# A novel mechanism of rifamycin resistance in Mycobacterium abscessus mediated by a putative helicase

> **NIH NIH R21** · WADSWORTH CENTER · 2022 · $189,135

## Abstract

Project Summary:
 Mycobacterium abscessus (Mab) is a rapidly growing NTM causing skin and soft tissue infections
as well as pulmonary infections in patients with chronic lung damage. Mab stands apart as one of the most
antibiotic resistant microbial species, making its infections incredibly difficult to treat. Particularly striking is
its resistance to rifampicin (RIF), a frontline drug for many mycobacterial infections including tuberculosis.
RIF inhibits global RNA synthesis by binding to the b-subunit of bacterial RNA polymerase; additionally it
is also known to inhibit replication initiation due to an inhibition of dnaA expression. The intrinsic RIF
resistance in Mab has so far been attributed to the presence of an ADP-ribosyltransferase (Arr) activity
that ribosylates RIF leading to its inactivation. However, we have recently identified an additional
determinant, MAB_3189c - a putative helicase, that confers high levels of RIF resistance in Mab.
MAB_3189c expression is RIF inducible and is likely regulated by a RIF-associated element (RAE)
dependent transcription factor. In this project we will determine the regulation and function of Mab3189c
in RIF resistance. In Aim 1 we will investigate if Mab3189c mediates RIF resistance by either directly
protecting RNAP against the action of RIF thereby enabling global RNA synthesis to continue, or by
alleviating RIF-sensitive replication initiation at oriM thereby enabling growth in the presence of RIF. In Aim
2 we propose to identify the regulatory protein required for RAE-dependent induction of MAB_3189c. The
findings will provide a platform for a long-term study to gain insights into Mab3189c dependent RIF
resistance in Mab, and design of new strategies to treat Mab infections.

## Key facts

- **NIH application ID:** 10408177
- **Project number:** 5R21AI159125-02
- **Recipient organization:** WADSWORTH CENTER
- **Principal Investigator:** Pallavi Ghosh
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $189,135
- **Award type:** 5
- **Project period:** 2021-05-20 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10408177

## Citation

> US National Institutes of Health, RePORTER application 10408177, A novel mechanism of rifamycin resistance in Mycobacterium abscessus mediated by a putative helicase (5R21AI159125-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10408177. Licensed CC0.

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