Chromosomal beta-lactam resistance in enterobacteria

Area of Science:

• Microbiology
• Molecular Biology
• Genetics

Background:

• Most enterobacteria possess a chromosomal ampC beta-lactamase gene.
• In Escherichia coli and Shigella, ampC expression is non-inducible, resulting in low beta-lactamase levels.
• Resistance to modern cephalosporins is rare in these species due to infrequent mutations.

Purpose of the Study:

• To investigate the regulation of ampC beta-lactamase expression in enterobacteria.
• To understand the genetic basis of cephalosporin resistance in species with inducible ampC.
• To identify key genes involved in ampC regulation and their impact on resistance.

Main Methods:

• Analysis of ampC gene expression in various enterobacterial species.
• Genetic studies involving mutations in ampR and ampD regulatory genes.
• Assessment of beta-lactamase inducibility and production levels.

Main Results:

• In Enterobacter cloacae and Citrobacter freundii, ampC expression is induced by beta-lactams and regulated by ampR and ampD.
• Mutations in ampR eliminate beta-lactamase inducibility, leading to low constitutive levels.
• Mutations in ampD, with an intact ampR, cause high-frequency, constitutive overproduction of ampC beta-lactamase.

Conclusions:

• AmpD mutations are a frequent cause of clinical resistance to third-generation cephalosporins in enterobacteria with inducible ampC.
• The ampR and ampD genes play critical roles in the regulation of ampC beta-lactamase.
• Understanding these regulatory mechanisms is crucial for combating antibiotic resistance.