Dataset Information

Transcriptomic Crosstalk between Fungal Invasive Pathogens and Their Host Cells: Opportunities and Challenges for Next-Generation Sequencing Methods.

ABSTRACT: Fungal invasive infections are an increasing health problem. The intrinsic complexity of pathogenic fungi and the unmet clinical need for new and more effective treatments requires a detailed knowledge of the infection process. During infection, fungal pathogens are able to trigger a specific transcriptional program in their host cells. The detailed knowledge of this transcriptional program will allow for a better understanding of the infection process and consequently will help in the future design of more efficient therapeutic strategies. Simultaneous transcriptomic studies of pathogen and host by high-throughput sequencing (dual RNA-seq) is an unbiased protocol to understand the intricate regulatory networks underlying the infectious process. This protocol is starting to be applied to the study of the interactions between fungal pathogens and their hosts. To date, our knowledge of the molecular basis of infection for fungal pathogens is still very limited, and the putative role of regulatory players such as non-coding RNAs or epigenetic factors remains elusive. The wider application of high-throughput transcriptomics in the near future will help to understand the fungal mechanisms for colonization and survival, as well as to characterize the molecular responses of the host cell against a fungal infection.

SUBMITTER: Enguita FJ

PROVIDER: S-EPMC5753088 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Transcriptomic Crosstalk between Fungal Invasive Pathogens and Their Host Cells: Opportunities and Challenges for Next-Generation Sequencing Methods.

Enguita Francisco J FJ Costa Marina C MC Fusco-Almeida Ana Marisa AM Mendes-Giannini Maria José MJ Leitão Ana Lúcia AL

Journal of fungi (Basel, Switzerland) 20160114 1

Fungal invasive infections are an increasing health problem. The intrinsic complexity of pathogenic fungi and the unmet clinical need for new and more effective treatments requires a detailed knowledge of the infection process. During infection, fungal pathogens are able to trigger a specific transcriptional program in their host cells. The detailed knowledge of this transcriptional program will allow for a better understanding of the infection process and consequently will help in the future de ...[more]

PMID: 29376924

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Project description:BackgroundTimely diagnosis and appropriate antifungal therapy are critical for improving the prognosis of patients with invasive fungal disease (IFD) after hematopoietic stem cell transplantation (HSCT). We evaluated the performance of metagenomic next-generation sequencing (mNGS) and conventional microbiological testing (CMT), as well as the diagnosis, therapeutic management, and outcomes of IFD after HSCT.MethodsWe retrospectively studied 189 patients who underwent HSCT and were considered at risk for IFD. In total, 46 patients with IFD were enrolled in this study. The IFD consensus was followed for classifying IFD incidents.ResultsForty-six patients were diagnosed with proven/probable (n = 12), possible (n = 27), and undefined (n = 7) IFD. Aspergillus was the most commonly detected fungal genus. Mucormycosis was found in 15 patients; two had Aspergillus, and one had Candida infections. Compared to CMT, mNGS significantly reduced the time required to identify pathogens (P = 0.0016). mNGS had a much higher sensitivity than CMT (84.78% vs. 36.96%; P < 0.0001). A total of 76.09% of patients received antifungal prophylaxis during fungal infections. All Pneumocystis infections occurred later than 100 days after transplantation. Among patients with Pneumocystis infection, 71.43% occurred following sulfonamide withdrawal, and subsequent treatment with sulfonamide alone or in combination with other drugs was effective. Based on the empirical antifungal treatment, the dosages, modes of administration, frequency of administration, or antifungal of 55.26% of the patients were changed according to the mNGS results. The 4-year overall survival rate of patients diagnosed with IFD after transplantation was 71.55% (95% CI, 55.18%-85.82%). Hypoproteinemia and corticosteroid use are independent risk factors for IFD.ConclusionmNGS, which has a high sensitivity and a short detection time, aids in the diagnosis and prognosis of pathogenic fungi. As a powerful technology, mNGS can influence treatment decisions in patients with IFD following HSCT.

Dataset Information

Transcriptomic Crosstalk between Fungal Invasive Pathogens and Their Host Cells: Opportunities and Challenges for Next-Generation Sequencing Methods.

Publications

Transcriptomic Crosstalk between Fungal Invasive Pathogens and Their Host Cells: Opportunities and Challenges for Next-Generation Sequencing Methods.

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