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ABSTRACT: Non-tuberculosis mycobacteria remodel infectious communities in cystic fibrosis associated respiratory infections.

PROVIDER: PRJNA1152493 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR30398300_1.fastq.gz	Fastqsanger.gz
	SRR30398300_2.fastq.gz	Fastqsanger.gz
	SRR30398301_1.fastq.gz	Fastqsanger.gz
	SRR30398301_2.fastq.gz	Fastqsanger.gz
	SRR30398302_1.fastq.gz	Fastqsanger.gz

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CIMENT

Project description:Epidemiology and Clinical Characteristics of Non-Tuberculous Mycobacteria Infections in Cystic Fibrosis Patients. (CIMENT)

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Expression data from Burkholderia multivorans ATCC 17616 wild-type and Bmul_2557 (ldhR) gene deletion mutant

Project description:Within this work we identified and characterized gene Bmul_2557 (ldhR) of B. multivorans ATCC 17616, a bacterial species associated with chronic respiratory infections in cystic fibrosis patients. LdhR belongs to the LysR-type family of transcriptional regulators and its deletion from the B. multivorans genome affected considerably the formation of planktonic cellular aggregates and surface-attached biofilms.

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Whole blood gene expression to predict susceptibility to nontuberculous mycobacterial pulmonary disease in adults with cystic fibrosis

Project description:Background: Patients with cystic fibrosis (CF) have an elevated lifetime risk of infection and disease caused by nontuberculous mycobacteria (NTM). Currently, there is no method to predict whether patients with cystic fibrosis will develop disease related to non-tuberculous mycobacteria. In non cystic fibrosis populations, several genetic susceptibility factors have been described. In this study, we examined whether patients with cystic fibrosis demonstrate a similar pattern of genetic susceptibility and explored host immune-related biomarkers predictive of NTM pulmonary disease (NTM-PD). Methods: We evaluated whole blood gene expression using bulk RNA-seq in a cohort of CF patients at the time of first isolation of NTM. Differential gene expression was compared in patients who did (n = 12) vs. did not (n= 30) develop NTM-PD following first NTM growth. Results: No differences in demographics or composition of white blood cell sample populations at the time of sample collection were identified between groups. There were no significant differences in the expression of genes previously reported to confer susceptibility to NTM-PD in non-CF populations. However, CF patients who went on to develop NTM-PD had higher expression of genes involved in the interferon ( and ), tumor necrosis factor, and IL6 STAT3 JAK pathways. Conclusion: Patients with CF who develop NTM-PD have increased expression of genes involved in innate immunity, in contrast to non-CF populations where these responses seem to be suppressed.

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Computational drug repositioning identifies niclosamide and tribromsalan as inhibitors of Mycobacterium tuberculosis and Mycobacterium abscessus

Project description:Tuberculosis (TB) is still a major global health challenge, killing over 1.5 million people each year, and hence, there is a need to identify and develop novel treatments for Mycobacterium tuberculosis (M. tuberculosis). The prevalence of infections caused by nontuberculous mycobacteria (NTM) is also increasing and has overtaken TB cases in the United States and much of the developed world. Mycobacterium abscessus (M. abscessus) is one of the most frequently encountered NTM and is difficult to treat. We describe the use of drug-disease association using a semantic knowledge graph approach combined with machine learning models that has enabled the identification of several molecules for testing anti-mycobacterial activity. We established that niclosamide (M. tuberculosis IC90 2.95 μM; M. abscessus IC90 59.1 μM) and tribromsalan (M. tuberculosis IC90 76.92 μM; M. abscessus IC90 147.4 μM) inhibit M. tuberculosis and M. abscessus in vitro. To investigate the mode of action, we determined the transcriptional response of M. tuberculosis and M. abscessus to both compounds in axenic log phase, demonstrating a broad effect on gene expression that differed from known M. tuberculosis inhibitors. Both compounds elicited transcriptional responses indicative of respiratory pathway stress and the dysregulation of fatty acid metabolism. Further testing against drug-resistant isolates and other NTM is warranted to clarify the usefulness of these repurposed drugs for mycobacteria.

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Project description:Nontuberculous mycobacteria disease in cystic fibrosis

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