16-membered ring macrolides and erythromycin induce ermB expression by different mechanisms
Weizhi He1, Kai Jiang2, Hua Qiu3
1Fudan University Shanghai Cancer Center, Institutes of Biomedical Sciences, Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Shanghai Medical College of Fudan University, Shanghai, 200032, China. hew12@fudan.edu.cn.
BMC Microbiology
|June 10, 2022
Summary
The translation of ermBL, a key protein, is crucial for inducing ermB gene expression by erythromycin and related macrolides. Different regions of ermBL are involved in this induction process.
Area of Science:
- Molecular Biology
- Microbiology
- Genetics
Background:
- Erythromycin (Ery) induces ermB expression via ribosome stalling on ermBL and mRNA stabilization.
- 16-membered ring macrolides also induce ermB expression, but the mechanism remains unclear.
Purpose of the Study:
- To investigate the mechanisms by which 16-membered ring macrolides induce ermB expression.
- To elucidate the roles of ermBL and ermBL2 in macrolide-induced ermB expression.
Main Methods:
- Introduction of premature termination codons, alanine-scanning mutagenesis, and amino acid mutations in ermBL and ermBL2.
- Analysis of ermB and ermC expression in response to different macrolides.
Main Results:
- 16-membered ring macrolides induce ermB but not ermC expression.
- Truncated ermB mutants revealed distinct regulatory regions for Ery and 16-membered ring macrolide induction.
- Translation of the ermBL N-terminal region is essential for induction by Ery, spiramycin (Spi), and tylosin (Tyl).
- ermBL2 is critical for Ery-induced ermB expression but not for induction by 16-membered ring macrolides.
Conclusions:
- Translation of ermBL and its C-terminal RNA sequence are critical for ermB expression induction by Spi and Tyl.
- Distinct molecular mechanisms underlie ermB induction by erythromycin and 16-membered ring macrolides.
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