Chapter 17 : Pursuing Drug-Resistant Bacteria

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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

Key Concept Ranking

Antibacterial Agents
Microbial Ecology
Bacterial Genetics
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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1. Alekshun, M. N.,, and S. B. Levy. 1999. Characterization of MarR superrepressor mutants. J. Bacteriol. 181:33033306.
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. 43:15231524.
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. 43:17191724.
4. Levy, S. B. 1998. Multidrug resistance: a sign of the times. N. Engl. J. Med. 338:13761378.
5. McMurry, L. M.,, M. Oethinger,, and S. B. Levy. 1998. Triclosan targets lipid synthesis. Nature 394:531532.
6. Levy, S. B. 1998. The challenge of antibiotic resistance. Sci. Am. 278:4653.
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. 41:27702772.
8. Alekshun, M.,, and S. B. Levy. 1997. Regulation of chromosomally mediated multiple antibiotic resistance: the mar regulon. Antimicrob. Agents Chemother. 41:20672075.
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. 243:219224.
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. 54:12971306.
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. 19:187195.
12. Levy, S. B. 1995. Antimicrobial resistance: a global perspective. Adv. Exper. Med. Biol. 390:113.
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. 37:13551361.
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. 54:56075613.
15. Levy, S. B. 1993. Confronting multidrug resistance. A role for each of us. JAMA 269:18401842.
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. 175:14841492.
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. 168:484488.
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. 36:695703.
20. Levy, S. B. 1990. Starting life resistance-free. N. Engl. J. Med. 323:335337.
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 87:713.
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 87:66096613.
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. 32:11871191.
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. 32:18011806.
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. 49:791794.
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. 155:541548.
28. Mendez, B.,, C. Tachibana,, and S. B. Levy. 1980. Heterogeneity of tetracycline resistance determinants. Plasmid 3:99108.
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 77:39743977.
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 209:391394.
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. 295:583588.
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. 56:10601068.

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