Chapter 22 : Macrolide, Quinolone, and Other Non-β-Lactam Antibiotic Resistance in

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The emergence of resistance to penicillin and other beta-lactam antibiotics in pneumococci in the 1980s and 1990s led to the increased use of macrolides, fluoroquinolones, and other nonbetalactam antibiotics for pneumococcal infections. This chapter focuses on the molecular mechanisms of non-beta-lactam resistance in . Resistance to macrolides can occur by enzymatic inactivation, modification of the target by methylation or mutation, and active efflux. Proteins of the ABC transporter superfamily are organized such that two ATP-binding domains located cytoplasmically interact with two hydrophobic domains consisting of six to eight transmembrane domains. The esterase activity identified in hydrolyzed 14- and 16-membered macrolides. The primary targets of other quinolones have been determined; trovafloxacin, levofloxacin, and norfloxacin target topoisomerase IV (ParC), whereas the primary target of gatifloxacin is DNA gyrase (GyrA). The use of fluoroquinolones to treat pneumococcal infections is the most important factor in the emergence of fluoroquinolone resistance in . Inducible expression allows the mRNA to be made in an inactive conformation that becomes active by the presence of an inducing macrolide. In the United States, population-based surveillance for invasive disease showed that the rapid increase in macrolide resistance was correlated with the spread of mega in pneumococci. Exciting, recent data indicate that the total burden of antimicrobial resistance can be reduced by the use of pneumococcal conjugate vaccines that reduce colonization and transmission of the vaccine serotypes.

Citation: Ambrose K, Stephens D. 2004. Macrolide, Quinolone, and Other Non-β-Lactam Antibiotic Resistance in , p 350-366. In Tuomanen E, Mitchell T, Morrison D, Spratt B (ed), The Pneumococcus. ASM Press, Washington, DC. doi: 10.1128/9781555816537.ch22
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1. Ackermann, G.,, and A. C. Rodloff. 2003. Drugs of the 21st century: telithromycin (HMR 3647)—the first ketolide. J. Antimicrob. Chemother. 51: 497 511.
2. Adrian, P. V.,, and K. P. Klugman. 1997. Mutations in the dihydrofolate reductase gene of trimethoprim-resistant isolates of Streptococcus pneumoniae. Antimicrob. Agents Chemother. 41: 2406 2413.
3. Anderson, V. E.,, T. D. Gootz,, and N. Osheroff. 1998. Topoisomerase IV catalysis and the mechanism of quinolone action. J. Biol. Chem. 273: 17879 17885.
4. Ayoubi, P.,, A. O. Kilic,, and M. N. Vijayakumar. 1991. Tn 5253, the pneumococcal omega ( cat tet) BM6001 element, is a composite structure of two conjugative transposons, Tn 5251 and Tn 5252. J. Bacteriol. 173: 1617 1622.
5. Ballester, S.,, P. Lopez,, J. C. Alonso,, M. Espinosa,, and S. A. Lacks. 1986. Selective advantage of deletions enhancing chloramphenicol acetyltransferase gene expression in Streptococcus pneumoniae plasmids. Gene 41: 153 163.
6. Bast, D. J.,, J. C. de Azavedo,, T. Y. Tam,, L. Kilburn,, C. Duncan,, L. A. Mandell,, R. J. Davidson,, and D. E. Low. 2001. Interspecies recombination contributes minimally to fluoroquinolone resistance in Streptococcus pneumoniae. Antimicrob. Agents Chemother. 45: 2631 2634.
7. Betriu, C.,, M. Redondo,, M. L. Palau,, A. Sanchez,, M. Gomez,, E. Culebras,, A. Boloix,, and J. J. Picazo. 2000. Comparative in vitro activities of linezolid, quinupristin-dalfopristin, moxifloxacin, and trovafloxacin against erythromycin-susceptible and -resistant streptococci. Antimicrob. Agents Chemother. 44: 1838 1841.
8. Black, S.,, and H. Shinefield. 1997. Issues and challenges: pneumococcal vaccination in pediatrics. Pediatr. Ann. 26: 355 60.
9. Breiman, R. F.,, J. C. Butler,, F. C. Tenover,, J. A. Elliott,, and R. R. Facklam. 1994. Emergence of drug-resistant pneumococcal infections in the United States. JAMA 271: 1831 1835.
10. Brenwald, N. P.,, M. J. Gill,, and R. Wise. 1998. Prevalence of a putative efflux mechanism among fluoroquinolone-resistant clinical isolates of Streptococcus pneumoniae. Antimicrob. Agents Chemother. 42: 2032 2035.
11. Brumfitt, W.,, and J. M. Hamilton-Miller. 1993. Reassessment of the rationale for the combinations of sulphonamides with diaminopyrimidines. J. Chemother. 5: 465 469.
12. Canu, A.,, B. Malbruny,, M. Coquemont,, T. A. Davies,, P. C. Appelbaum,, and R. Leclercq. 2002. Diversity of ribosomal mutations conferring resistance to macrolides, clindamycin, streptogramin, and telithromycin in Streptococcus pneumoniae. Antimicrob. Agents Chemother. 46: 125 131.
13. Centers for Disease Control and Prevention. 2001. Resistance of Streptococcus pneumoniae to fluoroquinolones— United States, 1995-1999. Morb. Mortal. Wkly. Rep. 50: 800804.
14. Chen, D. K.,, A. McGeer,, J. C. de Azavedo,, D. E. Low, and Canadian Bacterial Surveillance Network. 1999. Decreased susceptibility of Streptococcus pneumoniae to fluoroquinolones in Canada. N. Engl. J. Med. 341: 233 239.
15. Chopra, I.,, and M. Roberts. 2001. Tetracycline antibiotics: mode of action, applications, molecular biology, and epidemiology of bacterial resistance. Microbiol. Mol. Biol. Rev. 65: 232 260.
16. Clancy, J.,, J. Petitpas,, F. Dib-Hajj,, W. Yuan,, M. Cronan,, A. V. Kamath,, J. Bergeron,, and J. A. Retsema. 1996. Molecular cloning and functional analysis of a novel macrolide-resistance determinant, mefA, from Streptococcus pyogenes. Mol. Microbiol. 22: 867 879.
17. Clewell, D. B.,, S. E. Flannagan,, Y. Ike,, J. M. Jones,, and C. Gawron-Burke. 1988. Sequence analysis of termini of conjugative transposon Tn 916. J. Bacteriol. 170: 3046 3052.
18. Clewell, D. B.,, S. E. Flannagan,, and D. D. Jaworski. 1995. Unconstrained bacterial promiscuity: the Tn 916-Tn 1545 family of conjugative transposons. Trends Microbiol. 3: 229 236.
19. Clewell, D. B.,, and C. Gawron-Burke. 1986. Conjugative transposons and the dissemination of antibiotic resistance in streptococci. Annu. Rev. Microbiol. 40: 635 659.
20. Dagan, R.,, R. Melamed,, M. Muallem,, L. Piglansky,, D. Greenberg,, O. Abramson,, P. M. Mendelman,, N. Bohidar,, and P. Yagupsky. 1996. Reduction of nasopharyngeal carriage of pneumococci during the second year of life by a heptavalent conjugate pneumococcal vaccine. J. Infect. Dis. 174: 1271 1278.
21. David, F.,, G. de Cespedes,, F. Delbos,, and T. Horaud. 1993. Diversity of chromosomal genetic elements and gene identification in antibiotic- resistant strains of Streptococcus pneumoniae and Streptococcus bovis. Plasmid 29: 147 153.
22. Del Grosso, M.,, F. Iannelli,, C. Messina,, M. Santagati,, N. Petrosillo,, S. Stefani,, G. Pozzi,, and A. Pantosti. 2002. Macrolide efflux genes mef (A) and mef (E) are carried by different genetic elements in Streptococcus pneumoniae. J. Clin. Microbiol. 40: 774 778.
23. Depardieu, F.,, and P. Courvalin. 2001. Mutation in 23S rRNA responsible for resistance to 16-membered macrolides and streptogramins in Streptococcus pneumoniae. Antimicrob. Agents Chemother. 45: 319 323.
24. Doern, G. V. 2001. Antimicrobial use and the emergence of antimicrobial resistance with Streptococcus pneumoniae in the United States. Clin. Infect. Dis. 33( Suppl. 3): S187 S192.
25. Doern, G. V.,, A. Brueggemann,, H. P. Holley, Jr.,, and A. M. Rauch. 1996. Antimicrobial resistance of Streptococcus pneumoniae recovered from outpatients in the United States during the winter months of 1994 to 1995: results of a 30- center national surveillance study. Antimicrob. Agents Chemother. 40: 1208 1213.
26. Doern, G. V.,, K. P. Heilmann,, H. K. Huynh,, P. R. Rhomberg,, S. L. Coffman,, and A. B. Brueggemann. 2001. Antimicrobial resistance among clinical isolates of Streptococcus pneumoniae in the United States during 1999-2000, including a comparison of resistance rates since 1994-1995. Antimicrob. Agents Chemother. 45: 1721 1729.
27. Doherty, N.,, K. Trzcinski,, P. Pickerill,, P. Zawadzki,, and C. G. Dowson. 2000. Genetic diversity of the tet (M) gene in tetracycline- resistant clonal lineages of Streptococcus pneumoniae. Antimicrob. Agents Chemother. 44: 2979 2984.
28. Dowson, C. G.,, T. J. Coffey,, and B. G. Spratt. 1994. Origin and molecular epidemiology of penicillin-binding-protein-mediated resistance to beta-lactam antibiotics. Trends Microbiol. 2: 361 366.
29. Eliopoulos, G. M. 2003. Quinupristin-dalfopristin and linezolid: evidence and opinion. Clin. Infect. Dis. 36: 473 481.
30. Enright, M.,, P. Zawadski,, P. Pickerill,, and C. G. Dowson. 1998. Molecular evolution of rifampicin resistance in Streptococcus pneumoniae. Microb. Drug Resist. 4: 65 70.
31. Flannagan, S. E.,, L. A. Zitzow,, Y. A. Su,, and D. B. Clewell. 1994. Nucleotide sequence of the 18-kb conjugative transposon Tn 916 from Enterococcus faecalis. Plasmid 32: 350 354.
32. Fogarty, C. M.,, S. Kohno,, P. Buchanan,, M. Aubier,, and M. Baz. 2003. Communityacquired respiratory tract infections caused by resistant pneumococci: clinical and bacteriological efficacy of the ketolide telithromycin. J. Antimicrob. Chemother. 51: 947 955.
33. Franke, A. E.,, and D. B. Clewell. 1981. Evidence for a chromosome-borne resistance transposon (Tn 916) in Streptococcus faecalis that is capable of “conjugal” transfer in the absence of a conjugative plasmid. J. Bacteriol. 145: 494 502.
34. Fukuda, H.,, and K. Hiramatsu. 1999. Primary targets of fluoroquinolones in Streptococcus pneumoniae. Antimicrob. Agents Chemother. 43: 410 412.
35. Gay, K.,, W. Baughman,, Y. Miller,, D. Jackson,, C. G. Whitney,, A. Schuchat,, M. M. Farley,, F. Tenover,, and D. S. Stephens. 2000. The emergence of Streptococcus pneumoniae resistant to macrolide antimicrobial agents: a 6- year population-based assessment. J. Infect. Dis. 182: 1417 1424.
36. Gay, K.,, and D. S. Stephens. 2001. Structure and dissemination of a chromosomal insertion element encoding macrolide efflux in Streptococcus pneumoniae. J. Infect. Dis. 184: 56 65.
37. Gill, M. J.,, N. P. Brenwald,, and R. Wise. 1999. Identification of an efflux pump gene, pmrA, associated with fluoroquinolone resistance in Streptococcus pneumoniae. Antimicrob. Agents Chemother. 43: 187 189.
38. Goldstein, E. J.,, and S. M. Garabedian-Ruffalo. 2002. Widespread use of fluoroquinolones versus emerging resistance in pneumococci. Clin. Infect. Dis. 35: 1505 1511.
39. Gonzales, R.,, J. F. Steiner,, A. Lum,, and P. H. Barrett, Jr. 1999. Decreasing antibiotic use in ambulatory practice: impact of a multidimensional intervention on the treatment of uncomplicated acute bronchitis in adults. JAMA 281: 1512 1519.
40. Gordon, K. A.,, M. L. Beach,, D. J. Biedenbach,, R. N. Jones,, P. R. Rhomberg,, and A. H. Mutnick. 2002. Antimicrobial susceptibility patterns of beta-hemolytic and viridans group streptococci: report from the SENTRY Antimicrobial Surveillance Program (1997-2000). Diagn. Microbiol. Infect. Dis. 43: 157 162.
41. Horinouchi, S.,, and B. Weisblum. 1982. Nucleotide sequence and functional map of pC194, a plasmid that specifies inducible chloramphenicol resistance. J. Bacteriol. 150: 815 825.
42. Hyde, T. B.,, K. Gay,, D. S. Stephens,, D. J. Vugia,, M. Pass,, S. Johnson,, N. L. Barrett,, W. Schaffner,, P. R. Cieslak,, P. S. Maupin,, E. R. Zell,, J. H. Jorgensen,, R. R. Facklam,, and C. G. Whitney. 2001. Macrolide resistance among invasive Streptococcus pneumoniae isolates. JAMA 286: 1857 1862.
43. Johnston, N. J.,, J. C. De Azavedo,, J. D. Kellner,, and D. E. Low. 1998. Prevalence and characterization of the mechanisms of macrolide, lincosamide, and streptogramin resistance in isolates of Streptococcus pneumoniae. Antimicrob. Agents Chemother. 42: 2425 2426.
44. Jones, R. N.,, D. J. Farrell,, and I. Morrissey. 2003. Quinupristin-dalfopristin resistance in Streptococcus pneumoniae: novel L22 ribosomal protein mutation in two clinical isolates from the SENTRY Antimicrobial Surveillance Program. Antimicrob. Agents Chemother. 47: 2696 2698.
45. Kilic, A. O.,, M. N. Vijayakumar,, and S. F. al-Khaldi. 1994. Identification and nucleotide sequence analysis of a transfer-related region in the streptococcal conjugative transposon Tn 5252. J. Bacteriol. 176: 5145 5150.
46. Kim, S.,, S. W. Lee,, E. C. Choi,, and S. Y. Choi. 2003. Aminoacyl-tRNA synthetases and their inhibitors as a novel family of antibiotics. Appl. Microbiol. Biotechnol. 61: 278 288.
47. Klugman, K. P. 1990. Pneumococcal resistance to antibiotics. Clin. Microbiol. Rev. 3: 171 196.
48. Klugman, K. P. 2003. The role of clonality in the global spread of fluoroquinolone-resistant bacteria. Clin. Infect. Dis. 36: 783 785.
49. Klugman, K. P. 2002. The successful clone: the vector of dissemination of resistance in Streptococcus pneumoniae. J. Antimicrob. Chemother. 50( Suppl. S2): 1 5.
50. Le Bouguenec, C.,, G. de Cespedes,, and T. Horaud. 1988. Molecular analysis of a composite chromosomal conjugative element (Tn 3701) of Streptococcus pyogenes. J. Bacteriol. 170: 3930 3936.
51. Le Bouguenec, C.,, G. de Cespedes,, and T. Horaud. 1990. Presence of chromosomal elements resembling the composite structure Tn 3701 in streptococci. J. Bacteriol. 172: 727 734.
52. Leclercq, R.,, and P. Courvalin. 1991. Bacterial resistance to macrolide, lincosamide, and streptogramin antibiotics by target modification. Antimicrob. Agents Chemother. 35: 1267 1272.
53. Leclercq, R.,, and P. Courvalin. 2002. Resistance to macrolides and related antibiotics in Streptococcus pneumoniae. A ntimicrob. Agents Chemother. 46: 2727 2734.
54. Linares, J.,, J. Garau,, C. Dominguez,, and J. L. Perez. 1983. Antibiotic resistance and serotypes of Streptococcus pneumoniae from patients with community-acquired pneumococcal disease. Antimicrob. Agents Chemother. 23: 545 547.
55. Linares, J.,, R. Pallares,, T. Alonso,, J. L. Perez,, J. Ayats,, F. Gudiol,, P. F. Viladrich,, and R. Martin. 1992. Trends in antimicrobial resistance of clinical isolates of Streptococcus pneumoniae in Bellvitge Hospital, Barcelona, Spain (1979-1990). Clin. Infect. Dis. 15: 99 105.
56. Lonks, J. R.,, J. Garau,, and A. A. Medeiros. 2002. Implications of antimicrobial resistance in the empirical treatment of community-acquired respiratory tract infections: the case of macrolides. J. Antimicrob. Chemother. 50(Suppl. S2): 87 92.
57. Luna, V. A.,, P. Coates,, E. A. Eady,, J. H. Cove,, T. T. Nguyen,, and M. C. Roberts. 1999. A variety of gram-positive bacteria carry mobile mef genes. J. Antimicrob. Chemother. 44: 9 25.
58. Luna, V. A.,, and M. C. Roberts. 1998. The presence of the tetO gene in a variety of tetracycline- resistant Streptococcus pneumoniae serotypes from Washington State. J. Antimicrob. Chemother. 42: 613 619.
59. Maskell, J. P.,, A. M. Sefton,, and L. M. Hall. 1997. Mechanism of sulfonamide resistance in clinical isolates of Streptococcus pneumoniae. Antimicrob. Agents Chemother. 41: 2121 2126.
60. Maskell, J. P.,, A. M. Sefton,, and L. M. Hall. 2001. Multiple mutations modulate the function of dihydrofolate reductase in trimethoprim-resistant Streptococcus pneumoniae. Antimicrob. Agents Chemother. 45: 1104 1108.
61. Matsuoka, M.,, K. Endou,, H. Kobayashi,, M. Inoue,, and Y. Nakajima. 1998. A plasmid that encodes three genes for resistance to macrolide antibiotics in Staphylococcus aureus. FEMS Microbiol. Lett. 167: 221 227.
62. Mbelle, N.,, R. E. Huebner,, A. D. Wasas,, A. Kimura,, I. Chang,, and K. P. Klugman. 1999. Immunogenicity and impact on nasopharyngeal carriage of a nonavalent pneumococcal conjugate vaccine. J. Infect. Dis. 180: 1171 1176.
63. McDougal, L. K.,, F. C. Tenover,, L. N. Lee,, J. K. Rasheed,, J. E. Patterson,, J. H. Jorgensen,, and D. J. LeBlanc. 1998. Detection of Tn 917-like sequences within a Tn 916-like conjugative transposon (Tn 3872) in erythromycinresistant isolates of Streptococcus pneumoniae. Antimicrob. Agents Chemother. 42: 2312 2318.
64. Monro, R. E.,, and K. A. Marcker. 1967. Ribosome- catalysed reaction of puromycin with a formylmethionine-containing oligonucleotide. J. Mol. Biol. 25: 347 350.
65. Monro, R. E.,, and D. Vazquez. 1967. Ribosome- catalysed peptidyl transfer: effects of some inhibitors of protein synthesis. J. Mol. Biol. 28: 161 165.
66. Munoz-Najar, U.,, and M. N. Vijayakumar. 1999. An operon that confers UV resistance by evoking the SOS mutagenic response in streptococcal conjugative transposon Tn 5252. J. Bacteriol. 181: 2782 2788.
67. Musher, D. M.,, M. E. Dowell,, V. D. Shortridge,, R. K. Flamm,, J. H. Jorgensen,, P. Le Magueres,, and K. L. Krause. 2002. Emergence of macrolide resistance during treatment of pneumococcal pneumonia. N. Engl. J. Med. 346: 630 631.
68. Nagai, K.,, P. C. Appelbaum,, T. A. Davies,, L. M. Kelly,, D. B. Hoellman,, A. T. Andrasevic,, L. Drukalska,, W. Hryniewicz,, M. R. Jacobs,, J. Kolman,, J. Miciuleviciene,, M. Pana,, L. Setchanova,, M. K. Thege,, H. Hupkova,, J. Trupl,, and P. Urbaskova. 2002. Susceptibilities to telithromycin and six other agents and prevalence of macrolide resistance due to L4 ribosomal protein mutation among 992 pneumococci from 10 Central and Eastern European countries. Antimicrob. Agents Chemother. 46: 371 377.
69. Norgren, M.,, and J. R. Scott. 1991. The presence of conjugative transposon Tn 916 in the recipient strain does not impede transfer of a second copy of the element. J. Bacteriol. 173: 319 324.
70. Oggioni, M. R.,, C. G. Dowson,, J. M. Smith,, R. Provvedi,, and G. Pozzi. 1996. The tetracycline resistance gene tet(M) exhibits mosaic structure. Plasmid 35: 156 163.
71. Oster, P.,, A. Zanchi,, S. Cresti,, M. Lattanzi,, F. Montagnani,, C. Cellesi,, and G. M. Rossolini. 1999. Patterns of macrolide resistance determinants among community-acquired Streptococcus pneumoniae isolates over a 5-year period of decreased macrolide susceptibility rates. Antimicrob. Agents Chemother. 43: 2510 2512.
72. Padayachee, T.,, and K. P. Klugman. 1999. Molecular basis of rifampin resistance in Streptococcus pneumoniae. Antimicrob. Agents Chemother. 43: 2361 2365.
73. Pan, X. S.,, and L. M. Fisher. 1997. Targeting of DNA gyrase in Streptococcus pneumoniae by sparfloxacin: selective targeting of gyrase or topoisomerase IV by quinolones. Antimicrob. Agents Chemother. 41: 471 474.
74. Pelton, S. I.,, R. Dagan,, B. M. Gaines,, K. P. Klugman,, D. Laufer,, K. O’Brien,, and H. J. Schmitt. 2003. Pneumococcal conjugate vaccines: proceedings from an Interactive Symposium at the 41st Interscience Conference on Antimicrobial Agents and Chemotherapy. Vaccine 21: 1562 1571.
75. Perez, J. L.,, J. Linares,, J. Bosch,, M. J. Lopez de Goicoechea,, and R. Martin. 1987. Antibiotic resistance of Streptococcus pneumoniae in childhood carriers. J. Antimicrob. Chemother. 19: 278 280.
76. Perkins, J. B.,, and P. J. Youngman. 1984. A physical and functional analysis of Tn 917, a Streptococcus transposon in the Tn 3 family that functions in Bacillus. Plasmid 12: 119 138.
77. Pestova, E.,, J. J. Millichap,, F. Siddiqui,, G. A. Noskin,, and L. R. Peterson. 2002. Non- PmrA-mediated multidrug resistance in Streptococcus pneumoniae. J. Antimicrob. Chemother. 49: 553 556.
78. Piddock, L. J.,, and M. M. Johnson. 2002. Accumulation of 10 fluoroquinolones by wildtype or efflux mutant Streptococcus pneumoniae. Antimicrob. Agents Chemother. 46: 813 820.
79. Poyart-Salmeron, C.,, P. Trieu-Cuot,, C. Carlier,, and P. Courvalin. 1991. Nucleotide sequences specific for Tn 1545-like conjugative transposons in pneumococci and staphylococci resistant to tetracycline. Antimicrob. Agents Chemother. 35: 1657 1660.
80. Pozzi, G.,, R. A. Musmanno,, E. A. Renzoni,, M. R. Oggioni,, and M. G. Cusi. 1988. Host-vector system for integration of recombinant DNA into chromosomes of transformable and nontransformable streptococci. J. Bacteriol. 170: 1969 1972.
81. Provvedi, R.,, R. Manganelli,, and G. Pozzi. 1996. Characterization of conjugative transposon Tn5251 of Streptococcus pneumoniae. FEMS Microbiol. Lett. 135: 231 236.
82. Reinert, R. R.,, A. Wild,, P. Appelbaum,, R. Lutticken,, M. Y. Cil,, and A. Al-Lahham. 2003. Ribosomal mutations conferring resistance to macrolides in Streptococcus pneumoniae clinical strains isolated in Germany. Antimicrob. Agents Chemother. 47: 2319 2322.
83. Rice, L. B. 2000. Bacterial monopolists: the bundling and dissemination of antimicrobial resistance genes in gram-positive bacteria. Clin. Infect. Dis. 31: 762 769.
84. Richter, S. S.,, K. P. Heilmann,, S. L. Coffman,, H. K. Huynh,, A. B. Brueggemann,, M. A. Pfaller,, and G. V. Doern. 2002. The molecular epidemiology of penicillin-resistant Streptococcus pneumoniae in the United States, 1994-2000. Clin. Infect. Dis. 34: 330 339.
85. Roberts, M. C.,, J. Sutcliffe,, P. Courvalin,, L. B. Jensen,, J. Rood,, and H. Seppala. 1999. Nomenclature for macrolide and macrolide-lincosamide- streptogramin B resistance determinants. Antimicrob. Agents Chemother. 43: 2823 2830.
86. Rosato, A.,, H. Vicarini,, and R. Leclercq. 1999. Inducible or constitutive expression of resistance in clinical isolates of streptococci and enterococci cross-resistant to erythromycin and lincomycin. J. Antimicrob. Chemother. 43: 559 562.
87. Ross, J. I.,, E. A. Eady,, J. H. Cove,, and S. Baumberg. 1995. Identification of a chromosomally encoded ABC-transport system with which the staphylococcal erythromycin exporter MsrA may interact. Gene 153: 93 98.
88. Ross, J. I.,, E. A. Eady,, J. H. Cove,, W. J. Cunliffe,, S. Baumberg,, and J. C. Wootton. 1990. Inducible erythromycin resistance in staphylococci is encoded by a member of the ATP-binding transport super-gene family. Mol. Microbiol. 4: 1207 1214.
89. Salyers, A. A.,, N. B. Shoemaker,, A. M. Stevens,, and L. Y. Li. 1995. Conjugative transposons: an unusual and diverse set of integrated gene transfer elements. Microbiol. Rev. 59: 579 590.
90. Santagati, M.,, F. Iannelli,, M. R. Oggioni,, S. Stefani,, and G. Pozzi. 2000. Characterization of a genetic element carrying the macrolide efflux gene mef(A) in Streptococcus pneumoniae. Antimicrob. Agents Chemother. 44: 2585 2587.
91. Schimmel, P.,, J. Tao,, and J. Hill. 1998. Aminoacyl tRNA synthetases as targets for new anti-infectives. FASEB J. 12: 1599 1609.
92. Schlunzen, F.,, R. Zarivach,, J. Harms,, A. Bashan,, A. Tocilj,, R. Albrecht,, A. Yonath,, and F. Franceschi. 2001. Structural basis for the interaction of antibiotics with the peptidyl transferase centre in eubacteria. Nature 413: 814 821.
93. Schmitz, F. J.,, P. G. Higgins,, S. Mayer,, A. C. Fluit,, and A. Dalhoff. 2002. Activity of quinolones against gram-positive cocci: mechanisms of drug action and bacterial resistance. Eur. J. Clin. Microbiol. Infect. Dis. 21: 647 659.
94. Schmitz, F. J.,, M. Perdikouli,, A. Beeck,, J. Verhoef,, and A. C. Fluit. 2001. Molecular surveillance of macrolide, tetracycline and quinolone resistance mechanisms in 1191 clinical European Streptococcus pneumoniae isolates. Int. J. Antimicrob. Agents 18: 433 436.
95. Schrag, S. J.,, B. Beall,, and S. F. Dowell. 2000. Limiting the spread of resistant pneumococci: biological and epidemiologic evidence for the effectiveness of alternative interventions. Clin. Microbiol. Rev. 13: 588 601.
96. Scott, J. R.,, P. A. Kirchman,, and M. G. Caparon. 1988. An intermediate in transposition of the conjugative transposon Tn916. Proc. Natl. Acad. Sci. USA 85: 4809 4813.
97. Seppala, H.,, T. Klaukka,, J. Vuopio-Varkila,, A. Muotiala,, H. Helenius,, K. Lager,, P. Huovinen, and The Finnish Study Group for Antimicrobial Resistance. 1997. The effect of changes in the consumption of macrolide antibiotics on erythromycin resistance in group A streptococci in Finland. N. Engl. J. Med. 337: 441 446.
98. Sessegolo, J. F.,, A. S. Levin,, C. E. Levy,, M. Asensi,, R. R. Facklam,, and L. M. Teixeira. 1994. Distribution of serotypes and antimicrobial resistance of Streptococcus pneumoniae strains isolated in Brazil from 1988 to 1992. J. Clin. Microbiol. 32: 906 911.
99. Shaw, J. H.,, and D. B. Clewell. 1985. Complete nucleotide sequence of macrolide-lincosamide- streptogramin B-resistance transposon Tn 917 in Streptococcus faecalis. J. Bacteriol. 164: 782 796.
100. Shaw, W. V.,, and A. G. Leslie. 1991. Chloramphenicol acetyltransferase. Annu. Rev. Biophys. Biophys. Chem. 20: 363 386.
101. Shoemaker, N. B.,, M. D. Smith,, and W. R. Guild. 1980. DNase-resistant transfer of chromosomal cat and tet insertions by filter mating in Pneumococcus. Plasmid 3: 80 87.
102. Spika, J. S.,, R. R. Facklam,, B. D. Plikaytis,, M. J. Oxtoby, and The Pneumococcal Surveillance Working Group. 1991. Antimicrobial resistance of Streptococcus pneumoniae in the United States, 1979-1987. J. Infect. Dis. 163: 1273 1278.
103. Sutcliffe, J.,, A. Tait-Kamradt,, and L. Wondrack. 1996. Streptococcus pneumoniae and Streptococcus pyogenes resistant to macrolides but sensitive to clindamycin: a common resistance pattern mediated by an efflux system. Antimicrob. Agents Chemother. 40: 1817 1824.
104. Swartley, J. S.,, C. F. McAllister,, R. A. Hajjeh,, D. W. Heinrich,, and D. S. Stephens. 1993. Deletions of Tn 916-like transposons are implicated in tetM-mediated resistance in pathogenic Neisseria. Mol. Microbiol. 10: 299 310.
105. Syrogiannopoulos, G. A.,, I. N. Grivea,, A. Tait-Kamradt,, G. D. Katopodis,, N. G. Beratis,, J. Sutcliffe,, P. C. Appelbaum,, and T. A. Davies. 2001. Identification of an erm(A) erythromycin resistance methylase gene in Streptococcus pneumoniae isolated in Greece. Antimicrob. Agents Chemother. 45: 342 344.
106. Tait-Kamradt, A.,, J. Clancy,, M. Cronan,, F. Dib-Hajj,, L. Wondrack,, W. Yuan,, and J. Sutcliffe. 1997. mefE is necessary for the erythromycin- resistant M phenotype in Streptococcus pneumoniae. Antimicrob. Agents Chemother. 41: 2251 2255.
107. Tait-Kamradt, A.,, T. Davies,, P. C. Appelbaum,, F. Depardieu,, P. Courvalin,, J. Petitpas,, L. Wondrack,, A. Walker,, M. R. Jacobs,, and J. Sutcliffe. 2000. Two new mechanisms of macrolide resistance in clinical strains of Streptococcus pneumoniae from Eastern Europe and North America. Antimicrob. Agents Chemother. 44: 3395 3401.
108. Tait-Kamradt, A.,, T. Davies,, M. Cronan,, M. R. Jacobs,, P. C. Appelbaum,, and J. Sutcliffe. 2000. Mutations in 23S rRNA and ribosomal protein L4 account for resistance in pneumococcal strains selected in vitro by macrolide passage. Antimicrob. Agents Chemother. 44: 2118 2125.
109. Tomich, P. K.,, F. Y. An,, and D. B. Clewell. 1980. Properties of erythromycin-inducible transposon Tn 917 in Streptococcus faecalis. J. Bacteriol. 141: 1366 1374.
110. Tomich, P. K.,, F. Y. An,, and D. B. Clewell. 1979. A transposon (Tn 917) in Streptococcus faecalis that exhibits enhanced transposition during induction of drug resistance. Cold Spring Harbor Symp. Quant. Biol. 43(Pt. 2): 1217 1221.
111. van Tilburg, P. M.,, D. Bogaert,, M. Sluijter,, A. R. Jansz,, R. de Groot,, and P. W. Hermans. 2001. Emergence of rifampin-resistant Streptococcus pneumoniae as a result of antimicrobial therapy for penicillin-resistant strains. Clin. Infect. Dis. 33: e93 e96.
112. Vijayakumar, M. N.,, S. D. Priebe,, and W. R. Guild. 1986. Structure of a conjugative element in Streptococcus pneumoniae. J. Bacteriol. 166: 978 984.
113. Weisblum, B. 1995. Erythromycin resistance by ribosome modification. Antimicrob. Agents Chemother. 39: 577 585.
114. Weisblum, B. 1995. Insights into erythromycin action from studies of its activity as inducer of resistance. Antimicrob. Agents Chemother. 39: 797 805.
115. Whitney, C. G.,, M. M. Farley,, J. Hadler,, L. H. Harrison,, N. M. Bennett,, R. Lynfield,, A. Reingold,, P. R. Cieslak,, T. Pilishvili,, D. Jackson,, R. R. Facklam,, J. H. Jorgensen,, and A. Schuchat. 2003. Decline in invasive pneumococcal disease after the introduction of protein-polysaccharide conjugate vaccine. N. Engl. J. Med. 348: 1737 1746.
116. Whitney, C. G.,, M. M. Farley,, J. Hadler,, L. H. Harrison,, C. Lexau,, A. Reingold,, L. Lefkowitz,, P. R. Cieslak,, M. Cetron,, E. R. Zell,, J. H. Jorgensen,, and A. Schuchat. 2000. Increasing prevalence of multidrug-resistant Streptococcus pneumoniae in the United States. N. Engl. J. Med 343: 1917 1924.
117. Widdowson, C. A.,, P. V. Adrian,, and K. P. Klugman. 2000. Acquisition of chloramphenicol resistance by the linearization and integration of the entire staphylococcal plasmid pC194 into the chromosome of Streptococcus pneumoniae. Antimicrob. Agents Chemother. 44: 393 395.
118. Widdowson, C. A.,, and K. P. Klugman. 1999. Molecular mechanisms of resistance to commonly used non-betalactam drugs in Streptococcus pneumoniae. Semin. Respir. Infect. 14: 255 268.
119. Widdowson, C. A.,, and K. P. Klugman. 1998. The molecular mechanisms of tetracycline resistance in the pneumococcus. Microb. Drug Resist. 4: 79 84.
120. Widdowson, C. A.,, K. P. Klugman,, and D. Hanslo. 1996. Identification of the tetracycline resistance gene, tet(O), in Streptococcus pneumoniae. Antimicrob. Agents Chemother. 40: 2891 2893.
121. Wu, S. W.,, H. de Lencastre,, and A. Tomasz. 1999. The Staphylococcus aureus transposon Tn 551: complete nucleotide sequence and transcriptional analysis of the expression of the erythromycin resistance gene. Microb. Drug Resist. 5: 1 7.
122. Zeller, V.,, C. Janoir,, M. D. Kitzis,, L. Gutmann,, and N. J. Moreau. 1997. Active efflux as a mechanism of resistance to ciprofloxacin in Streptococcus pneumoniae. Antimicrob. Agents Chemother. 41: 1973 1978.


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Molecular mechanisms of antibiotic resistance in

Citation: Ambrose K, Stephens D. 2004. Macrolide, Quinolone, and Other Non-β-Lactam Antibiotic Resistance in , p 350-366. In Tuomanen E, Mitchell T, Morrison D, Spratt B (ed), The Pneumococcus. ASM Press, Washington, DC. doi: 10.1128/9781555816537.ch22
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Genetic bases for antibiotic resistance in pneumococci

Citation: Ambrose K, Stephens D. 2004. Macrolide, Quinolone, and Other Non-β-Lactam Antibiotic Resistance in , p 350-366. In Tuomanen E, Mitchell T, Morrison D, Spratt B (ed), The Pneumococcus. ASM Press, Washington, DC. doi: 10.1128/9781555816537.ch22

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