# Discovering novel antimicrobial agents that target sRNA regulated antibiotic resistance mechanisms

> **NIH NIH SC2** · CALIFORNIA STATE UNIVERSITY NORTHRIDGE · 2020 · $145,000

## Abstract

PROJECT SUMMARY
The rise of antibiotic resistant pathogenic bacteria represents a major threat to human health that demands the
development of new strategies to combat resistance mechanisms. A significant challenge is overcoming
bacteria’s ability to limit the efficacy of antibiotics by reducing their intracellular concentration by increasing efflux
out of the cell and decreasing entry through membrane proteins. One method bacteria use to induce these
intrinsic resistance processes is through post-transcriptional regulation of genes by small RNAs (sRNAs). For
example, the sRNA MicF represses the translation of outer membrane protein F (OmpF), a porin involved in
antibiotic uptake. Transcription of MicF is known to increase due to environmental factors such as oxidative
stress and the presence of antibiotics. Here we propose an innovative antimicrobial treatment strategy whereby
we introduce a biomolecule designed to sequester MicF, thus increasing the efficacy of existing antibiotics by
increasing antibiotic uptake through the porin OmpF. To achieve this goal, we will first characterize changes in
the transcription of MicF during Escherichia coli’s response to representatives from the major classes of
antibiotics (Aim 1). Next, we will pursue two parallel strategies to design biomolecules that will bind and sequester
MicF in the cell. The first will be to design antisense molecules that bind directly to MicF (Aim 2). In the second
strategy, we will randomize amino acids of known RNA binding peptides to change their specificity to bind to
MicF (Aim 3). Initial validation will be done in E. coli; however, MicF is highly conserved in g-proteobacteria and
thus results from this work can be extended to other important pathogens. We expect our designed biomolecules
to increase susceptibility to a subset of antibiotics, thus reducing the impact of pathogenic bacteria on human
health. Furthermore, the strategy outlined here is generalizable and can be extended to other RNA regulation
mechanisms involved in antibiotic resistance.

## Key facts

- **NIH application ID:** 9933185
- **Project number:** 1SC2GM136500-01
- **Recipient organization:** CALIFORNIA STATE UNIVERSITY NORTHRIDGE
- **Principal Investigator:** Melissa K. Takahashi
- **Activity code:** SC2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $145,000
- **Award type:** 1
- **Project period:** 2020-03-23 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9933185

## Citation

> US National Institutes of Health, RePORTER application 9933185, Discovering novel antimicrobial agents that target sRNA regulated antibiotic resistance mechanisms (1SC2GM136500-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9933185. Licensed CC0.

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