# Elucidation of a novel mechanism of macrolide resistance in Mycobacterium abscessus

> **NIH NIH R21** · WADSWORTH CENTER · 2020 · $204,155

## Abstract

Project Summary:
 Mycobacterium abscessus (Mab) is a rapidly growing NTM causing skin and soft tissue infections
and pulmonary infections in patients with chronic lung damage, such as prior tuberculosis and cystic
fibrosis. Mab stands apart as one of the most antibiotic resistant microbial species, making its infections
incredibly difficult to treat. Although macrolides are a cornerstone of therapy against NTMs, they are
ineffective against Mab. Intrinsic resistance to macrolides is attributed to macrolide inducible expression
of methylases that modify the 23S rRNA comprising the macrolide binding site. To date this is the only
known mechanism of macrolide resistance in Mab.
 We have identified an additional determinant, MAB_3042c, that confers inducible macrolide resistance
in Mab. MAB_3042c is homologous to the universally conserved HflX proteins which have been shown to
function as ribosome splitting factors. HflX proteins have not been previously implicated in antibiotic
resistance suggesting that Mab_3402 could be a novel type of HflX. However, Mab_3402 also shows
similarity to ribosome protection factors, which are characterized by an extended loop that inserts into the
nascent polypeptide exit tunnel (NPET) and occludes the binding pocket of macrolides.
 In this project we will explore the function of Mab_3042 in macrolide resistance in Mab. In Aim 1, we
will determine the function of MAB_3042c in ribosome splitting and ribosome protection as well as
determine the role of these functions in macrolide resistance. In Aim 2 we will study the spectrum of
antibiotics that are affected by MAB_3042c. The findings will provide a platform for a long-term structure-
function study to gain mechanistic insight into Mab_3402c dependent macrolide resistance in Mab.

## Key facts

- **NIH application ID:** 9936348
- **Project number:** 5R21AI146774-02
- **Recipient organization:** WADSWORTH CENTER
- **Principal Investigator:** Pallavi Ghosh
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $204,155
- **Award type:** 5
- **Project period:** 2019-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9936348

## Citation

> US National Institutes of Health, RePORTER application 9936348, Elucidation of a novel mechanism of macrolide resistance in Mycobacterium abscessus (5R21AI146774-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9936348. Licensed CC0.

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