Abstract

Acinetobacter baumannii is opportunistic in debilitated hospitalised patients. Because information from some South American countries was previously lacking, this study examined the emergence of multi-resistant A. baumannii in three hospitals in Cochabamba, Bolivia, from 2008 to 2009. Multiplex PCR was used to identify the main resistance genes in 15 multi-resistant A. baumannii isolates. RT-PCR was used to measure gene expression. The genetic environment of these genes was also analysed by PCR amplification and sequencing. Minimum inhibitory concentrations were determined for key antibiotics and some were determined in the presence of an efflux pump inhibitor, 1-(1-napthylmethyl) piperazine. Fourteen strains were found to be multi-resistant. Each strain was found to have the blaOXA-58 gene with the ISAba3-like element upstream, responsible for over-expression of the latter and subsequent carbapenem resistance. Similarly, ISAba1, upstream of the blaADC gene caused over-expression of the latter and cephalosporin resistance; mutations in the gyrA(Ser83 to Leu) and parC (Ser-80 to Phe) genes were commensurate with fluoroquinolone resistance. In addition, the adeA, adeB efflux genes were over-expressed. All 15 isolates were positive for at least two aminoglycoside resistance genes. This is one of the first reports analyzing the multi-drug resistance profile of A. baumannii strains isolated in Bolivia and shows that the over-expression of theblaOXA-58, blaADC and efflux genes together with aminoglycoside modifying enzymes and mutations in DNA topoisomerases are responsible for the multi-resistance of the bacteria and the subsequent difficulty in treating infections caused by them.

Highlights

  • Acinetobacter baumannii is opportunistic in debilitated hospitalised patients

  • Gene caused over-expression of the latter and cephalosporin resistance; mutations in the gyrA(Ser83 to Leu) and parC (Ser-80 to Phe) genes were commensurate with fluoroquinolone resistance

  • All 15 isolates were positive for at least two aminoglycoside resistance genes. This is one of the first reports analyzing the multi-drug resistance profile of A. baumannii strains isolated in Bolivia and shows that the over-expression of theblaOXA-58, blaADC and efflux genes together with aminoglycoside modifying enzymes and mutations in DNA

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Summary

Introduction

Acinetobacter baumannii is opportunistic in debilitated hospitalised patients. Because information from some South American countries was previously lacking, this study examined the emergence of multi-resistant A. baumannii in three hospitals in Cochabamba, Bolivia, from 2008 to 2009. Acinetobacter baumannii is a pathogenic bacterium responsible for a wide range of infections such as septicaemia, meningitis, pneumonia and urinary tract infections and is one of the most important Gram-negative pathogens causing infections in immuno-compromised patients [1]. Acinetobacter baumannii has been considered the paradigm of multiresistant bacteria because of emerging multi-drug resistance to various antimicrobial agents [2], notably mutations in gyrA and parC genes that confer fluoroquinolone resistance and activation of the aminoglycoside inactivating enzymes [2,3,4]. Transposable elements play a major role in gene expression. They are generally tightly regulated and exercise their role in a strategic manner [5]. Insertion sequences carrying promoters are often responsible for driving the expression of the downstream antibiotic resistance gene, often leading to the over-expression of the gene, and making the bacterium resistant to various antibiotics [6]

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