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Molecular analysis of the translational attenuator of a constitutively expressed erm(A) gene from Staphylococcus
1Institut für Tierzucht und Tierverhalten der Bundesforschungsanstalt für Landwirtschaft (FAL), Dörnbergstrabetae 25-27, 29223 Celle, Germany.
Abstract:
During the course of a study on macrolide, lincosamide and streptogramin B resistance among staphylococci from animal sources, a Staphylococcus intermedius isolate was found to carry a constitutively expressed erm(A) gene on the 70 kb plasmid pSES29. The molecular basis of constitutive erm(A) expression was investigated by cloning and sequence analysis of the erm(A)-associated translational attenuator. Two point mutations in this regulatory region were detected. These mutations cause constitutive erm(A) gene expression by destabilization of mRNA secondary structures required for the inducible type of erm(A) gene expression.
Insights
Constitutive erm(A) gene expression in Staphylococcus intermedius was linked to two mutations. These genetic changes destabilize mRNA, bypassing normal inducible resistance mechanisms for macrolide, lincosamide, and streptogramin B antibiotics.
Area of Science:
- Microbiology
- Molecular Biology
- Antimicrobial Resistance
Background:
- Staphylococci from animal sources are reservoirs for antibiotic resistance genes.
- The erm(A) gene confers resistance to macrolide, lincosamide, and streptogramin B antibiotics.
- Inducible expression of erm(A) is typically regulated by a translational attenuator.
Purpose of the Study:
- To investigate the molecular basis of constitutive erm(A) gene expression in a Staphylococcus intermedius isolate.
- To identify genetic alterations in the erm(A)-associated translational attenuator responsible for constitutive expression.
Main Methods:
- Cloning of the erm(A) gene and its regulatory region.
- DNA sequencing of the erm(A)-associated translational attenuator.
- Analysis of mRNA secondary structures involved in gene regulation.
Main Results:
- A Staphylococcus intermedius isolate exhibited constitutive erm(A) expression.
- Two point mutations were identified within the translational attenuator region of the erm(A) gene.
- These mutations were shown to destabilize the mRNA secondary structures essential for inducible erm(A) expression.
Conclusions:
- The identified mutations in the translational attenuator directly cause constitutive erm(A) gene expression.
- This constitutive expression mechanism bypasses the typical inducible resistance pathway.
- Understanding these mechanisms is crucial for monitoring and managing antibiotic resistance in staphylococci.