Role of Novel Multidrug Efflux Pump Involved in Drug Resistance in Klebsiella pneumoniae

Abstract

BackgroundMultidrug resistant Klebsiella pneumoniae have caused major therapeutic problems worldwide due to the emergence of the extended-spectrum β-lactamase producing strains. Although there are >10 major facilitator super family (MFS) efflux pumps annotated in the genome sequence of the K. pneumoniae bacillus, apparently less is known about their physiological relevance.Principal FindingsInsertional inactivation of kpnGH resulting in increased susceptibility to antibiotics such as azithromycin, ceftazidime, ciprofloxacin, ertapenem, erythromycin, gentamicin, imipenem, ticarcillin, norfloxacin, polymyxin-B, piperacillin, spectinomycin, tobramycin and streptomycin, including dyes and detergents such as ethidium bromide, acriflavine, deoxycholate, sodium dodecyl sulphate, and disinfectants benzalkonium chloride, chlorhexidine and triclosan signifies the wide substrate specificity of the transporter in K. pneumoniae. Growth inactivation and direct fluorimetric efflux assays provide evidence that kpnGH mediates antimicrobial resistance by active extrusion in K. pneumoniae. The kpnGH isogenic mutant displayed decreased tolerance to cell envelope stressors emphasizing its added role in K. pneumoniae physiology.Conclusions and SignificanceThe MFS efflux pump KpnGH involves in crucial physiological functions besides being an intrinsic resistance determinant in K. pneumoniae.

Occurrence of Diverse Antimicrobial Resistance Determinants in Genetically Unrelated Biocide Tolerant Klebsiella pneumoniae

“…coli strain KAM32 resulted in elevated minimum inhibitory concentrations of chloramphenicol, norfloxacin, acriflavine, and ethidium bromide [19]. The efflux pumps kpnEF and kpnGH has been reported to display a role in conferring broad spectrum antimicrobial resistance previously [20, 21]. …”

The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria

“…KpnEF, an SMR pump, contributes to MDR and may be important in the infection process, because its expression is regulated by the Cpx regulatory system, which also affects capsule production (163). Inactivation of the MFS-type KpnGH pump results in 4-to 10-fold MIC reductions of the thirdand fourth-generation cephalosporins, spectinomycin, streptomycin, and tetracycline (307).…”

Macrolide resistance mechanisms inEnterobacteriaceae: Focus on azithromycin

“…: proposed association. a Homologs of some of these efflux pumps are present in other Enterobacteriaceae, such as AcrAB-TolC which is present in almost all Enterobacteriaceae, or KpnGH or KdeA which are the EmrAB and MdtA homologs in Klebsiella pneumoniae (Srinivasan et al, 2014). In these cases only the microorganism type is indicated.…”