# Identification of Mycobacterium tuberculosis genes that mediate inhibition of the host cell IFN-beta signaling

> **NIH NIH R21** · UNIV OF MARYLAND, COLLEGE PARK · 2021 · $191,171

## Abstract

Abstract
It is estimated that about one third of the world’s population is latently infected with Mycobacterium tuberculosis
(Mtb). The 10 million annual new cases of tuberculosis resulting in about one million deaths further underline the
global public health impact of this pathogen. Mtb has developed a multitude of pathways to evade the host
immune response. For the most part, the molecular mechanisms of these host pathogen interactions are only
beginning to be understood. The premise of the current proposal is supported by a series of novel and
unpublished results which demonstrate that Mtb inhibits IFN-a/b-receptor (IFNAR)-mediated cell signaling which
results in improved intracellular growth of the bacteria. These findings thus describe a novel immunoevasion
pathway engaged by Mtb. The central hypothesis of this application is that genetic screens will be able to identify
the genes in Mtb important for inhibition of the IFNAR-mediated cell signaling. In Aim 1.1 we propose to execute
a “gain-of-function” genetic screen using M. smegmatis clones transfected with a Mtb-DNA cosmid library. This
approach has been successfully executed for two other screens by the PI’s lab. Next, in Aim 1.2 we describe
how the relevant Mtb gene out of the approximately 40 genes in one of the isolated cosmids will be identified.
Overall, we anticipate that the successful completion of the current project will generate at least one Mtb deletion
mutant deficient in inhibition of IFNAR-mediated cell signaling and potentially the knowledge of several other Mtb
regions that contain additional genes. These findings will be the basis for a competitive R01 application which
will propose to: 1) complete the identification of all of the Mtb genes involved in inhibition of IFN-β-mediated cell
signaling, 2) to use the mutants for detailed analysis of the molecular mechanisms of the inhibition and 3) to
characterize the importance of inhibiting IFNAR-mediated cell signaling for in vivo virulence of Mtb.

## Key facts

- **NIH application ID:** 10076780
- **Project number:** 5R21AI142396-02
- **Recipient organization:** UNIV OF MARYLAND, COLLEGE PARK
- **Principal Investigator:** VOLKER BRIKEN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $191,171
- **Award type:** 5
- **Project period:** 2020-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10076780

## Citation

> US National Institutes of Health, RePORTER application 10076780, Identification of Mycobacterium tuberculosis genes that mediate inhibition of the host cell IFN-beta signaling (5R21AI142396-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10076780. Licensed CC0.

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