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

Abstract

The Prototheca alga is the only chlorophyte known to be involved in a series of clinically relevant opportunistic infections in humans and animals, namely, protothecosis. Most pathogenic cases in humans are caused by Prototheca wickerhamii. In order to investigate the evolution of Prototheca and the genetic basis for its pathogenicity, the genomes of two P. wickerhamii strains S1 and S931 were sequenced using Nanopore long-read and Illumina short-read technologies. The mitochondrial, plastid, and nuclear genomes were assembled and annotated including a transcriptomic data set. The assembled nuclear genome size was 17.57 Mb with 19 contigs and 17.45 Mb with 26 contigs for strains S1 and S931, respectively. The number of predicted protein-coding genes was approximately 5,700, and more than 96% of the genes could be annotated with a gene function. A total of 2,798 gene families were shared between the five currently available Prototheca genomes. According to the phylogenetic analysis, the genus of Prototheca was classified in the same clade with A. protothecoides and diverged from Chlorella ~500 million years ago (Mya). A total of 134 expanded genes were enriched in several pathways, mostly in metabolic pathways, followed by biosynthesis of secondary metabolites and RNA transport. Comparative analysis demonstrated more than 96% consistency between the two herein sequenced strains. At present, due to the lack of sufficient understanding of the Prototheca biology and pathogenicity, the diagnosis rate of protothecosis is much lower than the actual infection rate. This study provides an in-depth insight into the genome sequences of two strains of P. wickerhamii isolated from the clinic to contribute to the basic understanding of this alga and explore future prevention and treatment strategies.

Integration of transcriptomics, proteomics, and metabolomics data for the detection of the human pathogenic Prototheca wickerhamii from a One Health perspective

“…This was also true for the DEPs and metabolites (Figure 2A). This is consistent with previous results showing that strains HN01 and ATCC16529 evolved closely (Guo et al, 2022). Interestingly, we found that mannan endo-1,4-b-mannosidase was significantly downregulated in S1 compared to that in HN01 (Figure 2B).…”

“…Moreover, higher temperatures combined with high humidity would enhance the growth of P. wickerhamii in the environment (Jagielski et al, 2022). This study provides an indepth understanding of the genome sequences of different strains of P. wickerhamii isolated from clinical specimens, contributes to a basic understanding of this alga, and explores future prevention and treatment strategies (Guo et al, 2022).…”

“…CaTUP1 and Tup1 are related to transcription factors and inhibitors, respectively. Therefore, transcriptional regulation may be important in the pathogenesis of human protothecosis (Guo et al, 2022). Of the 245 proteins identified in Prototheca zopfii from the iTRAQ-LC-MS/MS proteomic analysis, only 22 proteins were clearly identified, most of which were putative uncharacterised proteins (Liu et al, 2018).…”

“…Expanding knowledge based on genome sequencing (Bakuła et al, 2021;Guo et al, 2022) and transcriptomic, proteomic, and metabolomic analyses of P. wickerhamii may contribute to a better understanding of the pathways of infection and pathogenesis. The Prototheca cell wall is a complex structure composed primarily of bglucan and mannan.…”

Insights from comparative plastid genomics of colorless facultative pathogensPrototheca(Chlorophyta): Unveiling membrane transport and organelle division as key functions

“…Close relatedness between organisms exhibiting vastly different lifestyles is often a hallmark of complex and captivating evolutionary paths, and a perfect example of that can be found among the green algal order Chlorellales. The relatives of the model green microalga Chlorella include a photosynthetic genus Auxenochlorella, as well as two secondarily non-photosynthetic genera -Helicosporidium, which are highly specialized, obligate gut parasites of insects (de Koning and Keeling, 2006;De Koning and Keeling, 2004;Sun and Pombert, 2014;Tartar, 2013), and Prototheca, which are predominantly free-living opportunistic pathogens of diverse vertebrates, including humans (Borza et al, 2005;Guo et al, 2022;Jagielski et al, 2019Jagielski et al, , 2018. The evolutionary past of these organisms, especially their transitions between photosynthetic, parasitic and free-living heterotrophic lifestyles, remains mysterious even with the availability of several genomic datasets.…”