (Bakula et al, 2021). Many genes associated with fungal pathogenicity, some potential virulence factors, and putative genes involved in protothecosis were identified in the P. wickerhamii genome (Bakula et al, 2021).…”

Prototheca-ID: a web-based application for molecular identification of Prototheca species

“…Our near-term priority would be to install within the Prototheca-ID application, a module for accommodating and filtering the whole-genome sequence datasets, representing all Prototheca species. The Prototheca whole-genome sequencing project, initiated by our group in 2014, has already released a complete sequence of the Prototheca wickerhamii genome ( 19 ).…”