Role of novel multidrug efflux pump involved in drug resistance in Klebsiella pneumoniae

• Published in: PloS one 2014-05, Vol.9 (5), p.e96288-e96288
• Main Authors: Srinivasan, Vijaya Bharathi, Singh, Bharat Bhushan, Priyadarshi, Nitesh, Chauhan, Neeraj Kumar, Rajamohan, Govindan
• Format: Article
• Language: English
• Subjects: Acinetobacter baumannii; Acriflavine; Anti-Bacterial Agents - pharmacology; Antibiotics; Antimicrobial agents; Antimicrobial resistance; Azithromycin; Bacterial Proteins - genetics; Benzalkonium chloride; Biology and Life Sciences; Ceftazidime; Cell division; Chlorhexidine; Chlorides; Ciprofloxacin; Cloning; Councils; Deactivation; Deoxyribonucleic acid; Detergents; Disinfectants; Disinfection & disinfectants; DNA; Drug resistance; Drug Resistance, Multiple, Bacterial - genetics; E coli; Efflux; Ertapenem; Erythromycin; Escherichia coli; Ethidium bromide; Extrusion; Genes; Genes, MDR - physiology; Genomes; Gentamicin; Imipenem; Inactivation; Kinases; Klebsiella; Klebsiella pneumoniae; Klebsiella pneumoniae - drug effects; Klebsiella pneumoniae - genetics; Laboratories; Medicine and Health Sciences; Membrane Transport Proteins - genetics; Microbial Sensitivity Tests; Multidrug resistance; Norfloxacin; Nucleotide sequence; Physiology; Piperacillin; Plasmids; Proteins; Salmonella; Salmonella Typhimurium; Signal transduction; Sodium; Sodium dodecyl sulfate; Sodium lauryl sulfate; Spectinomycin; Staphylococcus aureus; Streptomycin; Substrates
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0096288

Multidrug 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. Insertional 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. The MFS efflux pump KpnGH involves in crucial physiological functions besides being an intrinsic resistance determinant in K. pneumoniae.