Induction of erm(C) expression by noninducing antibiotics
Marne Bailey1, Tobin Chettiath, Alexander S Mankin
1Center for Pharmaceutical Biotechnology--870, University of Illinois, 900 S. Ashland Ave., Chicago, IL 60607, USA.
Antimicrobial Agents and Chemotherapy
|December 19, 2007
Summary
Ketolides, a new class of antibiotics, can induce erm genes, contrary to prior beliefs. This induction, though weaker and slower than with macrolides, impacts bacterial resistance mechanisms.
Area of Science:
- Microbiology
- Molecular Biology
- Antibiotic Resistance
Background:
- Ketolides are the newest class of macrolide antibiotics.
- They are generally considered non-inducers of inducible erm genes.
- Understanding their effect on gene expression is crucial for antibiotic resistance research.
Purpose of the Study:
- To investigate the effects of ketolides and macrolides on the inducible erm(C) gene expression in Escherichia coli.
- To compare the induction kinetics and levels between ketolides and macrolides.
- To elucidate the mechanism of ketolide-induced erm gene expression.
Main Methods:
- Exposure of Escherichia coli to various macrolide and ketolide compounds.
- Measurement of 23S rRNA dimethylation at residue A2058.
- Utilizing a reporter construct for colorimetric detection of erm(C) induction in a disc diffusion assay.
- Analyzing the effect of erm(C) leader peptide deletion on induction.
Main Results:
- Both macrolides and ketolides increased A2058 dimethylation in 23S rRNA.
- Ketolides induced erm(C) expression, but with slower kinetics and lower levels compared to macrolides.
- Clinically relevant ketolides like telithromycin induced reporter expression within a narrower concentration range.
- Deletion of erm(C) leader peptide codons abolished macrolide induction but not ketolide induction.
Conclusions:
- Ketolides are generally capable of inducing erm genes.
- The induction by ketolides may be masked in standard Minimum Inhibitory Concentration (MIC) assays due to narrow concentration ranges and slower kinetics.
- This finding has implications for understanding and combating antibiotic resistance.
Related Concept Videos
01:23Stringent Response in E. coli
Bacterial growth is closely tied to nutrient availability, with cells proliferating exponentially under favorable conditions and entering a stationary phase when resources become scarce. This transition is mediated by a regulatory mechanism known as the stringent response, which allows bacteria to adapt to nutrient deprivation by modulating gene expression and metabolic activity.During nutrient scarcity, intracellular amino acid levels decline. It results in the accumulation of uncharged tRNAs...
01:25Inducible Operons: lac Operon
The lac operon in Escherichia coli is a model for understanding inducible gene regulation and metabolic flexibility. It integrates local control by lactose and global regulation through catabolite repression, enabling E. coli to preferentially metabolize glucose when available and switch to lactose utilization when glucose is scarce.Structure and Function of the lac OperonThe lac operon contains three structural genes: lacZ (β-galactosidase), lacY (lactose permease), and lacA (thiogalactoside...
00:57Antibiotic Selection
Overview
01:30Development of Antibiotic Resistance
Antibiotic resistance is a major public health concern that arises when bacteria evolve mechanisms to withstand the effects of antibiotic treatments. This resistance can be intrinsic, acquired through genetic mutations, or transferred between bacteria via horizontal gene transfer. The development of antibiotic resistance poses significant challenges in treating bacterial infections and necessitates ongoing research to develop new therapeutic strategies.Intrinsic resistance occurs when bacterial...
01:29Coordination of Gene Expression Processes in Bacteria
The DNA replication, transcription, and translation processes are intricately coupled in bacteria, allowing efficient gene expression and rapid protein synthesis. While this physical and functional coordination is advantageous, it introduces challenges that bacteria overcome through specific regulatory mechanisms.Coupling of Replication, Transcription, and TranslationThe coupling of replication, transcription, and translation is a hallmark of bacterial gene expression. As the replisome unwinds...
01:27Production of Antibiotics
Penicillin, one of the earliest and most widely used antibiotics, is produced industrially by the filamentous fungus Penicillium chrysogenum. Large stirred-tank bioreactors ranging from tens to hundreds of thousands of liters maintain tightly controlled temperature, pH, and dissolved oxygen conditions to support fungal metabolism and maximize antibiotic yield. Penicillin is a secondary metabolite, synthesized primarily during the stationary growth phase, which requires a carefully managed...