Comprehensive circRNA-microRNA-mRNA network analysis revealed the novel regulatory mechanism of Trichosporon asahii infection.

BACKGROUND: Invasive Trichosporon asahii (T. asahii) infection frequently occurs with a high mortality in immunodeficient hosts, but the pathogenesis of T. asahii infection remains elusive. Circular RNAs (circRNAs) are a type of endogenous noncoding RNA that participate in various disease processes. However, the mechanism of circRNAs in T. asahii infection remains completely unknown. METHODS: RNA sequencing (RNA-seq) was performed to analyze the expression profiles of circRNAs, microRNAs (miRNAs), and mRNAs in THP-1 cells infected with T. asahii or uninfected samples. Some of the RNA-seq results were verified by RT-qPCR. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to analyze the differentially expressed mRNAs. A circRNA-miRNA-mRNA network was constructed and verified by dual-luciferase reporter assay and overexpression experiments. RESULTS: A total of 46 circRNAs, 412 mRNAs and 47 miRNAs were differentially expressed at 12 h after T. asahii infection. GO and KEGG analyses showed that the differentially expressed mRNAs were primarily linked to the leukocyte migration involved in the inflammatory response, the Toll-like receptor signaling pathway, and the TNF signaling pathway. A competing endogenous RNA (ceRNA) network was constructed with 5 differentially expressed circRNAs, 5 differentially expressed miRNAs and 42 differentially expressed mRNAs. Among them, hsa_circ_0065336 was found to indirectly regulate PTPN11 expression by sponging miR-505-3p. CONCLUSIONS: These data revealed a comprehensive circRNA-associated ceRNA network during T. asahii infection, thus providing new insights into the pathogenesis of the T. asahii-host interactions.

Prosthetic valve endocarditis by Trichosporon mucoides: A case report and review of literature.

NATIONALE: Trichosporon species are widely distributed in nature and are emerging opportunistic human pathogens. Trichosporon infections are associated with superficial cutaneous involvement in immunocompetent individuals to severe systemic disease in immunocompromised patients. Until now, there is no report in infective endocarditis by Trichosporon mucoides confirmed by molecular diagnostics PATIENT CONCERNS:: A 66-year-old man presented with a fever that had occurred for a period of 6 months. He had undergone aortic valve replacement 10 years prior. Transthoracic echocardiography showed vegetations on the prosthetic aortic valve and native mitral valve. T mucoides was detected in the cultures of blood and vegetations. DIAGNOSIS: DNA sequencing using D/D2 region of rRNA and internal transcribed spacer were performed. INTERVENTIONS: Infections were successfully controlled with valve replacement and voriconazole plus liposomal amphotericin B therapy. OUTCOMES: There has been no sign of recurrence for 18-months after treatment completion. LESSONS: This is the first reported case of infective endocarditis due to T mucoides. Clinicians should consider Trichosporon species as causative agents of endocarditis in patients who have undergone cardiac surgery.

Trichosporon-Blood Stream Infection.

AIM: Trichosporon species are the major emerging opportunistic pathogen in immunocompromised patients. Its diverse refractoriness to conventional antifungal drugs and association with high mortality rate is worrisome. The present study aims to determine the risk factors, treatment outcome and antifungal susceptibility pattern of Trichosporon species in blood stream infections. MATERIAL AND METHODS: All patients with blood culture positive for Trichosporon species from January 2012 to August 2016 at PD Hinduja National Hospital and research centre were evaluated retrospectively. Species identification and antifungal susceptibility by broth microdilution method for various drugs was determined using Vitek2 compact automated system. RESULTS: 12 patients were found to have Trichosporon blood stream infection. 9 isolates that were speciated all were T. asahii. All patients had central venous catheter and received prior antibiotics. Overall mortality rate was 50%. CONCLUSION: Higher mortality was associated with central venous catheter and voriconazole should be used as drug of choice for treatment. Identification of Trichosporon species along with its sensitivity and proper treatment of patients is of utmost importance.

Trichosporon asahii infection presenting as chronic meningo-ventriculitis and intra ventricular fungal ball: a case report and literature review.

Central nervous system trichosporonosis is a rare clinical entity and so far only six cases including three each of brain abscess and meningitis has been on record. We report a rare case of chronic meningo-ventriculitis and intraventricular fungal ball due to Trichosporon asahii in an 18-year-old immunocompetent male from Burundi, east Africa. Neuroendoscopy showed multiple nodules and a fungal ball within the ventricle, which on culture grew T. asahii. He was initially empirically treated with liposomal amphotericin B. However, the antifungal susceptibility testing of T. asahii isolate revealed high minimum inhibitory concentration for amphotericin B (2 µg ml⁻¹), flucytosine (16 µg ml⁻¹) and caspofungin (2 µg ml⁻¹) but exhibited potent activity for voriconazole, posaconazole, itraconazole and fluconazole. The patient rapidly succumbed to cardiac arrest before antifungal therapy could be changed. Although disseminated trichosporonosis has been increasingly reported the diagnosis represents a challenge especially in rare clinical settings such as intraventricular fungal ball in the present case, which has not been described previously.

Non-healing ulcer due to Trichosporon loubieri in an immunocompetent host and review of published reports.

We report here a case of non-healing ulcer due to Trichosporon loubieri in an apparently immunocompetent female. The identity of isolate was confirmed by DNA sequencing of D1/D2 region of 26S rDNA. The minimum inhibitory concentrations of the isolate were amphotericin B-0.5 µg/ml; fluconazole-4 µg/ml; posaconazole-0.25 µg/ml; voriconazole-0.06 µg/ml. The patient was managed by extensive debridement and oral fluconazole 150 mg daily for 6 weeks. She responded to therapy. To the best of our knowledge, till date, this is the fourth report of human infection due to T. loubieri and the first of its kind in an immunocompetent host. A review of published literature on infections due to T. loubieri is also included.

[An overview on Trichosporon asahii and its infections]. / Trichosporon asahii ve Enfeksiyonlarina Genel Bakis

Trichosporon species cause systemic, mucosa associated and superficial infections which include white piedra. Disseminated fungal infections due to Trichosporon species have increased in the recent years. Hematologic malignancy, cytotoxic chemotherapy, and organ transplantation are the main risk factors for disseminated Trichosporon infections. Two most common species that cause the disseminated Trichosporon infections are Trichosporon asahii and Trichosporon mucoides. Diagnosis and treatment of Trichosporon infections are difficult. Invasive trichosporonosis caused by T.asahii has a high mortality rate and a very poor prognosis. Fungicidal activity of amphotericin B against T.asahii isolates is inadequate. For echinocandin group of drugs, high minimum inhibitory concentration (MIC, µg/ml) values are obtained. Currently, triazole antifungal agents are the preferred drugs for the treatment of Trichosporon infections. In this review article general characteristics of T.asahii and its infections were summarized.