Protothecosis, an infrequent human infection, is caused by achlorophyllic algae belonging to the genus Prototheca, particularly Prototheca wickerhamii. The skin stands as the most commonly affected organ. This report documents a case involving an 82-year-old male with Protothecosis. Histopathological analysis revealed granulomatous inflammation in the dermis, exhibiting necrotic features and hosting numerous non-budding spherical organisms. These organisms were positively stained using methenamine silver and periodic acid-Schiff stains, confirming identification as P. wickerhamii after validation through tissue culture and sequencing procedures. Initially, the patient received oral itraconazole at a dosage of 200 mg daily, accompanied by topical 1% naftifine-0.25% ketoconazole cream for a duration of 4 weeks, resulting in significant improvement. Subsequently, due to gastrointestinal discomfort presumably linked to itraconazole, terbinafine was administered. Over a span of 3 months, the patient received oral terbinafine at a dosage of 250 mg/day alongside the application of topical 1% naftifine-0.25% ketoconazole cream, leading to complete healing of the skin lesion, leaving behind a fibrotic scar.

Prototheca is a microalgae known to cause infections in humans, with protothecosis most commonly presenting as olecranon bursitis or localized soft tissue infection. Disseminated disease can be seen in immunocompromised patients. In this retrospective single-institution case series, we describe our experience with 7 patients with Prototheca infections.

Prototheca species are the only microalgae known to cause opportunistic infections in vertebrates and humans. Most cases of protothecosis in humans are caused by Prototheca wickerhamii, but knowledge of the pathogenicity and biology of Prototheca is limited. Globally, the diagnostic rate of Prototheca species infection is much lower than the actual rate of P. wickerhamii. The precise mechanisms underlying the pathogenesis of Prototheca infections remain unclear. In this study, we identified a strain of P. wickerhamii with atypical colony morphology. To reveal the morphological differences between P. wickerhamii S1 (mucous) and the molecular basis of its pathogenicity, the transcriptomics, proteomics, and metabolomics of two pathogenic P. wickerhamii strains and one environmental strain were analysed. Interestingly, mannan endo-1,4-β-mannosidase was significantly downregulated in P. wickerhamii S1, which contributes to a thinner cell wall in S1 compared to strains with typical colony morphology, and the toxicity of macrophages is reduced. Metabolite analysis revealed that the mucoid appearance of P. wickerhamii S1 may have been caused by an increase in linoleic acid, glycerol, and other metabolites. There is still a need to better understand the ecology, aetiology, and pathogenesis of P. wickerhamii, and in particular, its transmission between humans, animals, and the environment, from a One Health perspective.

Prototheca are unicellular, achlorophyllous, yeast-like microalgae that occur in a wide range of natural habitats. At least five species have been implicated as the causative agents of opportunistic infections of men. Human protothecosis typically manifests as cutaneous, articular, or systemic disease. Treatment is largely empirical with poorly predictable and often unsuccessful outcomes. This is largely due to the frequently observed resistance of Prototheca species to conventional antimicrobial agents. This work is the first to perform drug susceptibility profiling exclusively on isolates from human cases of protothecosis. A total of 23 such isolates were tested against amphotericin B and 9 azoles, including efinaconazole and luliconazole, whose activities against Prototheca have never been studied before. Efinaconazole was the most active, with median minimum inhibitory concentration (MIC) and minimum algicidal concentration (MAC) values of 0.031 mg/L and 0.063 mg/L, respectively. Fluconazole and luliconazole had the lowest activity, with median MIC and MAC values of 128 mg/L. To conclude, amphotericin B and most of the azoles showed in vitro activity, with an algicidal rather than algistatic effect, against Prototheca. Still, the activity of individual drugs differed significantly between the species and even between strains of the same species. These differences can be attributed to a species-specific potential for acquiring drug resistance, which, in turn, might be linked to the treatment history of the patient from whom the strain was recovered. The results of this study underscore the potential clinical utility of efinaconazole as a promising therapeutic agent for the treatment of human protothecosis.

We describe a case of extensive human cutaneous protothecosis in the northeastern of Brazil. The diagnosis was made through histopathological examination of skin samples and culturing on Sabouraud dextrose agar, with identification through mass spectrometry. Treatment with itraconazole failed and was switched to liposomal amphotericin followed by voriconazole with clinical cure. Prothotecosis should be a diagnostic hypothesis when there are skin lesions after trauma, specially in situations of atypical evolution.

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.

BACKGROUND: Protothecosis is a rare infection in humans and animals caused by the achlorophyllic algae Prototheca species. More than half of the protothecosis cases are cutaneous infections, and most cases are observed in immunocompromised individuals.
METHODS: We report a case of Prototheca wickerhamii infection in the mucosa of the pharynx in a 53-year-old immunocompetent woman with an incidentally found mass lesion at the left tongue base. Histopathological findings of the mass lesion suggested cryptococcosis, but P. wickerhamii was identified from the oropharynx scrape culture based on DNA sequencing. After surgical resection, fosfluconazole treatment was initiated, and subsequently, treatment was switched to topical amphotericin B. The residual mass lesion did not deteriorate during the 4-month antifungal treatment and 1-year observational period.
CONCLUSIONS: Prototheca species can be easily misdiagnosed as yeasts because of their morphological and pathological similarities. Prototheca, in addition to Cryptococcus should be considered if slow-growing, large Gram-positive organisms are encountered. Lactophenol cotton blue staining of the colony helps distinguish these organisms. Further study is needed to determine the appropriate treatment according to the infection focus.

We report the first published case of Prototheca wickerhamii breast implant infection. This occurred after mastectomy, chemotherapy, radiotherapy, breast reconstruction, implant revisions and breast seroma aspirations and was preceded by polymicrobial infection. Definitive treatment required implant removal and intravenous liposomal amphotericin B. The management of breast prosthesis infections is discussed.

Prototheca species have been reported to cause infections in human. Typically, clinical symptoms of protothecosis include cutaneous infection, olecranon bursitis, tenosynovitis and disseminated systemic disease. We report a case of septic arthritis in which Prototheca zopfii was isolated from blood. Joint aspirate was also sent for cultures but did not yield any growth. No other organisms were isolated from this patient during his admission. The blood isolate was identified to species level via Polymerase Chain Reaction (PCR) method. The patient improved with administration of intravenous itraconazole.

Prototheca spp. are achlorophyllous algae, ubiquitous in nature. An increasing number of human and animal cases of Prototheca infection (protothecosis) are reported, and antifungal azoles, which inhibit sterol 14α-demethylase (CYP51/ERG11) involved in ergosterol biosynthesis, have empirically been used for the treatment of protothecosis. Although Prototheca, like fungi, has ergosterol in the cell membrane, efficacy of the antifungal azoles in the treatment of protothecosis is controversial. For investigating the interaction of azole drugs with Prototheca CYP51/ERG11, the CYP51/ERG11 genomic genes of four strains of P. wickerhamii and one strain each of P. cutis and P. miyajii were isolated and characterized in this study. Compared with the CYP51/ERG11 gene of chlorophyllous Auxenochlorella Protothecoides, it is possible that ProtothecaCYP51/ERG11 gene, whose exon-intron structure appeared to be species-specific, lost introns associated with the loss of photosynthetic activity. Analysis of the deduced amino acid sequences revealed that Prototheca CYP51/ERG11 and fungal CYP51/ERG11 are phylogenetically distant from each other although their overall structures are similar. Our basic in silico studies predicted that antifungal azoles could bind to the catalytic pocket of Prototheca CYP51/ERG11. It was also suggested that amino acid residues away from the catalytic pocket might affect the drug susceptibility. The results of this study may provide useful insights into the phylogenetic taxonomy of Prototheca spp. in relationship to the CYP51/ERG11 structure and development of novel therapeutic drugs for the treatment of protothecosis.
UNASSIGNED: Cases of infection by microalgae of Prototheca species are increasing. However, effective treatment has not been established yet. In this study, gene and structure of Prototheca\'s CYP51/ERG11, an enzyme which might serve as a target for therapeutic drugs, were characterized for the first time.