# INDUCIBLE ERYTHROMYCIN RESISTANCE

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 1990 · $163,326

## Abstract

The research proposed is in the general area of gene regulation studied in
a model system in which erythromycin specifically and efficiently induces
resistance to itself and other macrolides, to the lincosamides, and to the
streptogramin B (MLS) antibiotics.  Synthesis of the inducible 23S
ribosomal RNA methylase responsible for MLS resistance is controlled at the
translational level by an attenuator whose conformation regulates
expression by determining availability of the ribosome loading site for
translation initiation of the resistance methylase.  One of the main
unanswered questions in this work is:  What mechanism accounts for the
apparent wide variability of induction efficiency of different subsets of
MLS antibiotics in different bacteria despite the apparently equal
efficiency of these antibiotics as inhibitors?  The long term objective of
this proposal is to study and test models of regulation of gene expression
with emphasis on genes that specify antibiotic resistance; The specific
aims of this proposal are to study regulation of inducible MLS resistance
model systems by: (2) determining induction specificity in vivo following
insertion of chemically synthesized model leader sequences into expression
vectors constructed for this work, (2) determining amino acid sequence or
codon usage alterations in mutants that involve the leader peptide and show
possible associated altered specificity of induction, and (3) studying
induction specificity and attenuator function in new bacterial strains.
These studies of induction provide a model for understanding rapid
development of constitutive MLS resistance following a short course of
treatment with MLS antibiotics in a clinical setting.  Inducible MLS
resistance is also found in Streptomyces that produce MLS antibiotics and
in some instances resistance is not expressed before the cells enter
antibiotic production.  It is our working hypothesis that in nature, leader
peptides serve to optimize the coupling between antibiotic production and
development of resistance, or more generally, between inductive stimulus
and increased expression of specific genes.  Methods that will be used in
these studies include recombinant DNA technology and DNA sequencing applied
to cloning model DNA attenuator sequences synthesized by chemical means and
analyzing new control sequences from natural resources.

## Key facts

- **NIH application ID:** 3127807
- **Project number:** 5R01AI018283-10
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **SAM.gov UEI:** LCLSJAGTNZQ7
- **Principal Investigator:** Bernard Weisblum
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $163,326
- **Award type:** 5
- **Project period:** 1981-08-01 → 1991-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3127807

## Citation

> US National Institutes of Health, RePORTER application 3127807, INDUCIBLE ERYTHROMYCIN RESISTANCE (5R01AI018283-10). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3127807. Licensed CC0.

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