"efflux pumps" by kedar ghimire
DESCRIPTION
Undergraduate Class presentationTRANSCRIPT
Current Topics of Molecular Life SciencesIOR- Prof. Dr. Matthias Ullrich
class presentationKedar Ghimire,
May 15, 2007
Efflux pumps • Efflux refers to the outward flow.
• Efflux pumps are protein transporters localized in the cell membrane.
• Active transport
• Found in bacteria as well as eukaryotes (Bambeke et. al,2000)
•Specific or non-specific
Major superfamilies in prokaryotes
•MF (major facilitator, >1000)
•MATE (multidrug and toxic efflux)
•RND (resistance- nodulation- division)
•SMR (small multi-drug resistance)
•ABC (ATP binding cassette), primary membrane transporter
glycerol-3-phosphate transporter
Diagrammatic representation of the membrane topology of drug transporters belonging to the ABC superfamily
Biochemical Journal Biochem. J. (2003) 376, 313-338
Resistance-nodulation-cell division transporter in E. Coli
http://opm.phar.umich.edu/?images=all
Antibiotic resistance: what is it?• One of the world's most pressing public health problems.
• Nearly all significant bacterial infections in the world are becoming resistant, genetic material clonal
http://www.public.asu.edu/~shaydel/personnel.html
Importance of efflux pumps in bacterial resistance
FINDINGS• not evolved in response to antibiotics
• Increased expression linked with resistance but is not the only factor • Intrinsic resistance of Gram-negative bacteria, e.g Pseudomonas aeruginosa
• Efflux pump inhibitors taken with antibiotics
• Fluoroquinolone-resistant strains of E coli have been seen selected over wildtype (1000 fold).
AcrAB-TolC
Importance of efflux pumps in bacterial resistance
•MICs of antibiotics seen increased •Cross resistance, all generationsof antibiotics effected- a problem
•Expression increases with stress. Over expression results from mutation or activation
•Unregulated overexpression is disadvantageous
Discussion and conclusion•Increasing evidence about role of efflux pumps in antibiotic resistance
•Efflux pumps possess significant structural homology
•Considerations for design of new drugs-structural alterations after entrance into the cell
•Careful inhibition of pumps necessary
•Researchers should be careful
Thank you all for your kind attention!! Reference
Francoise Van Bambeke, Elisabetta Balzi and Paul M. Tulkens (2000) Antibiotic Efflux Pumps, Biochemical Pharmacology, Vol. 60, pp. 457–470Satoshi Murakami, Ryosuke Nakashima, Eiki Yamashita & Akihito Yamaguchi(2002) Crystal structure of bacterial multidrug efflux transporter AcrB, Nature, 419(6907):587-93 Yafei Huang,M. Joanne Lemieux,Jinmei Song, Manfred Auer, Da-Neng Wang (2003), Structure and Mechanism of the Glycerol-3-Phosphate Transporter from Escherichia coli, Science, Vol 301Rungtip Chuanchuen et al.,(2001) Cross-Resistance between Triclosan and Antibiotics in Pseudomonas aeruginosa Is Mediated by Multidrug Efflux Pumps: Exposure of a Susceptible Mutant Strain to Triclosan Selects nfxB Mutants Overexpressing MexCD-OprJ, Antimicrobial Agents and Chemotherapy, p. 428-432 Waltzing transporters and the dance macabre’ between humans and bacteria(2007) Nature Reviews Drug Discovery, Decemberhttp://saturn.med.nyu.edu/research/sb/wanglab/index.htmlhttp://en.wikipedia.org/wiki/Effluxhttp://opm.phar.umich.edu/?images=allhttp://whyfiles.org/038badbugs/mechanism.htmlhttp://focosi.altervista.org/gram+-bacteria.jpghttp://www.biotechnologyonline.gov.au/popups/img_antibiotics.cfmhttp://www.nearingzero.net/natural/screenres/natural095.jpg