Mutant ribosomes can generate dominant kirromycin resistance

Area of Science:

• Microbiology
• Molecular Biology
• Genetics

Background:

• Kirromycin antibiotic targets elongation factor Tu (EF-Tu) in bacteria.
• Mutations in tufA and tufB genes confer recessive kirromycin resistance.
• Ribosomal protein S12 (RpsL) mutations can affect antibiotic resistance phenotypes.

Purpose of the Study:

• To investigate novel kirromycin resistance phenotypes in Salmonella typhimurium and Escherichia coli.
• To elucidate the role of interactions between mutant EF-Tu and mutant ribosomes in conferring antibiotic resistance.
• To determine the influence of streptomycin resistance mutations on kirromycin resistance.

Main Methods:

• Genetic analysis of Salmonella typhimurium and Escherichia coli strains.
• Phenotypic characterization of kirromycin and streptomycin resistance.
• Assessment of EF-Tu and ribosome interactions.

Main Results:

• A dominant kirromycin resistance phenotype was observed in strains with a single mutant tuf gene and an error-restrictive rpsL mutation.
• This dominant resistance is dependent on error-restrictive mutations and not observed with nonrestrictive ones.
• Mutant ribosomes exhibit altered interactions with EF-Tu, leading to increased kirromycin resistance and faster EF-Tu cycling.

Conclusions:

• Novel dominant kirromycin resistance mechanisms involve specific interactions between mutant EF-Tu and mutant ribosomes.
• Error-restrictive mutations play a crucial role in modulating EF-Tu-ribosome interactions and antibiotic resistance.
• These findings offer new insights into bacterial antibiotic resistance and EF-Tu function.