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Chapter 17 : Pursuing Drug-Resistant Bacteria

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Abstract:

The excitement of being on his own in research in Italy groomed the author for other research experiences. With Raymond, who became both mentor and friend, the author worked independently in the area of radiation genetics. During his hematology fellowship, he followed up some research that he had begun with Charlotte Friend, placing leukemic spleens subcutaneously back into leukemic mice and noting prolongation of their lives. Stemming from the author’s experience with Watanabe, he also investigated the ecology of drug resistance and resistance plasmids. Bacteria have responded to the widespread applications of antibiotics by finding ways to become resistant, insensitive to the killing effects of these powerful drugs. The overuse of antibacterial agents kills off susceptible bacteria, enabling competitor flora in the environment to proliferate and cause infection, as well as causing some bacteria to actually develop mutations conferring resistance. The author is a voice for the proper use of antibiotics, and carries the message around the globe that we must make peace with the bacteria.

Citation: Levy S. 2000. Pursuing Drug-Resistant Bacteria, p 127-137. In Atlas R (ed), Many Faces, Many Microbes. ASM Press, Washington, DC. doi: 10.1128/9781555818128.ch17

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Antibacterial Agents
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Microbial Ecology
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Bacterial Genetics
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Hepatitis B virus
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Citation: Levy S. 2000. Pursuing Drug-Resistant Bacteria, p 127-137. In Atlas R (ed), Many Faces, Many Microbes. ASM Press, Washington, DC. doi: 10.1128/9781555818128.ch17
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References

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1. Alekshun, M. N.,, and S. B. Levy. 1999. Characterization of MarR superrepressor mutants. J. Bacteriol. 181: 3303 3306.
2. Levy, S. B.,, L. M. McMurry,, T. M. Barbosa,, V. Burdett,, P. Courvalin,, W. Hillen,, M. C. Roberts,, J. I. Rood,, and D. E. Taylor. 1999. Nomenclature for new tetracycline resistance determinants. Antimicrob. Agents Chemother. 43: 1523 1524.
3. Nelson, M. L.,, and S. B. Levy. 1999. Reversal of tetracycline resistance mediated by different bacterial tetracycline resistance determinants by an inhibitor of the Tet(B) antiport protein. Antimicrob. Agents Chemother. 43: 1719 1724.
4. Levy, S. B. 1998. Multidrug resistance: a sign of the times. N. Engl. J. Med. 338: 1376 1378.
5. McMurry, L. M.,, M. Oethinger,, and S. B. Levy. 1998. Triclosan targets lipid synthesis. Nature 394: 531 532.
6. Levy, S. B. 1998. The challenge of antibiotic resistance. Sci. Am. 278: 46 53.
7. Moken, M. C.,, L. M. McMurry,, and S. B. Levy. 1997. Selection of multiple antibiotic resistant (Mar) mutants of Escherichia coli by using the disinfectant pine oil: roles of the mar and acrAB loci. Antimicrob. Agents Chemother. 41: 2770 2772.
8. Alekshun, M.,, and S. B. Levy. 1997. Regulation of chromosomally mediated multiple antibiotic resistance: the mar regulon. Antimicrob. Agents Chemother. 41: 2067 2075.
9. Draper, M. P.,, R. L. Martell,, and S. B. Levy. 1997. Active efflux of the free acid form of the fluorescent dye 2' ,7' -bis (2-carboxyethyl)-5(6)-carboxyfluorescein in multidrug-resistance-protein overexpressing murine and human leukemia cells. Eur. J. Biochem. 243: 219 224.
10. Modrak, D. E.,, M. P. Draper,, and S. B. Levy. 1997. Emergence of different mechanisms of resistance in the evolution of multidrug resistance in murine erythroleukemia cell lines. Biochem. Pharmacol. 54: 1297 1306.
11. Aldema, M. L.,, L. M. McMurry,, A. R. Walmsley,, and S. B. Levy. 1996. Purification of the Tn10-specified tetracycline efflux antiporter TetA in a native state as a polyhistidine fusion protein. Molec. Microb. 19: 187 195.
12. Levy, S. B. 1995. Antimicrobial resistance: a global perspective. Adv. Exper. Med. Biol. 390: 1 13.
13. Nelson, M. L.,, B. H. Park,, and S. B. Levy. 1994. Molecular requirements for the inhibition of the tetracycline antiport protein and the effect of potent inhibitors on growth of tetracycline resistant bacteria. J. Med. Chem. 37: 1355 1361.
14. Slapak, C. A.,, P. M. Fracasso,, R. L. Martell,, D. L. Toppmeyer,, J.-M. Lecerf,, and S. B. Levy. 1994. Overexpression of the multidrug resistance associated protein (MRP) gene in vincristine but not doxorubicin-selected multidrug resistant murine erythroleukemia cells. Cancer Res. 54: 5607 5613.
15. Levy, S. B. 1993. Confronting multidrug resistance. A role for each of us. JAMA 269: 1840 1842.
16. Cohen, S. P.,, H. Hachler,, and S. B. Levy. 1993. Genetic and functional analysis of the multiple antibiotic resistance ( mar) locus in Escherichia coli. J. Bacteriol. 175: 1484 1492.
17. Cohen, S. P.,, W. Yan,, and S. B. Levy. 1993. A multidrug resistance regulatory chromosomal locus is widespread among enteric bacteria. J. Infect. Dis. 168: 484 488.
18. Levy, S. B. 1992. The Antibiotic Paradox. How Miracle Drugs Are Destroying the Miracle. Plenum, New York, N.Y..
19. Levy, S. B. 1992. Active efflux mechanisms for antimicrobial resistance. Antimicrob. Agents Chemother. 36: 695 703.
20. Levy, S. B. 1990. Starting life resistance-free. N. Engl. J. Med. 323: 335 337.
21. Rubin, R. A.,, S. B. Levy,, R. L. Heinrikson,, and F. J. Kezdy. 1990. Gene duplication in the evolution of the two complementing domains of gram-negative tetracycline efflux proteins. Gene 87: 7 13.
22. Marshall, B. M.,, D. Petrowski,, and S. B. Levy. 1990. Inter- and intraspecies spread of E. coli in a farm environment in the absence of antibiotic usage. Proc. Natl. Acad. Sci USA 87: 6609 6613.
23. Cohen, S. P.,, D. C. Hooper,, J. S. Wolfson,, K. S. Souza,, L. M. McMurry,, and S. B. Levy. 1988. Endogenous active efflux of norfloxacin in susceptible Escherichia coli. Antimicrob. Agents Chemother. 32: 1187 1191.
24. Levy, S. B.,, B. Marshall,, S. Schluederberg,, D. Rowse,, and J. Davis. 1988. High frequency of antimicrobial resistance in human fecal flora. Antimicrob. Agents Chemother. 32: 1801 1806.
25. Levy, S. B.,, and R. P. Novick. 1986. Antibiotic Resistance Genes: Ecology, Transfer, and Expression. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY.
26. Rolland, R.,, G. Hausfater,, B. Marshall,, and S. B. Levy. 1985. Increased frequency of antibiotic resistant gut flora in wild baboons in contact with human refuse. Appl. Environ. Microbiol. 49: 791 794.
27. George, A. M.,, and S. B. Levy. 1983. A gene in the major co-transductional gap of the Escherichia coli K-12 linkage map required for the expression of chromosomal resistance to tetracycline, chloramphenicol and other antibiotics. J. Bacteriol. 155: 541 548.
28. Mendez, B.,, C. Tachibana,, and S. B. Levy. 1980. Heterogeneity of tetracycline resistance determinants. Plasmid 3: 99 108.
29. McMurry, L. M.,, R. Petrucci,, and S. B. Levy. 1980. Active efflux of tetracycline encoded by four genetically different tetracycline resistance determinants in E. coli. Proc. Natl. Acad. Sci. USA 77: 3974 3977.
30. Levy, S. B.,, B. Marshall,, A. Onderdonk,, and D. Rowse-Eagle. 1980. Survival of E. coli host-vector systems in the mammalian intestine. Science 209: 391 394.
31. Levy, S. B.,, G. B. FitzGerald,, and A. B. Macone. 1976. Changes in intestinal flora of farm personnel after introduction of tetracycline-supplemented feed on a farm. N. Engl. J. Med. 295: 583 588.
32. Levy, S. B.,, and L. McMurry. 1974. Detection of an inducible membrane protein associated with R-factor-mediated tetracycline resistance. Biochem. Biophys. Res. Comm. 56: 1060 1068.

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