Multidrag Resistance

Currently, five different molecular classes of mdr efflux pumps are known [5], While pumps of the the ATP-binding cassette (ABC) transporter superfamily are driven by ATP hydrolysis, the other four superfamilies called resistance-nodulation-division (RND), major facilitator superfamily (MFS), multidrug and toxic compound extrusion (MATE), and small multidrag resistance transporter (SMR) are driven by the proton-motive force across the cytoplasmic membrane. Usually a single pump protein is located within the cytoplasmic membrane. However, the RND-type pumps which are restricted to Gram-negative bacteria consist of two additional components, a periplasmic membrane fusion protein (MFP) which connects the efflux pump to an outer... 

Sarkadi B, Homolya L, Szakacs G et al (2006) Human multidrag resistance ABCB and ABCG transporters participation in a chemoimmunity defense system. Physiol Rev 86 1179-1236... 

Bakos E, Homolya L (2007) Portrait of multifaceted transporter, the multidrag resistance-associated protein 1 (MRP1/ABCC1). Pflugers Arch 453 621 641... 

Huisman, M. T., et al. Multidrag resistance protein 2 (MRP2) transports HIV protease inhibitors, and transport can be enhanced by other drags. AIDS 2002, 36, 2295-2301. 

Williams, G. C., et al. Direct Evidence that Saquinavir Is Transported by Multidrag Resistance-Associated Protein (MRP1) and Canalicular Multispecific Organic Anion Transporter (MRP2). Antimicrob. Agents Chemother. 2002, 46, 3456-3462. 

D.R. Johnson and C.D. Klaassen. Regulation of rat multidrag resistance protein 2 by classes of prototypical microsomal enzyme inducers that activate distinct transcription pathways. Toxicol Sci. 67 182-189 (2002). 

H.R. Kast, B. Goodwin, P.T. Tarr, S.A. Jones, A.M. Anisfeld, C.M. Stoltz, P. Tontonoz, S. Kliewer, T.M. Willson, and P.A. Edwards. Regulation of multidrag resistance-associated protein 2 (ABCC2) by the nuclear receptors pregnane X receptor, farnesoid X-activated receptor, and constitutive androstane receptor. J Biol Chem. 277 2908-2915 (2002). 

Chu M, Mierzwa R, Patel M, Jenkins J, Das P, Pramanik B, Chan T-M (2000) A Novel Eveminomicin Antibiotic Active Against Multidrag-Resistant Bacteria. Tetrahedron Lett 41 6689... 

Obritsch MD, Fish DN, MacLaren R, Jung R. Nosocomial infections due to multidrag-resistant Pseudomonas aeruginosa epidemiology and treatment options. Pharmacotherapy. 2005 25 1353-1364. 

Lang T, Hitzl M, Burk O, Mornhinweg E, Keil A, Kerb R, Klein K, Zanger UM, Eichelbaum M, Fromm MF. Genetic polymorphisms in the multidrag resistance-... 

Fredericks S, Moreton M, Reboux S, et al. Multidrag resistance gene-1 (MDR-1) haplotypes have a minor influence on tacrolimus dose requirements. Transplantation 2006 82(5) 705-708. 

Gottesman MM, Ling V. The molecular basis of multidrag resistance in cancer the early years of P-glycoprotein research. FEBS Lett. 2006 580 998-1009. 

Gottesman MM, Fojo T, Bates SE. Multidrag resistance in cancer role of ATP-dependent transporters. Nat. Rev. Cancer 2002 2 48-58. 

Lacroix EJ, Cloeckaert A, Grepinet O, Pinault C, Popoff MY, Waxin H, Pardon P. Salmonella typhimurium acrB-like gene identification and role in resistance to biliary salts and detergents and in murine infection. EEMS Microbiol. Lett. 1996 135 161-167. Colmer JA, Eralick JA, Hamood AN. Isolation and characterization of a putative multidrag resistance pump from Vibrio cholerae. Mol. Microbiol. 1998 27 63-72. 

Piddock LJ. Multidrag-resistance efflux pumps - not just for resistance. Nat. Rev. Microbiol. 2006 4 629-636. 

Rattan A, Kalia A, Ahmad N. Multidrag-resistant Mycobac- 37. terium tuberculosis molecular perspectives. Emerging Infect. Dis. 1998 4 195-209. 

Benzoylhosloppone inhibited the growth of the multidrag resistant strain K1 of Plasmodium falciparum in vitro with an ICso-value of 0.4 pg ml" (100). 

Cisternino, S., Rousselle. C., Dagenais, C.. and Scherrmann. J.C. (2001) Screening of multidrag-resistance sensitive drugs by in situ brain perfusion in P-glycoprotein-deficient mice. Phannaceutical Research. 18. 183-190. 

Which one of the following drags is most likely to be effective against multidrag-resistant strains of M tuberculosis, including those resistant to streptomycin ... 

Amikacin is indicated for treatment of tuberculosis suspected to be caused by streptomycin-resistant or multidrag-resistant mycobacterial strains. To avoid emergence of resistance, amikacin should always be used in combination drug regimens. 

Ototoxicity is characteristic of the aminoglycoside antibiotics. Many multidrag-resistant strains of mycobacteria remain susceptible to amikacin, and there is no cross-resistance with streptomycin. While disturbances of equilibrium may occur with overdosage, PAS does not cause hearing loss. The answer is (A). 

The effect of curcumin on apoptosis in multidmg-resistant cell lines has been reported. Piwocka et al. ° demonstrated that curcumin induced cell death in multidrag-resistant CEM(P-gp4) and LoVo(P-gp4) cells in a caspase-3-independent maimer. Mehta et al. also examined the antiproliferative effects of curcumin against multidrag-resistant (MDR) lines, which were found to be highly sensitive to curcumin. The growth-inhibitory effect of curcumin was time- and dose-dependent and was correlated with its inhibition of ornithine decarboxylase activity. Curcumin preferentially arrested cells in the G2/S phase of the cell cycle. 

Sarkadi B, Price EM, Boucher RC, German UA, Scarborough GA. Expression of the human multidrag resistance cDNA insect cells generates a high activity drug-stimulated membrane ATPase. J Biol Chem 1992 267 4854-4858. 

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