# Interactions between translation inhibiting antibiotics and diverse RNA regulatory mechanism in pathogenic bacteria affect drug sensitivity

> **NIH NIH R21** · BOSTON COLLEGE · 2021 · $234,750

## Abstract

Interactions between translation inhibiting antibiotics and diverse RNA regulatory
 mechanisms affect drug sensitivity in pathogenic bacteria
Summary: RNA regulatory mechanisms leverage the tight linkage between transcription, translation, and RNA
secondary structure to regulate gene expression through a variety of mechanisms including intrinsic transcription
termination, RNA degradation, and translation efficiency. Furthermore, despite findings that a variety of RNA
regulators have significant impacts on pathogenicity and virulence, the prevalence of these mechanisms across
diverse bacteria is very different. In reaction to sub-inhibitory antibiotics, including translation inhibiting antibiotics
(TIAs), different pathogens display diverse physiological responses, driven by wide-spread gene expression
changes, that ultimately contribute to the emergence and maintenance of antibiotic resistance. How antibiotics,
especially TIAs, affect different types of RNA regulatory mechanisms and thereby contribute to such responses
and drug sensitivity is largely unknown. The objective of this proposal is to assess how subinhibitory TIAs interact
with RNA regulators to impact transcript boundaries and RNA folding in two bacterial pathogens (Streptococcus
pneumoniae and Acinetobacter baumannii) that display diverse paradigms of RNA regulation. We hypothesize
that interactions between subinhibitory TIAs and distinct types of RNA regulatory mechanisms have a
significant impact on the pathogen’s physiological response and thus drug sensitivity. The rationale for
the proposed research is to generate a generalizable mechanistic connection between the subinhibitory doses
of TIAs and their physiological effects. To achieve this objective there are two specific aims: 1) Identify changes
to transcript boundaries induced by translation inhibiting antibiotics; and 2) establish mRNA structure changes
induced by translation inhibiting antibiotics. These aims will be achieved through the use of innovative new
sequencing technologies that reach beyond standard coding-transcriptome analysis to evaluate the impact of
translation inhibiting antibiotics on transcript boundaries and RNA secondary structure and accessibility. This
proposal addresses a significant question whose answer will not only provide insight into the specific organisms
examined here, but will also change how past and future transcriptomic studies in bacterial pathogens are
analyzed. The expected outcome of this study is a connection between types of RNA regulatory mechanisms
within two important pathogens and the physiological effects of subinhibitory TIAs. Furthermore, this knowledge
may link genomic features, such as the presence of the termination protein Rho or RNA chaperone Hfq, with
observed responses to subinhibitory TIAs that play a role in drug sensitivity and resistance emergence.

## Key facts

- **NIH application ID:** 10133517
- **Project number:** 5R21AI148895-02
- **Recipient organization:** BOSTON COLLEGE
- **Principal Investigator:** Michelle Margaret Meyer
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $234,750
- **Award type:** 5
- **Project period:** 2020-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10133517

## Citation

> US National Institutes of Health, RePORTER application 10133517, Interactions between translation inhibiting antibiotics and diverse RNA regulatory mechanism in pathogenic bacteria affect drug sensitivity (5R21AI148895-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10133517. Licensed CC0.

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