1887

Abstract

Several genetic regulators belonging to AraC family are involved in the emergence of MDR isolates of due to alterations in membrane permeability. Compared with the genetic regulator Mar, RamA may be more relevant towards the emergence of antibiotic resistance.

Focusing on the global regulators, Mar and Ram, we compared the amino acid sequences of the Ram repressor in 59 clinical isolates and laboratory strains of Sequence types were associated with their corresponding multi-drug resistance phenotypes and membrane protein expression profiles using MIC and immunoblot assays. Quantitative gene expression analysis of the different regulators and their targets (porins and efflux pump components) were performed.

In the majority of the MDR isolates tested, and a region upstream of were mutated but or were unchanged. Expression and cloning experiments highlighted the involvement of the locus in the modification of membrane permeability. Overexpression of RamA lead to decreased porin production and increased expression of efflux pump components, whereas overexpression of RamR had the opposite effects.

Mutations or deletions in leading to the overexpression of RamA predominated in clinical MDR isolates and were associated with a higher-level of expression of efflux pump components. It was hypothesised that mutations in and the self-regulating region proximal to probably altered the binding properties of the RamR repressor; thereby producing the MDR phenotype. Consequently, mutability of RamR may play a key role in predisposing towards the emergence of a MDR phenotype.

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2018-02-01
2020-09-23
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