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is the bacterial pathogen most frequently implicated in community-acquired respiratory tract infections (RTI) and also has the distinction of being the leading cause of invasive bacterial disease in the very young and the elderly. Aminoglycoside resistance in pneumococci is not usually reported in surveillance studies, largely because antibiotics from this class are rarely used to treat pneumococcal infections. Macrolides, lincosamides, and streptogramins, though chemically distinct, are usually considered together because they inhibit protein synthesis by binding to overlapping sites in the 50S bacterial ribosomal subunit. β-lactam antibiotics target one or more of the penicillin-binding proteins (PBPs) involved in a late step in peptidoglycan biosynthesis. Fluoroquinolones interact with eubacterial type 2 topoisomerases, DNA gyrase, and topoisomerase IV. Both of these enzymes are essential for DNA replication, and both function as tetrameric heterodimers (AB). DNA gyrase and topoisomerase IV are encoded by sets of homologous genes, and and and , respectively. Trimethoprim (TMP) is a diaminopyrimidine that selectively inhibits bacterial dihydrofolate reductase. Chloramphenicol is a small molecule that has been described as a structural analog of puromycin, an aminoacylated nucleoside. is an important community and hospital pathogen that is becoming increasingly multidrug resistant. For community-acquired respiratory tract infections, therapy is generally empiric and drugs are needed to cover the common clones that are becoming more difficult to treat. In invasive situations and even in very highly penicillin-resistant pneumococci, the use of conjugate vaccines has significantly lessened incidence in children.

Citation: Sutcliffe J, Roberts M. 2005. , p 314-329. In White D, Alekshun M, McDermott P (ed), Frontiers in Antimicrobial Resistance. ASM Press, Washington, DC. doi: 10.1128/9781555817572.ch23

Key Concept Ranking

Bacterial Diseases
Streptococcus pneumoniae
Type II DNA Topoisomerase
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1. Achari, A.,, D. O. Somers,, J. N. Champness,, P. K. Bryant,, J. Rosemond,, and D. K. Stammers. 1997. Crystal structure of the anti-bacterial sulfonamide drug target dihydropteroate synthase. Nat. Struct. Biol. 4:490497.
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. 41:24062413.
3.Antimicrobial Therapy, Inc. 2003. Clinical approach to initial choice of antimicrobial therapy, p. 5. In D. N. Gilbert,, R. C. Moellering, Jr.,, and M. A. Sande (ed.), The Sanford Guide to Antimicrobial Therapy, 33rd ed. Antimicrobial Therapy, Inc., Hyde Park, Vt.
4. Appelbaum, P. C. 1987. World-wide development of antibiotic resistance in pneumococci. Eur. J. Clin. Microbiol. 6:367377.
5. Ayoubi, P.,, A. O. Kilic,, and M. N. Vijayakumar. 1991. Tn5253, the pneumococcal omega (cat tet) BM6001 element, is a composite structure of two conjugative transposons, Tn5251 and Tn5252. J. Bacteriol. 173:16171622.
6. Baca, A. M.,, R. Sirawaraporn,, S. Turley,, W. Sirawaraporn,, and W. G. Hol. 2000. Crystal structure of Mycobacterium tuberculosis 7,8-dihydropteroate synthase in complex with pterin monophosphate: new insight into the enzymatic mechanism and sulfa-drug action. J. Mol. Biol. 302:11931212.
7. Banks, D. J.,, S. F. Porcella,, K. D. Barbian,, J. M. Martin,, and J. M. Musser. 2003. Structure and distribution of an unusual chimeric genetic element encoding macrolide resistance in phylogenetically diverse clones of group A Streptococcus. J. Infect. Dis. 188:18981908.
8. Bellon, S.,, J. D. Parsons,, Y. Wei,, K. Hayakawa,, L. L. Swenson,, P. S. Charifson,, J. A. Lippke,, R. Aldape,, and C. H. Gross. 2004. Crystal structures of Escherichia coli topoisomerase IV ParE subunit (24 and 43 kilodaltons): a single residue dictates differences in novobiocin potency against topoisomerase IV and DNA gyrase. Antimicrob. Agents Chemother. 48:18561864.
9. Berisio, R.,, J. Harms,, F. Schluenzen,, R. Zarivach,, H. A. Hansen,, P. Fucini,, and A. Yonath. 2003. Structural insight into the antibiotic action of telithromycin against resistant mutants. J. Bacteriol. 185:42764279.
10. Bolin, J. T.,, D. J. Filman,, D. A. Matthews,, R. C. Hamlin,, and J. Kraut. 1982. Crystal structures of Escherichia coli and Lactobacillus casei dihydrofolate reductase refined at 1.7 Å resolution. I. General features and binding of methotrexate. J. Biol. Chem. 257:1365013662.
11. Bozdogan, B.,, T. Bogdanovich,, K. Kosowska,, M. R. Jacobs,, and P. C. Appelbaum. 2004. Macrolide resistance in Streptococcus pneumoniae: clonality and mechanisms of resistance in 24 countries. Curr. Drug Topics—Infect. Disorders 4:169176.
12. Brenwald, N. P.,, P. Appelbaum,, T. Davies,, and M. J. Gill. 2003. Evidence for efflux pumps, other than PmrA, associated with fluoroquinolone resistance in Streptococcus pneumoniae. Clin. Microbiol. Infect. 9:140143.
13. 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. 42:20322035.
14. Brodersen, D. E.,, W. M. Clemons, Jr.,, A. P. Carter,, R. J. Morgan-Warren,, B. T. Wimberly,, and V. Ramakrishnan. 2000. The structural basis for the action of the antibiotics tetracycline, pactamycin, and hygromycin B on the 30S ribosomal subunit. Cell 103:11431154.
15. Brown, C. M.,, K. K. McCaughan,, and W. P. Tate. 1993. Two regions of the Escherichia coli 16S ribosomal RNA are important for decoding stop signals in polypeptide chain termination. Nucleic Acids Res. 21:21092115.
16. Brown, S. D.,, and M. J. Rybak. 2004. Antimicrobial susceptibility of Streptococcus pneumoniae, Streptococcus pyogenes and Haemophilus influenzae collected from patients across the USA, in 2001-2002, as part of the PROTEKT US study. J. Antimicrob. Chemother. 54 (Suppl 1.):I7I15.
17. Campbell, G. D., Jr.,, and R. Silberman. 1998. Drug-resistant Streptococcus pneumoniae. Clin. Infect. Dis. 26:11881195.
18. Canton, R.,, M. Morosini,, M. C. Enright,, and I. Morrissey. 2003. Worldwide incidence, molecular epidemiology and mutations implicated in fluoroquinolone-resistant Streptococcus pneumoniae: data from the global PROTEKT surveillance programme. J. Antimicrob. Chemother. 52:944952.
19. 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. 46:125131.
20. Carter, A. P.,, W. M. Clemons,, D. E. Brodersen,, R. J. Morgan- Warren,, B. T. Wimberly,, and V. Ramakrishnan. 2000. Functional insights from the structure of the 30S ribosomal subunit and its interactions with antibiotics. Nature 407:340348.
21. Chesnel, L.,, L. Pernot,, D. Lemaire,, D. Champelovier,, J. Croize,, O. Dideberg,, T. Vernet,, and A. Zapun. 2003. The structural modifications induced by the M339F substitution in PBP2x from Streptococcus pneumoniae further decreases the susceptibility to beta-lactams of resistant strains. J. Biol. Chem. 278:4444844456.
22. Chopra, I.,, and M. Roberts. 2001. Tetracycline antibiotics: mode of action, applications, molecular biology, and epidemiology of bacterial resistance. Microbiol. Mol. Biol. Rev. 65:232260.
23. 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. 22:867879.
24. Contreras, A.,, and D. Vazquez. 1977. Cooperative and antagonistic interactions of peptidyl-tRNA and antibiotics with bacterial ribosomes. Eur. J. Biochem. 74:539547.
25. Corbett, K. D.,, R. K. Shultzaberger,, and J. M. Berger. 2004. The C-terminal domain of DNA gyrase A adopts a DNAbending beta-pinwheel fold. Proc. Natl. Acad. Sci. USA 101: 72937298.
26. Cousin, S., Jr.,, W. L. Whittington,, and M. C. Roberts. 2003. Acquired macrolide resistance genes in pathogenic Neisseria spp. isolated between 1940 and 1987. Antimicrob. Agents Chemother. 47:38773880.
27. Daigle, D. M.,, G. A. McKay,, P. R. Thompson,, and G. D. Wright. 1999. Aminoglycoside antibiotic phosphotransferases are also serine protein kinases. Chem. Biol. 6:1118.
28. Daigle, D. M.,, G. A. McKay,, and G. D. Wright. 1997. Inhibition of aminoglycoside antibiotic resistance enzymes by protein kinase inhibitors. J. Biol. Chem. 272:2475524758.
29. Dale, G. E.,, D. Kostrewa,, B. Gsell,, M. Stieger,, and A. D’Arcy. 1999. Crystal engineering: deletion mutagenesis of the 24 kDa fragment of the DNA gyrase B subunit from Staphylococcus aureus. Acta Crystallogr. D. Biol. Crystallogr. 55 (Pt 9):16261629.
30. Daly, M. M.,, S. Doktor,, R. Flamm,, and D. Shortridge. 2004. Characterization and prevalence of MefA, MefE, and the associated msr(D) gene in Streptococcus pneumoniae clinical isolates. J. Clin. Microbiol. 42:35703574.
31. de Antonio, C.,, M. E. Farias,, M. G. de Lacoba,, and M. Espinosa. 2004. Features of the plasmid pMV158-encoded MobM, a protein involved in its mobilization. J. Mol. Biol. 335:733743.
32. Del Grosso, M.,, A. Scotto d’Abusco,, F. Iannelli,, G. Pozzi,, and A. Pantosti. 2004. Tn2009, a Tn916-like element containing mef(E) in Streptococcus pneumoniae. Antimicrob. Agents Chemother. 48:20372042.
33. Deshpande, L. M.,, R. N. Jones,, and M. A. Pfaller. 2001. Accuracy of broth microdilution and E test methods for detecting chloramphenicol acetyl transferase mediated resistance in Streptococcus pneumoniae: geographic variations in the prevalence of resistance in The SENTRY Antimicrobial Surveillance Program (1999). Diagn. Microbiol. Infect. Dis. 39:267269.
34. Dessen, A.,, N. Mouz,, E. Gordon,, J. Hopkins,, and O. Dideberg. 2001. Crystal structure of PBP2x from a highly penicillinresistant Streptococcus pneumoniae clinical isolate: a mosaic framework containing 83 mutations. J. Biol. Chem. 276: 4510645112.
35. Dever, L. L.,, K. Shashikumar,, and W. G. Johanson, Jr. 2002. Antibiotics in the treatment of acute exacerbations of chronic bronchitis. Expert Opin. Investig. Drugs 11:911925.
36. Doern, G. V.,, A. B. Brueggemann,, H. Huynh,, and E. Wingert. 1999. Antimicrobial resistance with Streptococcus pneumoniae in the United States, 1997-98. Emerg. Infect. Dis. 5:757765.
37. 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. 45:17211729.
38. Douthwaite, S.,, L. H. Hansen,, and P. Mauvais. 2000. Macrolide-ketolide inhibition of MLS-resistant ribosomes is improved by alternative drug interaction with domain II of 23S rRNA. Mol. Microbiol. 36:183193.
39. Dutta, R.,, and M. Inouye. 2000. GHKL, an emergent ATPase/kinase superfamily. Trends Biochem. Sci. 25:2428.
40. Epe, B.,, P. Woolley,, and H. Hornig. 1987. Competition between tetracycline and tRNA at both P and A sites of the ribosome of Escherichia coli. FEBS Lett. 213:443447.
41. Ettayebi, M.,, S. M. Prasad,, and E. A. Morgan. 1985. Chloramphenicol- erythromycin resistance mutations in a 23S rRNA gene of Escherichia coli. J. Bacteriol. 162:551557.
42. Farrell, D. J.,, I. Morrissey,, S. Bakker,, S. Buckridge,, and D. Felmingham. 2004. In vitro activity of telithromycin, linezolid and quinupristin-dalfopristin in Streptococcus pneumoniae with macrolide resistance due to ribosomal mutations. Antimicrob. Agents Chemother. 48:31693171.
43. Fernandez-Munoz, R.,, R. E. Monro,, R. Torres-Pinedo,, and D. Vazquez. 1971. Substrate- and antibiotic-binding sites at the peptidyl-transferase centre of Escherichia coli ribosomes. Studies on the chloramphenicol, lincomycin and erythromycin sites. Eur. J. Biochem. 23:185193.
44. Filman, D. J.,, J. T. Bolin,, D. A. Matthews,, and J. Kraut. 1982. Crystal structures of Escherichia coli and Lactobacillus casei dihydrofolate reductase refined at 1.7 Å resolution. II. Environment of bound NADPH and implications for catalysis. J. Biol. Chem. 257:1366313672.
45. Franceschi, F.,, Z. Kanyo,, E. C. Sherer,, and J. Sutcliffe. 2004. Macrolide resistance from the ribosome perspective. Curr. Drug Topics—Infect. Disorders 4:177191.
46. Friedland, I. R.,, and K. P. Klugman. 1992. Antibiotic-resistant pneumococcal disease in South African children. Am. J. Dis. Child 146:920923.
47. Garza-Ramos, G.,, L. Xiong,, P. Zhong,, and A. Mankin. 2001. Binding site of macrolide antibiotics on the ribosome: new resistance mutation identifies a specific interaction of ketolides with rRNA. J. Bacteriol. 183:68986907.
48. Gay, K.,, and D. S. Stephens. 2001. Structure and dissemination of a chromosomal insertion element encoding macrolide efflux in Streptococcus pneumoniae. J. Infect. Dis. 184:5665. Epub May 31, 2001.
49. 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. 43:187189.
50. Giovanetti, E.,, A. Brenciani,, R. Lupidi,, M. C. Roberts,, and P. E. Varaldo. 2003. Presence of the tet(O) gene in erythromycin- and tetracycline-resistant strains of Streptococcus pyogenes and linkage with either the mef(A) or the erm(A) gene. Antimicrob. Agents Chemother. 47:28442849.
51. Gordon, E.,, N. Mouz,, E. Duee,, and O. Dideberg. 2000. The crystal structure of the penicillin-binding protein 2x from Streptococcus pneumoniae and its acyl-enzyme form: implication in drug resistance. J. Mol. Biol. 299:477485.
52. Gosink, K.,, and E. Tuomanen,. 2000. Streptococcus pneumoniae: invasion and inflammation, p. 214224. In V. Fischetti (ed.), Gram-Positive Pathogens. ASM Press, Washington, D.C.
53. Gould, K. A.,, X. S. Pan,, R. J. Kerns,, and L. M. Fisher. 2004. Ciprofloxacin dimers target gyrase in Streptococcus pneumoniae. Antimicrob. Agents Chemother. 48:21082115.
54. Grebe, T.,, J. Paik,, and R. Hakenbeck. 1997. A novel resistance mechanism against beta-lactams in Streptococcus pneumoniae involves CpoA, a putative glycosyltransferase. J. Bacteriol. 179:33423349.
55. Gross, C. H.,, J. D. Parsons,, T. H. Grossman,, P. S. Charifson,, S. Bellon,, J. Jernee,, M. Dwyer,, S. P. Chambers,, W. Markland,, M. Botfield,, and S. A. Raybuck. 2003. Active-site residues of Escherichia coli DNA gyrase required in coupling ATP hydrolysis to DNA supercoiling and amino acid substitutions leading to novobiocin resistance. Antimicrob. Agents Chemother. 47:10371046.
56. Guenzi, E.,, A. M. Gasc,, M. A. Sicard,, and R. Hakenbeck. 1994.Atwo-component signal-transducing system is involved in competence and penicillin susceptibility in laboratory mutants of Streptococcus pneumoniae. Mol. Microbiol. 12:505515.
57. Haasum, Y.,, K. Strom,, R. Wehelie,, V. Luna,, M. C. Roberts,, J. P. Maskell,, L. M. Hall,, and G. Swedberg. 2001. Amino acid repetitions in the dihydropteroate synthase of Streptococcus pneumoniae lead to sulfonamide resistance with limited effects on substrate K(m). Antimicrob. Agents Chemother. 45:805809.
58. Hakenbeck, R.,, A. Konig,, I. Kern,, M. van der Linden,, W. Keck,, D. Billot-Klein,, R. Legrand,, B. Schoot,, and L. Gutmann. 1998. Acquisition of five high-Mr penicillin-binding protein variants during transfer of high-level beta-lactam resistance from Streptococcus mitis to Streptococcus pneumoniae. J. Bacteriol. 180:18311840.
59. Hampele, I. C.,, A. D’Arcy,, G. E. Dale,, D. Kostrewa,, J. Nielsen,, C. Oefner,, M. G. Page,, H. J. Schonfeld,, D. Stuber,, and R. L. Then. 1997. Structure and function of the dihydropteroate synthase from Staphylococcus aureus. J. Mol. Biol. 268:2130.
60. Hansen, H. L.,, P. Mauvais,, and S. Douthwaite. 1999. The macrolide-ketolide antibiotic binding site is formed by structures in domain II and V of 23S ribosomal RNA. Mol. Microbiol. 31:623631.
61. Hansen, J. L.,, J. A. Ippolito,, N. Ban,, P. Nissen,, P. B. Moore,, and T. A. Steitz. 2002. The structures of four macrolide antibiotics bound to the large ribosomal subunit. Mol. Cell. 10: 117128.
62. Hansen, J. L.,, P. B. Moore,, and T. A. Steitz. 2003. Structures of five antibiotics bound at the peptidyl transferase center of the large ribosomal subunit. J. Mol. Biol. 330:10611075.
63. Harms, J. M.,, F. Schlunzen,, P. Fucini,, H. Bartels,, and A. Yonath. 2004. Alterations at the peptidyl transferase centre of the ribosome induced by the synergistic action of the streptogramins dalfopristin and quinupristin. BMC Biol. 2:4.
64. Hennessy, T. W.,, K. M. Petersen,, D. Bruden,, A. J. Parkinson,, D. Hurlburt,, M. Getty,, B. Schwartz,, and J. C. Butler. 2002. Changes in antibiotic-prescribing practices and carriage of penicillin-resistant Streptococcus pneumoniae: a controlled intervention trial in rural Alaska. Clin. Infect. Dis. 34:15431550.
65. Hoban, D. J.,, G. V. Doern,, A. C. Fluit,, M. Roussel-Delvallez,, and R. N. Jones. 2001. Worldwide prevalence of antimicrobial resistance in Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in the SENTRY Antimicrobial Surveillance Program, 1997-1999. Clin. Infect. Dis. 32 (Suppl. 2):S81S93.
66. Hon, W. C.,, G. A. McKay,, P. R. Thompson,, R. M. Sweet,, D. S. Yang,, G. D. Wright,, and A. M. Berghuis. 1997. Structure of an enzyme required for aminoglycoside antibiotic resistance reveals homology to eukaryotic protein kinases. Cell 89:887895.
67. Hooper, D. C. 2000. Mechanisms of action and resistance of older and newer fluoroquinolones. Clin. Infect. Dis. 31 (Suppl. 2):S24S28.
68. Hooper, D. C., 2000. Mechanisms of fluoroquinolone resistance, p. 685693. In V. Fischetti (ed.), Gram-Positive Pathogens. ASM Press, Washington, D.C.
69. Hsieh, T. J.,, and N. L. Chan. 2004. Crystallization and preliminary X-ray crystallographic analysis of the C-terminal domain of ParC protein from Bacillus stearothermophilus. Acta Crystallogr. D. Biol. Crystallogr. 60:564566.
70. Iannelli, F.,, M. Santagati,, J. D. Doquier,, M. Cassone,, M. R. Oggioni,, G. Rossolini,, S. Stefani,, and G. Pozzi. 2004. Type M Resistance to macrolides in streptococci is not due to the mef(A) gene, but to mat(A) encoding an ATP-dependent efflux pump, abstr. C1-1188. Program and Abstracts of the 104th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, D.C.
71. Idanpaan-Heikkila, I.,, P. M. Simon,, D. Zopf,, T. Vullo,, P. Cahill,, K. Sokol,, and E. Tuomanen. 1997. Oligosaccharides interfere with the establishment and progression of experimental pneumococcal pneumonia. J. Infect. Dis. 176:704712.
72. Inoue, M.,, N. Y. Lee,, S. W. Hong,, K. Lee,, and D. Felmingham. 2004. PROTEKT 1999-2000: a multicentre study of the antibiotic susceptibility of respiratory tract pathogens in Hong Kong, Japan and South Korea. Int. J. Antimicrob. Agents 23:4451.
73. Jacobs, M. R. 2004. Streptococcus pneumoniae: epidemiology and patterns of resistance. Am. J. Med. 117 (Suppl. 3A):3S15S.
74. Jacobs, M. R.,, D. Felmingham,, P. C. Appelbaum,, and R. N. Gruneberg. 2003. The Alexander Project 1998-2000: susceptibility of pathogens isolated from community-acquired respiratory tract infection to commonly used antimicrobial agents. J. Antimicrob. Chemother. 52:229246.
75. Jones, M. E.,, R. S. Blosser-Middleton,, C. Thornsberry,, J. A. Karlowsky,, and D. F. Sahm. 2003. The activity of levofloxacin and other antimicrobials against clinical isolates of Streptococcus pneumoniae collected worldwide during 1999-2002. Diagn. Microbiol. Infect. Dis. 47:579586.
76. Kampranis, S. C.,, A. D. Bates,, and A. Maxwell. 1999. A model for the mechanism of strand passage by DNA gyrase. Proc. Natl. Acad. Sci. USA 96:84148419.
77. Karlowsky, J. A.,, D. C. Draghi,, C. Thornsberry,, M. E. Jones,, I. A. Critchley,, and D. F. Sahm. 2002. Antimicrobial susceptibilities of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis isolated in two successive respiratory seasons in the US. Int. J. Antimicrob. Agents 20:7685.
78. Klugman, K. P. 2002. The successful clone: the vector of dissemination of resistance in Streptococcus pneumoniae. J. Antimicrob. Chemother. 50 (Suppl. S2):15.
79. Koh, T. H.,, and R. V. Lin. 1997. Increasing antimicrobial resistance in clinical isolates of Streptococcus pneumoniae. Ann. Acad. Med. Singapore 26:604608.
80. Kolesnikov, I. V.,, N. Y. Protasova,, and A. T. Gudkov. 1996. Tetracyclines induce changes in accessibility of ribosomal proteins to proteases. Biochimie 78:868873.
81. Lacks, S. A.,, B. Greenberg,, and P. Lopez. 1995. A cluster of four genes encoding enzymes for five steps in the folate biosynthetic pathway of Streptococcus pneumoniae. J. Bacteriol. 177:6674.
82. Lafitte, D.,, V. Lamour,, P. O. Tsvetkov,, A. A. Makarov,, M. Klich,, P. Deprez,, D. Moras,, C. Briand,, and R. Gilli. 2002. DNA gyrase interaction with coumarin-based inhibitors: the role of the hydroxybenzoate isopentenyl moiety and the 5'- methyl group of the noviose. Biochemistry 41:72177223.
83. Lamour, V.,, L. Hoermann,, J. M. Jeltsch,, P. Oudet,, and D. Moras. 2002. Crystallization of the 43 kDa ATPase domain of Thermus thermophilus gyrase B in complex with novobiocin. Acta Crystallogr. D. Biol. Crystallogr. 58:13761378. Epub, 20 July 2002.
84. Leclercq, R.,, and P. Courvalin. 2002. Resistance to macrolides and related antibiotics in Streptococcus pneumoniae. Antimicrob. Agents Chemother. 46:27272734.
85. Lee, H.,, V. M. Reyes,, and J. Kraut. 1996. Crystal structures of Escherichia coli dihydrofolate reductase complexed with 5- formyltetrahydrofolate (folinic acid) in two space groups: evidence for enolization of pteridine O4. Biochemistry 35:70127020.
86. Lee, H. J.,, J. Y. Park,, S. H. Jang,, J. H. Kim,, E. C. Kim,, and K. W. Choi. 1995. High incidence of resistance to multiple antimicrobials in clinical isolates of Streptococcus pneumoniae from a university hospital in Korea. Clin. Infect. Dis. 20:826835.
87. Lessard, J. L.,, and S. Pestka. 1972. Studies on the formation of transfer ribonucleic acid-ribosome complexes. 23. Chloramphenicol, aminoacyl-oligonucleotides, and Escherichia coli ribosomes. J. Biol. Chem. 247:69096912.
88. Li, R.,, R. Sirawaraporn,, P. Chitnumsub,, W. Sirawaraporn,, J. Wooden,, F. Athappilly,, S. Turley,, and W. G. Hol. 2000. Threedimensional structure of M. tuberculosis dihydrofolate reductase reveals opportunities for the design of novel tuberculosis drugs. J. Mol. Biol. 295:307323.
89. Lim, D.,, and N. C. Strynadka. 2002. Structural basis for the beta lactam resistance of PBP2a from methicillin-resistant Staphylococcus aureus. Nat. Struct. Biol. 9:870876.
90. Lopez, P.,, M. Espinosa,, B. Greenberg,, and S. A. Lacks. 1987. Sulfonamide resistance in Streptococcus pneumoniae: DNA sequence of the gene encoding dihydropteroate synthase and characterization of the enzyme. J. Bacteriol. 169:43204326.
91. Lovett, P. S. 1996. Translation attenuation regulation of chloramphenicol resistance in bacteria—a review. Gene 179:157162.
92. Luna, V. A.,, S. Cousin, Jr.,, W. L. Whittington,, and M. C. Roberts. 2000. Identification of the conjugative mef gene in clinical Acinetobacter junii and Neisseria gonorrhoeae isolates. Antimicrob. Agents Chemother. 44:25032506.
93. 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. 42:613619.
94. Madhi, S. A.,, K. P. Klugman, and The Vaccine Trialist Group. 2004. A role for Streptococcus pneumoniae in virus-associated pneumonia. Nat. Med. 10:811813.
95. Mankin, A. S.,, and R. A. Garrett. 1991. Chloramphenicol resistance mutations in the single 23S rRNA gene of the archaeon Halobacterium halobium. J. Bacteriol. 173:35593563.
96. Maravic, G. 2004. Macrolide resistance based on the Ermmediated rRNA methylation. Curr. Drug Topics—Infect. Disorders 4:193202.
97. Marton, A. 1992. Pneumococcal antimicrobial resistance: the problem in Hungary. Clin. Infect. Dis. 15:106111.
98. Maskell, J. P.,, A. M. Sefton,, and L. M. Hall. 1997. Mechanism of sulfonamide resistance in clinical isolates of Streptococcus pneumoniae. Antimicrob. Agents Chemother. 41:21212126.
99. 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. 45:11041108.
100. 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 Tn917-like sequences within a Tn916-like conjugative transposon (Tn3872) in erythromycin-resistant isolates of Streptococcus pneumoniae. Antimicrob. Agents Chemother. 42:23122318.
101. McGee, L.,, L. McDougal,, J. Zhou,, B. G. Spratt,, F. C. Tenover,, R. George,, R. Hakenbeck,, W. Hryniewicz,, J. C. Lefevre,, A. Tomasz,, and K. P. Klugman. 2001. Nomenclature of major antimicrobial- resistant clones of Streptococcus pneumoniae defined by the pneumococcal molecular epidemiology network. J. Clin. Microbiol. 39:25652571.
102. McMurry, L. M.,, and S. B. Levy,. 2000. Tetracycline resistance in Gram-positive bacteria, p. 660677. In V. Fischetti (ed.), Gram-Positive Pathogens. ASM Press, Washington, D.C.
103. Moazed, D.,, and H. F. Noller. 1987. Chloramphenicol, erythromycin, carbomycin and vernamycin B protect overlapping sites in the peptidyl transferase region of 23S ribosomal RNA. Biochimie 69:879884.
104. Morais Cabral, J. H.,, A. P. Jackson,, C. V. Smith,, N. Shikotra,, A. Maxwell,, and R. C. Liddington. 1997. Crystal structure of the breakage-reunion domain of DNA gyrase. Nature 388: 903906.
105. Morris, J. E.,, X. S. Pan,, and L. M. Fisher. 2002. Grepafloxacin, a dimethyl derivative of ciprofloxacin, acts preferentially through gyrase in Streptococcus pneumoniae: role of the C-5 group in target specificity. Antimicrob. Agents Chemother. 46:582585.
106. Mouz, N.,, E. Gordon,, A. M. Di Guilmi,, I. Petit,, Y. Petillot,, Y. Dupont,, R. Hakenbeck,, T. Vernet,, and O. Dideberg. 1998. Identification of a structural determinant for resistance to beta-lactam antibiotics in gram-positive bacteria. Proc. Natl. Acad. Sci. USA 95:1340313406.
107. Murphy, T. F.,, and S. Sethi. 2002. Chronic obstructive pulmonary disease: role of bacteria and guide to antibacterial selection in the older patient. Drugs Aging 19:761775.
108. Murray, I. A., 2000. Chloramphenicol resistance, p. 678684. In V. Fischetti (ed.), Gram-Positive Pathogens. ASM Press, Washington, D.C.
109. Murray, I. A.,, and W. V. Shaw. 1997. O-Acetyltransferases for chloramphenicol and other natural products. Antimicrob. Agents Chemother. 41:16.
110. Musher, D. M., 2000. Streptococcus pneumoniae, p. 21282147. In G. L. Mandell,, J. E. Bennett,, and R. Dolin (ed.), Principles and Practices of Infectious Disease, 5th ed. Churchill Livingstone, Edinburgh, United Kingdom.
111. Naraqi, S.,, G. P. Kirkpatrick,, and S. Kabins. 1974. Relapsing pneumococcal meningitis: isolation of an organism with decreased susceptibility to penicillin G. J. Pediatr. 85:671673.
112. Ogle, J. M.,, D. E. Brodersen,, W. M. Clemons, Jr.,, M. J. Tarry,, A. P. Carter,, and V. Ramakrishnan. 2001. Recognition of cognate transfer RNA by the 30S ribosomal subunit. Science 292:897902.
113. Ojo, K. K.,, C. Ulep,, N. Van Kirk,, H. Luis,, M. Bernardo,, J. Leitao,, and M. C. Roberts. 2004. The mef(A) gene predominates among seven macrolide resistance genes identified in gram-negative strains representing 13 genera, isolated from healthy Portuguese children. Antimicrob. Agents Chemother. 48:34513456.
114. Oleinick, N. L.,, J. M. Wilhelm,, and J. W. Corcoran. 1968. Nonidentity of the site of action of erythromycin A and chloramphenicol on Bacillus subtilis ribosomes. Biochim. Biophys. Acta 155:290292.
115. Padayachee, T.,, and K. P. Klugman. 1999. Novel expansions of the gene encoding dihydropteroate synthase in trimethoprim- sulfamethoxazole-resistant Streptococcus pneumoniae. Antimicrob. Agents Chemother. 43:22252230.
116. Pan, X. S.,, and L. M. Fisher. 1996. Cloning and characterization of the parC and parE genes of Streptococcus pneumoniae encoding DNA topoisomerase IV: role in fluoroquinolone resistance. J. Bacteriol. 178:40604069.
117. Pan, X. S.,, and L. M. Fisher. 1998. DNA gyrase and topoisomerase IV are dual targets of clinafloxacin action in Streptococcus pneumoniae. Antimicrob. Agents Chemother. 42:28102816.
118. Pan, X. S.,, and L. M. Fisher. 1999. Streptococcus pneumoniae DNA gyrase and topoisomerase IV: overexpression, purification, and differential inhibition by fluoroquinolones. Antimicrob. Agents Chemother. 43:11291136.
119. Pares, S.,, N. Mouz,, Y. Petillot,, R. Hakenbeck,, and O. Dideberg. 1996. X-ray structure of Streptococcus pneumoniae PBP2x, a primary penicillin target enzyme. Nat. Struct. Biol. 3:284289.
120. 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 21:15621571.
121. Perichon, B.,, J. Tankovic,, and P. Courvalin. 1997. Characterization of a mutation in the parE gene that confers fluoroquinolone resistance in Streptococcus pneumoniae. Antimicrob. Agents Chemother. 41:11661167.
122. Pernot, L.,, L. Chesnel,, A. Le Gouellec,, J. Croize,, T. Vernet,, O. Dideberg,, and A. Dessen. 2004. A PBP2x from a clinical isolate of Streptococcus pneumoniae exhibits an alternative mechanism for reduction of susceptibility to beta-lactam antibiotics. J. Biol. Chem. 279:1646316470.
123. 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. 49:553556.
124. Piddock, L. J.,, M. Johnson,, V. Ricci,, and S. L. Hill. 1998. Activities of new fluoroquinolones against fluoroquinoloneresistant pathogens of the lower respiratory tract. Antimicrob. Agents Chemother. 42:29562960.
125. Piddock, L. J.,, M. M. Johnson,, S. Simjee,, and L. Pumbwe. 2002. Expression of efflux pump gene pmrA in fluoroquinolone- resistant and -susceptible clinical isolates of Streptococcus pneumoniae. Antimicrob. Agents Chemother. 46:808812.
126. Pioletti, M.,, F. Schlunzen,, J. Harms,, R. Zarivach,, M. Gluhmann,, H. Avila,, A. Bashan,, H. Bartels,, T. Auerbach,, C. Jacobi,, T. Hartsch,, A. Yonath,, and F. Franceschi. 2001. Crystal structures of complexes of the small ribosomal subunit with tetracycline, edeine and IF3. EMBO J. 20:18291839.
127. Pletz, M. W.,, L. McGee,, J. Jorgensen,, B. Beall,, R. R. Facklam,, C. G. Whitney,, and K. P. Klugman. 2004. Levofloxacinresistant invasive Streptococcus pneumoniae in the United States: evidence for clonal spread and the impact of conjugate pneumococcal vaccine. Antimicrob. Agents Chemother. 48: 34913497.
128. Poehlsgaard, J.,, and S. Douthwaite. 2003. Macrolide antibiotic interaction and resistance on the bacterial ribosome. Curr. Opin. Investig. Drugs 4:140148.
129. Poulsen, S. M.,, C. Kofoed,, and B. Vester. 2000. Inhibition of the ribosomal peptidyl transferase reaction by the mycarose moiety of the antibiotics carbomycin, spiramycin and tylosin. J. Mol. Biol. 304:471481.
130. Pozzi, G.,, F. Iannelli,, M. R. Oggioni,, M. Santagati,, and S. Stefani. 2004. Genetic elements carrying macrolide efflux genes in streptococci. Curr. Drug Topics—Infect. Disorders 4: 203206.
131. Reece, R. J.,, and A. Maxwell. 1991. Probing the limits of the DNA breakage-reunion domain of the Escherichia coli DNA gyrase A protein. J. Biol. Chem. 266:35403546.
132. Reichmann, P.,, A. Konig,, A. Marton,, and R. Hakenbeck. 1996. Penicillin-binding proteins as resistance determinants in clinical isolates of Streptococcus pneumoniae. Microb. Drug Resist. 2:177181.
133. Rheinberger, H. J.,, and K. H. Nierhaus. 1990. Partial release of AcPhe-Phe-tRNA from ribosomes during poly(U)-dependent poly(Phe) synthesis and the effects of chloramphenicol. Eur. J. Biochem. 193:643650.
134. Roberts, M. C. 2004. Distribution of macrolide, lincosamide, streptogramin, ketolide and oxazolidinone (MLSKO) resistance genes in gram-negative bacteria. Curr. Drug Topics—Infect. Disorders 4:207215.
135. 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. 43:28232830.
136. Roca, J.,, J. M. Berger,, S. C. Harrison,, and J. C. Wang. 1996. DNA transport by a type II topoisomerase: direct evidence for a two-gate mechanism. Proc. Natl. Acad. Sci. USA 93:40574062.
137. Rudolph, K. M.,, A. J. Parkinson,, and M. C. Roberts. 2001. Mechanisms of erythromycin and trimethoprim resistance in the Alaskan Streptococcus pneumoniae serotype 6B clone. J. Antimicrob. Chemother. 48:317319.
138. Rybak, M. J. 2004. Increased bacterial resistance: PROTEKT US—an update. Ann. Pharmacother. 38:S8S13.
139. Sangthawan, P.,, S. Chantaratchada,, N. Chanthadisai,, and A. Wattanathum. 2003. Prevalence and clinical significance of community-acquired penicillin-resistant pneumococcal pneumonia in Thailand. Respirology 8:208212.
140. Santagati, M.,, F. Iannelli,, C. Cascone,, F. Campanile,, M. R. Oggioni,, S. Stefani,, and G. Pozzi. 2003. The novel conjugative transposon Tn1207.3 carries the macrolide efflux gene mef(A) in Streptococcus pyogenes. Microb. Drug Resist. 9:243247.
141. 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. 44:25852587.
142. Sauvage, E.,, F. Kerff,, E. Fonze,, R. Herman,, B. Schoot,, J. P. Marquette,, Y. Taburet,, D. Prevost,, J. Dumas,, G. Leonard,, P. Stefanic,, J. Coyette,, and P. Charlier. 2002. The 2.4-Å crystal structure of the penicillin-resistant penicillin-binding protein PBP5fm from Enterococcus faecium in complex with benzylpenicillin. Cell. Mol. Life Sci. 59:12231232.
143. Sawaya, M. R.,, and J. Kraut. 1997. Loop and subdomain movements in the mechanism of Escherichia coli dihydrofolate reductase: crystallographic evidence. Biochemistry 36:586603.
144. Schito, G. C.,, A. Marchese,, D. Elkharrat,, and D. J. Farrell. 2004. Comparative activity of telithromycin against macrolideresistant isolates of Streptococcus pneumoniae: results of two years of the PROTEKT surveillance study. J. Chemother. 16:1322.
145. Schlunzen, F.,, J. M. Harms,, F. Franceschi,, H. A. Hansen,, H. Bartels,, R. Zarivach,, and A. Yonath. 2003. Structural basis for the antibiotic activity of ketolides and azalides. Structure (Camb.) 11:329338.
146. 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 413:814821.
147. Schmitz, F. J.,, M. Perdikouli,, A. Beeck,, J. Verhoef,, and A. C. Fluit. 2001. Resistance to trimethoprim-sulfamethoxazole and modifications in genes coding for dihydrofolate reductase and dihydropteroate synthase in European Streptococcus pneumoniae isolates. J. Antimicrob. Chemother. 48:935936.
148. Schneider, P.,, S. Hawser,, and K. Islam. 2003. Iclaprim, a novel diaminopyrimidine with potent activity on trimethoprim sensitive and resistant bacteria. Bioorg. Med. Chem. Lett. 13:42174221.
149. Schrag, S. J.,, L. McGee,, C. G. Whitney,, B. Beall,, A. S. Craig,, M. E. Choate,, J. H. Jorgensen,, R. R. Facklam,, and K. P. Klugman. 2004. Emergence of Streptococcus pneumoniae with very-high-level resistance to penicillin. Antimicrob. Agents Chemother. 48:30163023.
150. Seral, C.,, F. J. Castillo,, C. Garcia,, M. C. Rubio-Calvo,, and R. Gomez-Lus. 2000. Presence of conjugative transposon Tn1545 in strains of Streptococcus pneumoniae with mef(A), erm(B), tet(M), catpC194 and aph3'-III genes. Enferm. Infecc. Microbiol. Clin. 18:506511.
151. Seral, C.,, F. J. Castillo,, M. C. Rubio-Calvo,, A. Fenoll,, C. Garcia,, and R. Gomez-Lus. 2001. Distribution of resistance genes tet(M), aph3'-III, catpC194 and the integrase gene of Tn1545 in clinical Streptococcus pneumoniae harbouring erm(B) and mef(A) genes in Spain. J. Antimicrob. Chemother. 47:863866.
152. Setchanova, L.,, and A. Tomasz. 1999. Molecular characterization of penicillin-resistant Streptococcus pneumoniae isolates from Bulgaria. J. Clin. Microbiol. 37:638648.
153. Shaw, K.,, and G. D. Wright,. 2000. Aminoglycoside resistance in gram-positive bacteria, p. 635646. In V. Fischetti (ed.), Gram-Positive Pathogens. ASM Press, Washington, D.C.
154. Shortridge, V. D.,, R. K. Flamm,, N. Ramer,, J. Beyer,, and S. K. Tanaka. 1996. Novel mechanism of macrolide resistance in Streptococcus pneumoniae. Diagn. Microbiol. Infect. Dis. 26:7378.
155. Sibold, C.,, J. Henrichsen,, A. Konig,, C. Martin,, L. Chalkley,, and R. Hakenbeck. 1994. Mosaic pbpX genes of major clones of penicillin-resistant Streptococcus pneumoniae have evolved from pbpX genes of a penicillin-sensitive Streptococcus oralis. Mol. Microbiol. 12:10131023.
156. Sibold, C.,, J. Wang,, J. Henrichsen,, and R. Hakenbeck. 1992. Genetic relationships of penicillin-susceptible and -resistant Streptococcus pneumoniae strains isolated on different continents. Infect. Immun. 60:41194126.
157. Stadler, C.,, and M. Teuber. 2002. The macrolide efflux genetic assembly of Streptococcus pneumoniae is present in erythromycin- resistant Streptococcus salivarius. Antimicrob. Agents Chemother. 46:36903691.
158. Sutcliffe, J. 2001. MLSBK Resistance Update, Presented at the 5th International Antibacterial Drug Discovery and Development Summit, Princeton, N.J.
159. Sutcliffe, J.,, and R. Leclercq,. 2002. Mechanisms of resistance to macrolides, lincosamides, and ketolides, p. 281317. In W. Schonfeld, and H. A. Kirst (ed.), Macrolide Antibiotics. Birkhauser Verlag, Basel, Germany.
160. 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. 40:18171824.
161. Syrogiannopoulos, G. A.,, I. N. Grivea,, L. M. Ednie,, B. Bozdogan,, G. D. Katopodis,, N. G. Beratis,, T. A. Davies,, and P. C. Appelbaum. 2003. Antimicrobial susceptibility and macrolide resistance inducibility of Streptococcus pneumoniae carrying erm(A), erm(B), or mef(A). Antimicrob. Agents Chemother. 47:26992702.
162. Syrogiannopoulos, G. A.,, I. N. Grivea,, A. Tait-Kamradt,, G. D. Katopodis,, N. G. Beratis,, J. Sutcliffe,, P. C. Appelbaum,, and T. D. Davies. 2000. Identification of erm(A) erythromycin resistance methylase gene in Streptococcus pneumoniae isolated in Greece. Antimicrob. Agents Chemother. 45:342344.
163. 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. 41:22512255.
164. 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. 44:33953401.
165. Takenouchi, T.,, F. Tabata,, Y. Iwata,, H. Hanzawa,, M. Sugawara,, and S. Ohya. 1996. Hydrophilicity of quinolones is not an exclusive factor for decreased activity in efflux-mediated resistant mutants of Staphylococcus aureus. Antimicrob. Agents Chemother. 40:18351842.
166. Tenson, T.,, and M. Ehrenberg. 2002. Regulatory nascent peptides in the ribosomal tunnel. Cell 108:591594.
167. Tenson, T.,, M. Lovmar,, and M. Ehrenberg. 2003. The mechanism of action of macrolides, lincosamides and streptogramin B reveals the nascent peptide exit path in the ribosome. J. Mol. Biol. 330:10051014.
168. Thompson, J.,, M. O’Connor,, J. A. Mills,, and A. E. Dahlberg. 2002. The protein synthesis inhibitors, oxazolidinones and chloramphenicol, cause extensive translational inaccuracy in vivo. J. Mol. Biol. 322:273279.
169. Thornsberry, C.,, D. F. Sahm,, L. J. Kelly,, I. A. Critchley,, M. E. Jones,, A. T. Evangelista,, and J. A. Karlowsky. 2002. Regional trends in antimicrobial resistance among clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in the United States: results from the TRUST Surveillance Program, 1999-2000. Clin. Infect. Dis. 34 (Suppl. 1):S4S16.
170. Tomasz, A.,, and W. Fischer,. 2000. The cell wall of Streptococcus pneumoniae, p. 191-200. In V. Fischetti (ed.), Gram- Positive Pathogens. ASM Press, Washington, D.C.
171. Trieu-Cuot, P.,, and P. Courvalin. 1983. Nucleotide sequence of the Streptococcus faecalis plasmid gene encoding the 3′5″- aminoglycoside phosphotransferase type III. Gene 23:331341.
172. Trieu-Cuot, P.,, C. Poyart-Salmeron,, C. Carlier,, and P. Courvalin. 1990. Nucleotide sequence of the erythromycin resistance gene of the conjugative transposon Tn1545. Nucleic Acids Res. 18:3660.
173. Tsai, F. T.,, O. M. Singh,, T. Skarzynski,, A. J. Wonacott,, S. Weston,, A. Tucker,, R. A. Pauptit,, A. L. Breeze,, J. P. Poyser,, R. O’Brien,, J. E. Ladbury,, and D. B. Wigley. 1997. The highresolution crystal structure of a 24-kDa gyrase B fragment from E. coli complexed with one of the most potent coumarin inhibitors, clorobiocin. Proteins 28:4152.
174. Vester, B.,, and S. Douthwaite. 2001. Macrolide resistance conferred by base substitutions in 23S rRNA. Antimicrob. Agents Chemother. 45:112.
175. Vester, B.,, and R. A. Garrett. 1988. The importance of highly conserved nucleotides in the binding region of chloramphenicol at the peptidyl transfer centre of Escherichia coli 23S ribosomal RNA. EMBO J. 7:35773587.
176. Weigel, L. M.,, G. J. Anderson,, R. R. Facklam,, and F. C. Tenover. 2001. Genetic analyses of mutations contributing to fluoroquinolone resistance in clinical isolates of Streptococcus pneumoniae. Antimicrob. Agents Chemother. 45:35173523.
177. 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. 348:17371746.
178. 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. 343:19171924.
179. 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. 44:393395.
180. Widdowson, C. A.,, and K. P. Klugman. 1999. Molecular mechanisms of resistance to commonly used non-betalactam drugs in Streptococcus pneumoniae. Semin. Respir. Infect. 14:255268.
181. Widdowson, C. A.,, K. P. Klugman,, and D. Hanslo. 1996. Identification of the tetracycline resistance gene, tet(O), in Streptococcus pneumoniae. Antimicrob. Agents Chemother. 40:28912893.
182. Wigley, D. B.,, G. J. Davies,, E. J. Dodson,, A. Maxwell,, and G. Dodson. 1991. Crystal structure of an N-terminal fragment of the DNA gyrase B protein. Nature 351:624629.
183. Willmott, C. J.,, and A. Maxwell. 1993. A single point mutation in the DNA gyrase A protein greatly reduces binding of fluoroquinolones to the gyrase-DNA complex. Antimicrob. Agents Chemother. 37:126127.
184. Yother, J. 2000. Genetics of Streptococcus pneumoniae, p. 232-243. In V. Fischetti (ed.), Gram-Positive Pathogens. ASM Press, Washington, D.C

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