Oct 14, 2017

Envelope proteome changes driven by RamA overproduction in Klebsiella pneumoniae that enhance acquired β-lactam resistance

The Journal of Antimicrobial Chemotherapy
Juan-Carlos Jiménez-CastellanosMatthew B Avison

Abstract

In Klebsiella pneumoniae, overproduction of RamA results in reduced envelope permeability and reduced antimicrobial susceptibility but clinically relevant resistance is rarely observed. Here we have tested whether RamA overproduction can enhance acquired β-lactam resistance mechanisms in K. pneumoniae and have defined the envelope protein abundance changes upon RamA overproduction during growth in low and high osmolarity media. Envelope permeability was estimated using a fluorescent dye accumulation assay. β-Lactam susceptibility was measured using disc testing. Total envelope protein production was quantified using LC-MS/MS proteomics and transcript levels were quantified using real-time RT-PCR. RamA overproduction enhanced β-lactamase-mediated β-lactam resistance, in some cases dramatically, without altering β-lactamase production. It increased production of efflux pumps and decreased OmpK35 porin production, though micF overexpression showed that OmpK35 reduction has little impact on envelope permeability. A survey of K. pneumoniae bloodstream isolates revealed ramA hyperexpression in 3 of 4 carbapenemase producers, 1 of 21 CTX-M producers and 2 of 19 strains not carrying CTX-M or carbapenemases. Whilst RamA is not a key med...Continue Reading

Mentioned in this Paper

Real-Time Polymerase Chain Reaction
Fluorescent Dyes
Laboratory Procedures
Gene Products, env
Carbapenemase
Bacterial Proteins
Osmolarity Measurement
Klebsiella pneumoniae
Protein Function
Multidrug Efflux Pump Activity

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