Abstract
Nosocomial isolates of Klebsiella pneumoniae resistant to all commonly used antimicrobial agents have emerged in many regions of the world. It is unknown if efflux systems contribute to the multidrug resistance phenotype. The expression of genes encoding the efflux pump AcrAB and the global regulators MarA, SoxS and RamA were examined and correlated with antimicrobial resistance. Twenty isolates belonged to the two important clones representing KPC-possessing strains endemic to our region. Virtually all of these isolates had negligible or absent expression of the genes, and resistance to fluoroquinolones and aminoglycosides could be explained by alternative mechanisms. All of these isolates were susceptible to tigecycline. A group of 14 heterogeneous isolates was also examined. There was a correlation between expression of marA with expression of soxS. Only expression of soxS was significantly correlated with expression of acrB. With a background substitution in GyrA, increased expression of acrB and marA appeared to contribute to fluoroquinolone resistance in some isolates. A correlation was noted between expression of soxS and ramA (but not marA and acrB) and tigecycline MICs. Following in vitro exposure to tigecycline, resistance occurred in association with a marked increase in marA and acrB expression in isolates lacking expression of soxS and ramA. While laboratory-derived tigecycline resistance was associated with increased acrB expression, the variation in tigecycline MICs in clinical isolates was associated only with selected regulator genes. It appears that other mechanisms beyond activation of the acrAB system mediate tigecycline resistance.
Highlights
Klebsiella pneumoniae resistant to all commonly used antimicrobial agents has emerged as a serious nosocomial pathogen in the north-eastern USA.[1]
We examine the expression and contribution of the acrAB efflux system and the three regulatory genes markedly increased expression of another (marA), soxS and ramA in: (i) two important clones that include multidrug-resistant K. pneumoniae; and (ii) a heterogeneous collection of clinical isolates of K. pneumoniae
Eleven isolates belonged to clonal group A, a strain that accounted for 88% of KPC-possessing K. pneumoniae in New York City.[18]
Summary
Klebsiella pneumoniae resistant to all commonly used antimicrobial agents has emerged as a serious nosocomial pathogen in the north-eastern USA.[1] The acquisition of the carbapenemase KPC has contributed to resistance to all b-lactams. These strains are frequently resistant to aminoglycosides and fluoroquinolones, and occasional isolates are resistant to the polymyxins and tigecycline.[1] It is unknown if antibiotic efflux plays a role in the multidrug resistance phenotype. The AcrAB efflux system, present in most Enterobacteriaceae, belongs to the resistance-nodulation-division (RND) family of transporters and utilizes the outer membrane protein TolC. Substrates for this efflux system have included fluoroquinolones, macrolides, chloramphenicol, trimethoprim and tetracycline.[2,3]
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