Molecular basis and phenotype of methicillin resistance in Staphylococcus aureus and insights into new β-lactams that meet the challenge

Antimicrobial Agents and Chemotherapy

Volumn 53, Issue 10, 2009, Pages 4051-4063

  Llarrull, Leticia I ^a   Fisher, Jed F ^a   Mobashery, Shahriar ^a  

^a UNIVERSITY OF NOTRE DAME   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AZTREONAM; BACTERIAL PROTEIN; BETA LACTAM ANTIBIOTIC; CEFTAROLINE; CEFTAROLINE FOSAMIL; CEFTAZIDIME; CEFTOBIPROLE; CEFTOBIPROLE MEDOCARIL; CILASTIN; DALBAVANCIN; DALFOPRISTIN PLUS QUINUPRISTIN; DAPTOMYCIN; LINEZOLID; ME 1036; ORITAVANCIN; OXAZOLIDINONE DERIVATIVE; PENICILLIN BINDING PROTEIN; PENICILLIN BINDING PROTEIN 2A; PEPTIDOGLYCAN; PROTEIN INHIBITOR; PTK 0796; PZ 601; RAZUPENEM; RX 1741; STREPTOGRAMIN; TEICOPLANIN; TETRACYCLINE DERIVATIVE; TIGECYCLINE; TR 701; UNCLASSIFIED DRUG; UNINDEXED DRUG; VANCOMYCIN;

ABSENCE OF SIDE EFFECTS; ANTIBIOTIC RESISTANCE; BACTERIAL CELL WALL; BACTERIAL ENDOCARDITIS; BACTERIAL GENE; BACTERIAL GENETICS; BACTERIAL VIRULENCE; BACTERICIDAL ACTIVITY; BACTERIUM ISOLATE; BIOSYNTHESIS; COMMUNITY; COMMUNITY ACQUIRED PNEUMONIA; COMPLICATED SKIN AND SKIN STRUCTURE INFECTION; EVOLUTION; GENE SEQUENCE; GRAM NEGATIVE INFECTION; HUMAN; IC 50; MEMBRANE STRUCTURE; METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS; METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS INFECTION; MINIMUM INHIBITORY CONCENTRATION; MONOTHERAPY; MULTIDRUG RESISTANCE; NONHUMAN; PENICILLIN RESISTANCE; PHENOTYPE; PRIORITY JOURNAL; SHORT SURVEY; SKIN INFECTION; STAPHYLOCOCCUS INFECTION; STAPHYLOCOCCUS SCIURI; STREPTOCOCCUS PNEUMONIAE;

ANTI-BACTERIAL AGENTS; BETA-LACTAMS; CELL WALL; METHICILLIN RESISTANCE; METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS; PENICILLIN-BINDING PROTEINS; PEPTIDE SYNTHASES; STAPHYLOCOCCUS AUREUS;

EID: 70349326664     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.00084-09     Document Type: Short Survey

References (189)

1. Abbanat, D., B. Morrow, and K. Bush. 2008. New agents in development for the treatment of bacterial infections. Curr. Opin. Pharmacol. 8:582-592.
2. Aksoy, D. Y., and S. Unal. 2008. New antimicrobial agents for the treatment of gram-positive bacterial infections. Clin. Microbiol. Infect. 14:411-420.
3. Anderson, S. D., and J. G. Gums. 2008. Ceftobiprole: an extended-spectrum anti-methicillin-resistant Staphylococcus aureus cephalosporin. Ann. Pharmacother. 42:806-816.
4. Andes, D., and W. Craig. 2008. In vivo pharmacodynamic activity of carbapenem ME1036 in a murine thigh infection model, poster A-032. Abstr. 48th Annu. Intersci. Conf. Antimicrob. Agents. Chemother. (ICAAC)/Infect. Dis. Soc. Am. (IDSA) 46th Annu. Meet. American Society for Microbiology and Infectious Diseases Society of America, Washington, DC.
5. Antignac, A., and A. Tomasz. 2009. Reconstruction of the phenotypes of methicillin-resistant Staphylococcus aureus by replacement of the staphylococcal cassette chromosome mec with a plasmid-borne copy of Staphylococcus sciuri pbpD gene. Antimicrob. Agents Chemother. 53:435-441.
6. Appelbaum, P. C. 2007. Microbiology of antibiotic resistance in Staphylococcus aureus. Clin. Infect. Dis. 45(Suppl. 3):S165-S170.
7. Arias, C. A., and B. E. Murray. 2009. Antibiotic-resistant bugs in the 21st century-a clinical super-challenge. N. Engl. J. Med. 360:439-443.
8. Banerjee, R., M. Gretes, L. Basuino, N. Strynadka, and H. F. Chambers. 2008. In vitro selection and characterization of ceftobiprole-resistant methicillin-resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 52: 2089-2096.
9. Belcheva, A., and D. Golemi-Kotra. 2008. A close-up view of the VraSR two-component system. A mediator of Staphylococcus aureus response to cell wall damage. J. Biol. Chem. 283:12354-12364.
10. Ben Zakour, N. L., C. M. Guinane, and J. R. Fitzgerald. 2008. Pathogenomics of the staphylococci: insights into niche adaptation and the emergence of new virulent strains. FEMS Microbiol. Lett. 289:1-12.
11. Berger-Bachi, B. 1999. Genetic basis of methicillin resistance in Staphylococcus aureus. Cell. Mol. Life Sci. 56:764-770.
12. Berger-Bachi, B., and S. Rohrer. 2002. Factors influencing methicillin resistance in staphylococci. Arch. Microbiol. 178:165-171.
13. Berger-Bachi, B., A. Strassle, J. E. Gustafson, and F. H. Kayser. 1992. Mapping and characterization of multiple chromosomal factors involved in methicillin resistance in Staphylococcus aureus. Antimicrob. Agents Chemother. 36:1367-1373.
14. Berger-Bachi, B., and M. Tschierske. 1998. Role of fem factors in methicillin resistance. Drug Resist. Updat. 1:325-335.
15. Bogdanovich, T., L. M. Ednie, S. Shapiro, and P. C. Appelbaum. 2005. Antistaphylococcal activity of ceftobiprole, a new broad-spectrum cephalosporin. Antimicrob. Agents Chemother. 49:4210-4219.
16. Boucher, H. W., and G. R. Corey. 2008. Epidemiology of methicillin-resistant Staphylococcus aureus. Clin. Infect. Dis. 46(Suppl. 5):S344-S349.
17. Boucher, H. W., G. H. Talbot, J. S. Bradley, J. E. Edwards, D. Gilbert, L. B. Rice, M. Scheld, B. Spellberg, and J. Bartlett. 2009. Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin. Infect. Dis. 48:1-12.
18. Boyle-Vavra, S., S. Yin, and R. S. Daum. 2006. The VraS/VraR two-component regulatory system required for oxacillin resistance in communityacquired methicillin-resistant Staphylococcus aureus. FEMS Microbiol. Lett. 262:163-171. (Pubitemid 44272791)
19. Braaten, D. 2007. Bugs vs drugs. Nat. Med. 13:522-523.
20. Bush, K., M. Heep, M. J. Macielag, and G. J. Noel. 2007. Anti-MRSA beta-lactams in development, with a focus on ceftobiprole: the first anti-MRSA beta-lactam to demonstrate clinical efficacy. Expert Opin. Investig. Drugs 16:419-429.
21. Butler, M. S. 2008. Natural products to drugs: natural product-derived compounds in clinical trials. Nat. Prod. Rep. 25:475-516.
22. Butler, M. S., and A. D. Buss. 2006. Natural products-the future scaffolds for novel antibiotics? Biochem. Pharmacol. 71:919-929.
23. Cha, J., S. B. Vakulenko, and S. Mobashery. 2007. Characterization of the β-lactam antibiotic sensor domain of the MecR1 signal sensor/transducer protein from methicillin-resistant Staphylococcus aureus. Biochemistry 46: 7822-7831. (Pubitemid 47016065)
24. Chambers, H. F. 2001. The changing epidemiology of Staphylococcus aureus? Emerg. Infect. Dis. 7:178-182.
25. Chambers, H. F. 1997. Methicillin resistance in staphylococci: molecular and biochemical basis and clinical implications. Clin. Microbiol. Rev. 10: 781-791.
26. Chambers, H. F. 2005. Community-associated MRSA-resistance and virulence converge. N. Engl. J. Med. 352:1485-1487.
27. Chambers, H. F. 2009. Pathogenesis of staphylococcal infection: a manner of expression. J. Infect. Dis. 199:291-293.
28. Chambers, H. F., and S. S. Hegde. 2007. Combating the growing problem of methicillin-resistant Staphylococcus aureus: do the newer antibiotics represent a better alternative to vancomycin? Expert. Rev. Anti-Infect. Ther. 5:333-335.
29. Cheng, T. J., M. T. Sung, H. Y. Liao, Y. F. Chang, C. W. Chen, C. Y. Huang, L. Y. Chou, Y. D. Wu, Y. H. Chen, Y. S. Cheng, C. H. Wong, C. Ma, and W. C. Cheng. 2008. Domain requirement of moenomycin binding to bifunctional transglycosylases and development of high-throughput discovery of antibiotics. Proc. Natl. Acad. Sci. USA 105:431-436.
30. Cho, S., Q. Wang, C. P. Swaminathan, D. Hesek, M. Lee, G. J. Boons, S. Mobashery, and R. A. Mariuzza. 2007. Structural insights into the bactericidal mechanism of human peptidoglycan recognition proteins. Proc. Natl. Acad. Sci. USA 104:8761-8766.
31. Chongtrakool, P., T. Ito, X. X. Ma, Y. Kondo, S. Trakulsomboon, C. Tiensasitorn, M. Jamklang, T. Chavalit, J. H. Song, and K. Hiramatsu. 2006. Staphylococcal cassette chromosome mec (SCCmec) typing of methicillinresistant Staphylococcus aureus strains isolated in 11 Asian countries: a proposal for a new nomenclature for SCCmec elements. Antimicrob. Agents Chemother. 50:1001-1012.
32. Chung, M., A. Antignac, C. Kim, and A. Tomasz. 2008. Comparative study of the susceptibilities of major epidemic clones of methicillin-resistant Staphylococcus aureus to oxacillin and to the new broad-spectrum cephalosporin ceftobiprole. Antimicrob. Agents Chemother. 52:2709-2717.
33. Clardy, J., M. A. Fischbach, and C. T. Walsh. 2006. New antibiotics from bacterial natural products. Nat. Biotechnol. 24:1541-1550.
34. Clark, C., K. Kosowska-Shick, P. McGhee, and P. C. Appelbaum. 2008. Capability of PZ-601 (SMP-601) to select for resistant mutants of vancomycin-susceptible and non-susceptible MRSA, poster C1-195. Abstr. 48th Annu. Intersci. Conf. Antimicrob. Agents. Chemother. (ICAAC)/Infect. Dis. Soc. Am. (IDSA) 46th Annu. Meet. American Society for Microbiology and Infectious Diseases Society of America, Washington, DC.
35. Clarke, S. R., and K. G. Dyke. 2001. Studies of the operator region of the Staphylococcus aureus beta-lactamase operon. J. Antimicrob. Chemother. 47:377-389.
36. Corey, G. R., M. Wilcox, G. H. Talbot, T. Baculik, and D. Thye. 2008. CANVAS-1: randomized, double-blinded, phase 3 study (P903-06) of the efficacy and safety of ceftaroline vs. vancomycin plus aztreonam in complicated skin and skin structure infections (cSSSI), poster L-1515a. Abstr. 48th Annu. Intersci. Conf. Antimicrob. Agents. Chemother. (ICAAC)/Infect. Dis. Soc. Am. (IDSA) 46th Annu. Meet. American Society for Microbiology and Infectious Diseases Society of America, Washington, DC.
37. Couto, I., H. de Lencastre, E. Severina, W. Kloos, J. A. Webster, R. J. Hubner, I. S. Sanches, and A. Tomasz. 1996. Ubiquitous presence of a mecA homologue in natural isolates of Staphylococcus sciuri. Microb. Drug Resist. 2:377-391.
38. Couto, I., I. S. Sanches, R. Sa-Leao, and H. de Lencastre. 2000. Molecular characterization of Staphylococcus sciuri strains isolated from humans. J. Clin. Microbiol. 38:1136-1143.
39. Couto, I., S. W. Wu, A. Tomasz, and H. de Lencastre. 2003. Development of methicillin resistance in clinical isolates of Staphylococcus sciuri by transcriptional activation of the mecA homologue native to the species. J. Bacteriol. 185:645-653.
40. Crisostomo, M. I., H. Westh, A. Tomasz, M. Chung, D. C. Oliveira, and H. de Lencastre. 2001. The evolution of methicillin resistance in Staphylococcus aureus: similarity of genetic backgrounds in historically early methicillin-susceptible and -resistant isolates and contemporary epidemic clones. Proc. Natl. Acad. Sci. USA 98:9865-9870.
41. D'Agata, E. M., G. F. Webb, M. A. Horn, R. C. J. Moellering, and S. Ruan. 2009. Modeling the invasion of community-acquired methicillin-resistant Staphylococcus aureus into hospitals. Clin. Infect. Dis. 48:274-284.
42. David, M. Z., D. Glikman, S. E. Crawford, J. Peng, K. J. King, M. A. Hostetler, S. Boyle-Vavra, and R. S. Daum. 2008. What is communityassociated methicillin-resistant Staphylococcus aureus? J. Infect. Dis. 197: 1235-1243.
43. Davies, T. A., M. G. Page, W. Shang, T. Andrew, M. Kania, and K. Bush. 2007. Binding of ceftobiprole and comparators to the penicillin-binding proteins of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pneumoniae. Antimicrob. Agents Chemother. 51: 2621-2624.
44. de Lencastre, H., B. L. de Jonge, P. R. Matthews, and A. Tomasz. 1994. Molecular aspects of methicillin resistance in Staphylococcus aureus. J. Antimicrob. Chemother. 33:7-24.
45. de Lencastre, H., D. Oliveira, and A. Tomasz. 2007. Antibiotic resistant Staphylococcus aureus: a paradigm of adaptive power. Curr. Opin. Microbiol. 10:428-435.
46. de Lencastre, H., and A. Tomasz. 1994. Reassessment of the number of auxiliary genes essential for expression of high-level methicillin resistance in Staphylococcus aureus. Antimicrob. Agents Chemother. 38:2590-2598.
47. de Lencastre, H., and A. Tomasz. 2007. Multiple stages in the evolution of the methicillin resistant Staphylococcus aureus, p. 333-346. In F. Baquero, C. Nombela, G. H. Cassell, and J. A. Gutierrez-Fuentes (ed.), Evolutionary biology of bacterial and fungal pathogens. ASM Press, Washington, DC.
48. Deurenberg, R. H., and E. E. Stobberingh. 2008. The evolution of Staphylococcus aureus. Infect. Genet. Evol. 8:747-763.
49. Diep, B. A., S. R. Gill, R. F. Chang, T. H. Phan, J. H. Chen, M. G. Davidson, F. Lin, J. Lin, H. A. Carleton, E. F. Mongodin, G. F. Sensabaugh, and F. Perdreau-Remington. 2006. Complete genome sequence of USA300, an epidemic clone of community-acquired methicillin-resistant Staphylococcus aureus. Lancet 367:731-739.
50. Diep, B. A., and M. Otto. 2008. The role of virulence determinants in community-associated MRSA pathogenesis. Trends Microbiol. 16:361-369.
51. Diep, B. A., A. M. Palazzolo-Ballance, P. Tattevin, L. Basuino, K. R. Braughton, A. R. Whitney, L. Chen, B. N. Kreiswirth, M. Otto, F. R. DeLeo, and H. F. Chambers. 2008. Contribution of Panton-Valentine leukocidin in community-associated methicillin-resistant Staphylococcus aureus pathogenesis. PLoS One 3:e3198.
52. Enright, M. C., D. A. Robinson, G. Randle, E. J. Feil, H. Grundmann, and B. G. Spratt. 2002. The evolutionary history of methicillin-resistant Staphylococcus aureus (MRSA). Proc. Natl. Acad. Sci. USA 99:7687-7692.
53. Escaich, S. 2008. Antivirulence as a new antibacterial approach for chemotherapy. Curr. Opin. Chem. Biol. 12:400-408.
54. Fan, X., Y. Liu, D. Smith, L. Konermann, K. W. Siu, and D. Golemi-Kotra. 2007. Diversity of penicillin-binding proteins. Resistance factor FmtA of Staphylococcus aureus. J. Biol. Chem. 282:35143-35152.
55. Forbes, B. A., K. Bombicino, K. Plata, A. Cuirolo, D. Webber, C. L. Bender, and A. E. Rosato. 2008. Unusual form of oxacillin resistance in methicillinresistant Staphylococcus aureus clinical strains. Diagn. Microbiol. Infect. Dis. 61:387-395.
56. Fuda, C., D. Hesek, M. Lee, K. Morio, T. Nowak, and S. Mobashery. 2005. Activation for catalysis of penicillin-binding protein 2a from methicillinresistant Staphylococcus aureus by bacterial cell wall. J. Am. Chem. Soc. 127:2056-2057.
57. Fuda, C., M. Suvorov, Q. Shi, D. Hesek, M. Lee, and S. Mobashery. 2007. Shared functional attributes between the mecA gene product of Staphylococcus sciuri and penicillin-binding protein 2a of methicillin-resistant Staphylococcus aureus. Biochemistry 46:8050-8057. (Pubitemid 47051640)
58. Fuda, C., M. Suvorov, S. B. Vakulenko, and S. Mobashery. 2004. The basis for resistance to beta-lactam antibiotics by penicillin-binding protein 2a of methicillin-resistant Staphylococcus aureus. J. Biol. Chem. 279:40802-40806.
59. Fuda, C. C. S., J. F. Fisher, and S. Mobashery. 2005. Beta-lactam resistance in Staphylococcus aureus: the adaptive resistance of a plastic genome. Cell. Mol. Life Sci. 62:2617-2633.
60. Fujimoto, K., T. Uda, and K. Kanazawa. 2008. In vitro and in vivo efficacy of SMP-601 (SMP; PZ-601), a novel anti-MRSA carbapenem, against clinical isolates of MRSA in Japan, poster F1-360. Abstr. 48th Annu. Intersci. Conf. Antimicrob. Agents. Chemother. (ICAAC)/Infect. Dis. Soc. Am. (IDSA) 46th Annu. Meet. American Society for Microbiology and Infectious Diseases Society of America, Washington, DC.
61. Gardete, S., S. W. Wu, S. Gill, and A. Tomasz. 2006. Role of VraSR in antibiotic resistance and antibiotic-induced stress response in Staphylococcus aureus. Antimicrob. Agents Chemother. 50:3424-3434.
62. Ge, Y., R. Redman, L. Floren, S. Liao, and M. Wikler. 2006. The pharmacokinetics (PK) and safety of ceftaroline (PPI-0903) in healthy subjects receiving multiple-dose intravenous (IV) infusions, poster A-1937. Abstr. 46th Intersci. Conf. Antimicrob. Agents Chemother. American Society for Microbiology, Washington, DC.
63. Ge, Y., D. Thye, S. Liao, and G. H. Talbot. 2006. Pharmacokinetics (PK) of ceftaroline (PPI0903) in subjects with mild or moderate renal impairment (RI), poster A-1939. Abstr. 46th Intersci. Conf. Antimicrob. Agents Chemother. American Society for Microbiology, Washington, DC.
64. Ge, Y., S. Liao, and G. H. Talbot. 2007. Population pharmacokinetics (PK) analysis of ceftaroline (CPT) in volunteers and patients with complicated skin and skin structure infection (cSSSI), poster A-34. Abstr. 47th Intersci. Conf. Antimicrob. Agents Chemother. American Society for Microbiology, Washington, DC.
65. Geronimus, L. H., and S. Cohen. 1957. Induction of staphylococcal penicillinase. J. Bacteriol. 73:28-34.
66. Ghosh, A. S., C. Chowdhury, and D. E. Nelson. 2008. Physiological functions of D-alanine carboxypeptidases in Escherichia coli. Trends Microbiol. 16:309-317.
67. Gill, S. R., D. E. Fouts, G. L. Archer, E. F. Mongodin, R. T. Deboy, J. Ravel, I. T. Paulsen, J. F. Kolonay, L. Brinkac, M. Beanan, R. J. Dodson, S. C. Daugherty, R. Madupu, S. V. Angiuoli, A. S. Durkin, D. H. Haft, J. Vamathevan, H. Khouri, T. Utterback, C. Lee, G. Dimitrov, L. Jiang, H. Qin, J. Weidman, K. Tran, K. Kang, I. R. Hance, K. E. Nelson, and C. M. Fraser. 2005. Insights on evolution of virulence and resistance from the complete genome analysis of an early methicillin-resistant Staphylococcus aureus strain and a biofilm-producing methicillin-resistant Staphylococcus epidermidis strain. J. Bacteriol. 187:2426-2438.
68. Goffin, C., and J. M. Ghuysen. 2002. Biochemistry and comparative genomics of SxxK superfamily acyltransferases offer a clue to the mycobacterial paradox: presence of penicillin-susceptible target proteins versus lack of efficiency of penicillin as therapeutic agent. Microbiol. Mol. Biol. Rev. 66:702-738.
69. Golemi-Kotra, D., J. Y. Cha, S. O. Meroueh, S. B. Vakulenko, and S. Mobashery. 2003. Resistance to β-lactam antibiotics and its mediation by the sensor domain of the transmembrane BlaR signaling pathway in Staphylococcus aureus. J. Biol. Chem. 278:18419-18425. (Pubitemid 36799464)
70. Grundmann, H., M. Aires-de-Sousa, J. Boyce, and E. Tiemersma. 2006. Emergence and resurgence of methicillin-resistant Staphylococcus aureus as a public-health threat. Lancet 368:874-885.
71. Guan, R., and R. A. Mariuzza. 2007. Peptidoglycan recognition proteins of the innate immune system. Trends Microbiol. 15:127-134. (Pubitemid 46356982)
72. Guan, R., A. Roychowdhury, B. Ember, S. Kumar, G. J. Boons, and R. A. Mariuzza. 2004. Structural basis for peptidoglycan binding by peptidoglycan recognition proteins. Proc. Natl. Acad. Sci. USA 101:17168-17173.
73. Guignard, B., J. M. Entenza, and P. Moreillon. 2005. Beta-lactams against methicillin-resistant Staphylococcus aureus. Curr. Opin. Pharmacol. 5:479-489.
74. Hancock, R. E. 2005. Mechanisms of action of newer antibiotics for grampositive pathogens. Lancet Infect. Dis. 5:209-218.
75. Haydon, D. J., N. R. Stokes, R. Ure, G. Galbraith, J. M. Bennett, D. R. Brown, P. J. Baker, V. V. Barynin, D. W. Rice, S. E. Sedelnikova, J. R. Heal, J. M. Sheridan, S. T. Aiwale, P. K. Chauhan, A. Srivastava, A. Taneja, I. Collins, J. Errington, and L. G. Czaplewski. 2008. An inhibitor of FtsZ with potent and selective anti-staphylococcal activity. Science 321:1673-1675.
76. Heller, S., E. Marrer, M. G. P. Page, S. Shapiro, and L. Thenoz. 2004. Development of endogenous resistance by staphylococci to BAL9141 and comparators, abstr. P675. Clin. Microbiol. Infect. 10:163.
77. Hinshaw, R. R., R. D. Schaadt, B. Murray, D. Stapert, D. Biek, Y. Ge, G. E. Zurenko, and D. Shinabarger. 2008. Spontaneous mutation frequency and serial passage resistance development studies with ceftaroline (CPT), poster C1-185. Abstr. 48th Annu. Intersci. Conf. Antimicrob. Agents. Chemother. (ICAAC)/Infect. Dis. Soc. Am. (IDSA) 46th Annu. Meet. American Society for Microbiology and Infectious Diseases Society of America, Washington, DC.
78. Hiramatsu, K. 1995. Molecular evolution of MRSA. Microbiol. Immunol. 39:531-543.
79. Hiramatsu, K., K. Asada, E. Suzuki, K. Okonogi, and T. Yokota. 1992. Molecular cloning and nucleotide sequence determination of the regulator region of mecA gene in methicillin-resistant Staphylococcus aureus (MRSA). FEBS Lett. 298:133-136.
80. Hiramatsu, K., L. Cui, M. Kuroda, and T. Ito. 2001. The emergence and evolution of methicillin-resistant Staphylococcus aureus. Trends Microbiol. 9:486-493.
81. Holden, M. T., E. J. Feil, J. A. Lindsay, S. J. Peacock, N. P. Day, M. C. Enright, T. J. Foster, C. E. Moore, L. Hurst, R. Atkin, A. Barron, N. Bason, S. D. Bentley, C. Chillingworth, T. Chillingworth, C. Churcher, L. Clark, C. Corton, A. Cronin, J. Doggett, L. Dowd, T. Feltwell, Z. Hance, B. Harris, H. Hauser, S. Holroyd, K. Jagels, K. D. James, N. Lennard, A. Line, R. Mayes, S. Moule, K. Mungall, D. Ormond, M. A. Quail, E. Rabbinowitsch, K. Rutherford, M. Sanders, S. Sharp, M. Simmonds, K. Stevens, S. Whitehead, B. G. Barrell, B. G. Spratt, and J. Parkhill. 2004. Complete genomes of two clinical Staphylococcus aureus strains: evidence for the rapid evolution of virulence and drug resistance. Proc. Natl. Acad. Sci. USA 101:9786-9791.
82. Hososaka, Y., H. Hanaki, H. Endo, Y. Suzuki, Z. Nagasawa, Y. Otsuka, T. Nakae, and K. Sunakawa. 2007. Characterization of oxacillin-susceptible mecA-positive Staphylococcus aureus: a new type of MRSA. J. Infect. Chemother. 13:79-86.
83. Ikonomidis, A., G. Michail, A. Vasdeki, M. Labrou, V. Karavasilis, C. Stathopoulos, A. N. Maniatis, and S. Pournaras. 2008. In vitro and in vivo evaluations of oxacillin efficiency against mecA-positive oxacillin-susceptible Staphylococcus aureus. Antimicrob. Agents Chemother. 52:3905-3908.
84. Jacqueline, C., J. Caillon, V. Le Mabecque, A. F. Miegeville, A. Hamel, D. Bugnon, J. Y. Ge, and G. Potel. 2007. In vivo efficacy of ceftaroline (PPI-0903), a new broad-spectrum cephalosporin, compared with linezolid and vancomycin against methicillin-resistant and vancomycin-intermediate Staphylococcus aureus in a rabbit endocarditis model. Antimicrob. Agents Chemother. 51:3397-3400.
85. Jones, R. N. 2003. Global epidemiology of antimicrobial resistance among community-acquired and nosocomial pathogens: a five-year summary from the SENTRY Antimicrobial Surveillance Program (1997-2001). Semin. Respir. Crit. Care. Med. 24:121-134.
86. Kampf, G., S. Adena, H. Ruden, and K. Weist. 2003. Inducibility and potential role of mecA-gene-positive oxacillin-susceptible Staphylococcus aureus from colonized healthcare workers as a source for nosocomial infections. J. Hosp. Infect. 54:124-129.
87. Katayama, Y., T. Ito, and K. Hiramatsu. 2000. A new class of genetic element, staphylococcus cassette chromosome mec, encodes methicillin resistance in Staphylococcus aureus. Antimicrob. Agents Chemother. 44:1549-1555. (Pubitemid 30340793)
88. Katayama, Y., T. Ito, and K. Hiramatsu. 2001. Genetic organization of the chromosome region surrounding mecA in clinical staphylococcal strains: role of IS431-mediated mecI deletion in expression of resistance in mecAcarrying, low-level methicillin-resistant Staphylococcus haemolyticus. Antimicrob. Agents Chemother. 45:1955-1963. (Pubitemid 32591683)
89. Katayama, Y., H. Z. Zhang, and H. F. Chambers. 2003. Effect of disruption of Staphylococcus aureus PBP4 gene on resistance to beta-lactam antibiotics. Microb. Drug Resist. 9:329-336.
90. Katayama, Y., H. Z. Zhang, D. Hong, and H. F. Chambers. 2003. Jumping the barrier to beta-lactam resistance in Staphylococcus aureus. J. Bacteriol. 185:5465-5472.
91. Kattan, J. N., M. V. Villegas, and J. P. Quinn. 2008. New developments in carbapenems. Clin. Microbiol. Infect. 14:1102-1111.
92. Khan, S. A., and R. P. Novick. 1983. Complete nucleotide sequence of pT181, a tetracycline-resistance plasmid from Staphylococcus aureus. Plasmid 10:251-259.
93. Koch, A. L. 2003. Bacterial wall as target for attack: past, present, and future research. Clin. Microbiol. Rev. 16:673-687.
94. Kollef, M. H. 2007. Limitations of vancomycin in the management of resistant staphylococcal infections. Clin. Infect. Dis. 45(Suppl. 3):S191-S195.
95. Komatsuzawa, H., G. H. Choi, T. Fujiwara, Y. Huang, K. Ohta, M. Sugai, and H. Suginaka. 2000. Identification of a fmtA-like gene that has similarity to other PBPs and beta-lactamases in Staphylococcus aureus. FEMS Microbiol. Lett. 188:35-39.
96. Komatsuzawa, H., K. Ohta, T. Fujiwara, G. H. Choi, H. Labischinski, and M. Sugai. 2001. Cloning and sequencing of the gene, fmtC, which affects oxacillin resistance in methicillin-resistant Staphylococcus aureus. FEMS Microbiol. Lett. 203:49-54. (Pubitemid 32830992)
97. Komatsuzawa, H., K. Ohta, H. Labischinski, M. Sugai, and H. Suginaka. 1999. Characterization of fmtA, a gene that modulates the expression of methicillin resistance in Staphylococcus aureus. Antimicrob. Agents Chemother. 43:2121-2125. (Pubitemid 29421187)
98. Komatsuzawa, H., K. Ohta, M. Sugai, T. Fujiwara, P. Glanzmann, B. Berger-Bachi, and H. Suginaka. 2000. Tn551-mediated insertional inactivation of the fmtB gene encoding a cell wall-associated protein abolishes methicillin resistance in Staphylococcus aureus. J. Antimicrob. Chemother. 45:421-431. (Pubitemid 30199133)
99. Komatsuzawa, H., M. Sugai, K. Ohta, T. Fujiwara, S. Nakashima, J. Suzuki, C. Y. Lee, and H. Suginaka. 1997. Cloning and characterization of the fmt gene which affects the methicillin resistance level and autolysis in the presence of Triton X-100 in methicillin-resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 41:2355-2361. (Pubitemid 27467540)
100. Kurazono, M., T. Ida, K. Yamada, Y. Hirai, T. Maruyama, E. Shitara, and M. Yonezawa. 2004. In vitro activities of ME1036 (CP5609), a novel parenteral carbapenem, against methicillin-resistant staphylococci. Antimicrob. Agents Chemother. 48:2831-2837.
101. Kuroda, M., H. Kuroda, T. Oshima, F. Takeuchi, H. Mori, and K. Hiramatsu. 2003. Two-component system VraSR positively modulates the regulation of cell-wall biosynthesis pathway in Staphylococcus aureus. Mol. Microbiol. 49:807-821. (Pubitemid 36918698)
102. Kuroda, M., T. Ohta, I. Uchiyama, T. Baba, H. Yuzawa, I. Kobayashi, L. Cui, A. Oguchi, K. Aoki, Y. Nagai, J. Lian, T. Ito, M. Kanamori, H. Matsumaru, A. Maruyama, H. Murakami, A. Hosoyama, Y. Mizutani-Ui, N. K. Takahashi, T. Sawano, R. Inoue, C. Kaito, K. Sekimizu, H. Hirakawa, S. Kuhara, S. Goto, J. Yabuzaki, M. Kanehisa, A. Yamashita, K. Oshima, K. Furuya, C. Yoshino, T. Shiba, M. Hattori, N. Ogasawara, H. Hayashi, and K. Hiramatsu. 2001. Whole genome sequencing of methicillin-resistant Staphylococcus aureus. Lancet 357:1225-1240.
103. Lappchen, T., V. A. Pinas, A. F. Hartog, G. J. Koomen, C. Schaffner-Barbero, J. M. Andreu, D. Trambaiolo, J. Lowe, A. Juhem, A. V. Popov, and T. den Blaauwen. 2008. Probing FtsZ and tubulin with C8-substituted GTP analogs reveals differences in their nucleotide binding sites. Chem. Biol. 15:189-199.
104. Lewis, R. A., and K. G. Dyke. 2000. MecI represses synthesis from the beta-lactamase operon of Staphylococcus aureus. J. Antimicrob. Chemother. 45:139-144.
105. Lim, D., and N. C. Strynadka. 2002. Structural basis for the beta lactam resistance of PBP2a from methicillin-resistant Staphylococcus aureus. Nat. Struct. Biol. 9:870-876.
106. Liu, C. I., G. Y. Liu, Y. Song, F. Yin, M. E. Hensler, W. Y. Jeng, V. Nizet, A. H. Wang, and E. Oldfield. 2008. A cholesterol biosynthesis inhibitor blocks Staphylococcus aureus virulence. Science 319:1391-1394.
107. Lo, T. S., J. M. Welch, A. M. Alonto, and E. A. Vicaldo-Alonto. 2008. A review of the carbapenems in clinical use and clinical trials. Recent Patents Anti-Infect. Drug Disc. 3:123-131.
108. Loffler, C. A., and C. Macdougall. 2007. Update on prevalence and treatment of methicillin-resistant Staphylococcus aureus infections. Expert Rev. Anti-Infect. Ther. 5:961-981.
109. Loughman, J. A., S. A. Fritz, G. A. Storch, and D. A. Hunstad. 2009. Virulence gene expression in human community-acquired Staphylococcus aureus infection. J. Infect. Dis. 199:294-301.
110. Lovering, A. L., L. H. de Castro, D. Lim, and N. C. Strynadka. 2007. Structural insight into the transglycosylation step of bacterial cell-wall biosynthesis. Science 315:1402-1405.
111. Lowy, F. D. 2007. Secrets of a superbug. Nat. Med. 13:1418-1420.
112. Lu, W. P., Y. Sun, M. D. Bauer, S. Paule, P. M. Koenigs, and W. G. Kraft. 1999. Penicillin-binding protein 2a from methicillin-resistant Staphylococcus aureus: kinetic characterization of its interactions with beta-lactams using electrospray mass spectrometry. Biochemistry 38:6537-6546.
113. Luong, T. T., S. Ouyang, K. Bush, and C. Y. Lee. 2002. Type 1 capsule genes of Staphylococcus aureus are carried in a staphylococcal cassette chromosome genetic element. J. Bacteriol. 184:3623-3629.
114. Maki, H., T. Yamaguchi, and K. Murakami. 1994. Cloning and characterization of a gene affecting the methicillin resistance level and the autolysis rate in Staphylococcus aureus. J. Bacteriol. 176:4993-5000. (Pubitemid 24253739)
115. Maruyama, T., Y. Kano, Y. Yamamoto, M. Kurazono, K. Iwamatsu, K. Atsumi, and E. Shitara. 2007. Synthesis and SAR study of novel 7-(pyridinium-3-yl)- carbonyl imidazo[5,1-b]thiazol-2-yl carbapenems. Bioorg. Med. Chem. 15:392-402.
116. Massova, I., and S. Mobashery. 1998. Kinship and diversification of bacterial penicillin-binding proteins and beta-lactamases. Antimicrob. Agents Chemother. 42:1-17.
117. McAleese, F., S. W. Wu, K. Sieradzki, P. Dunman, E. Murphy, S. Projan, and A. Tomasz. 2006. Overexpression of genes of the cell wall stimulon in clinical isolates of Staphylococcus aureus exhibiting vancomycin-intermediate-S. aureus-type resistance to vancomycin. J. Bacteriol. 188:1120-1133.
118. McCallum, N., G. Spehar, M. Bischoff, and B. Berger-Bachi. 2006. Strain dependence of the cell wall-damage induced stimulon in Staphylococcus aureus. Biochim. Biophys. Acta 1760:1475-1481.
119. McKinney, T. K., V. K. Sharma, W. A. Craig, and G. L. Archer. 2001. Transcription of the gene mediating methicillin resistance in Staphylococcus aureus (mecA) is corepressed but not coinduced by cognate mecA and beta-lactamase regulators. J. Bacteriol. 183:6862-6868.
120. Memmi, G., S. R. Filipe, M. G. Pinho, Z. Fu, and A. Cheung. 2008. Staphylococcus aureus PBP 4 is essential for β-lactam resistance in communityacquired methicillin-resistant strains. Antimicrob. Agents Chemother. 52: 3955-3966.
121. Meroueh, S. O., K. Z. Bencze, D. Hesek, M. Lee, J. F. Fisher, T. L. Stemmler, and S. Mobashery. 2006. Three-dimensional structure of the bacterial cell wall peptidoglycan. Proc. Natl. Acad. Sci. USA 103:4404-4409.
122. Millar, B. C., B. D. Prendergast, and J. E. Moore. 2008. Communityassociated MRSA (CA-MRSA): an emerging pathogen in infective endocarditis. J. Antimicrob. Chemother. 61:1-7.
123. Moellering, R. C. 2008. Current treatment options for community-acquired methicillin-resistant Staphylococcus aureus infection. Clin. Infect. Dis. 46: 1032-1037.
124. Moisan, H., M. Pruneau, and F. Malouin. 2008. Binding of ceftaroline (CPT) to penicillin-binding proteins (PBPs) of Streptococcus pneumoniae (SPN) and methicillin-resistant Staphylococcus aureus (MRSA), poster C1-183. Abstr. 48th Annu. Intersci. Conf. Antimicrob. Agents. Chemother. (ICAAC)/Infect. Dis. Soc. Am. (IDSA) 46th Annu. Meet. American Society for Microbiology and Infectious Diseases Society of America, Washington, DC.
125. Mongkolrattanothai, K., S. Boyle, T. V. Murphy, and R. S. Daum. 2004. Novel non-mecA-containing staphylococcal chromosomal cassette composite island containing pbp4 and tagF genes in a commensal staphylococcal species: a possible reservoir for antibiotic resistance islands in Staphylococcus aureus. Antimicrob. Agents Chemother. 48:1823-1836. (Pubitemid 38544395)
126. Moreillon, P. 2008. New and emerging treatment of Staphylococcus aureus infections in the hospital setting. Clin. Microbiol. Infect. 14(Suppl. 3):32-41.
127. Murakami, K., and A. Tomasz. 1989. Involvement of multiple genetic determinants in high-level methicillin resistance in Staphylococcus aureus. J. Bacteriol. 171:874-879.
128. Murthy, B., and A. Schmitt-Hoffmann. 2008. Pharmacokinetics and pharmacodynamics of ceftobiprole, an anti-MRSA cephalosporin with broadspectrum activity. Clin. Pharmacokinet. 47:21-33.
129. Mushtaq, S., M. Warner, Y. Ge, K. Kaniga, and D. M. Livermore. 2007. In vitro activity of ceftaroline (PPI-0903M, T-91825) against bacteria with defined resistance mechanisms and phenotypes. J. Antimicrob. Chemother. 60:300-311.
130. Nagura, J., K. Kijima, M. Kurazono, S. Takahata, T. Sugano, Y. Tanaka, Y. Hirai, K. Yamada, Y. Takayama, E. Shitara, and M. Yonezawa. 2005. Therapeutic effect of ME1036 on endocarditis experimentally induced by methicillin-resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 49:3526-3528. (Pubitemid 41060610)
131. Niemeyer, D. M., M. J. Pucci, J. A. Thanassi, V. K. Sharma, and G. L. Archer. 1996. Role of mecA transcriptional regulation in the phenotypic expression of methicillin resistance in Staphylococcus aureus. J. Bacteriol. 178:5464-5471.
132. Noel, G. J., K. Bush, P. Bagchi, J. Ianus, and R. S. Strauss. 2008. A randomized, double-blind trial comparing ceftobiprole medocaril with vancomycin plus ceftazidime for the treatment of patients with complicated skin and skin-structure infections. Clin. Infect. Dis. 46:647-655.
133. Noel, G. J., R. S. Strauss, K. Amsler, M. Heep, R. Pypstra, and J. S. Solomkin. 2008. Results of a double-blind, randomized trial of ceftobiprole treatment of complicated skin and skin structure infections caused by grampositive bacteria. Antimicrob. Agents Chemother. 52:37-44.
134. Nubel, U., P. Roumagnac, M. Feldkamp, J. H. Song, K. S. Ko, Y. C. Huang, G. Coombs, M. Ip, H. Westh, R. Skov, M. J. Struelens, R. V. Goering, B. Strommenger, A. Weller, W. Witte, and M. Achtman. 2008. Frequent emergence and limited geographic dispersal of methicillin-resistant Staphylococcus aureus. Proc. Natl. Acad. Sci. USA 105:14130-14135.
135. Nygaard, T. K., F. R. DeLeo, and J. M. Voyich. 2008. Community-associated methicillin-resistant Staphylococcus aureus skin infections: advances toward identifying the key virulence factors. Curr. Opin. Infect. Dis. 21:147-152.
136. Page, M. G. 2006. Anti-MRSA beta-lactams in development. Curr. Opin. Pharmacol. 6:480-485.
137. Page, M. G. 2007. Emerging cephalosporins. Expert Opin. Emerg. Drugs 12:511-524.
138. Pan, A., S. Lorenzotti, and A. Zoncada. 2008. Registered and investigational drugs for the treatment of methicillin-resistant Staphylococcus aureus infection. Recent Patents Anti-Infect. Drug Disc. 3:10-33.
139. Park, J. W., C. H. Kim, J. H. Kim, B. R. Je, K. B. Roh, S. J. Kim, H. H. Lee, J. H. Ryu, J. H. Lim, B. H. Oh, W. J. Lee, N. C. Ha, and B. L. Lee. 2007. Clustering of peptidoglycan recognition protein-SA is required for sensing lysine-type peptidoglycan in insects. Proc. Natl. Acad. Sci. USA 104:6602-6607.
140. Parvez, M. A., H. Shibata, T. Nakano, S. Niimi, N. Fujii, N. Arakaki, and T. Higuti. 2008. No relationship exists between PBP 2a amounts expressed in different MRSA strains obtained clinically and their beta-lactam MIC values. J. Med. Investig. 55:246-253.
141. Payne, D. J., M. N. Gwynn, D. J. Holmes, and D. L. Pompliano. 2007. Drugs for bad bugs: confronting the challenges of antibacterial discovery. Nat. Rev. Drug Discov. 6:29-40.
142. Pinho, M. G., H. de Lencastre, and A. Tomasz. 2001. An acquired and a native penicillin-binding protein cooperate in building the cell wall of drugresistant staphylococci. Proc. Natl. Acad. Sci. USA 98:10886-10891.
143. Pinho, M. G., and J. Errington. 2003. Dispersed mode of Staphylococcus aureus cell wall synthesis in the absence of the division machinery. Mol. Microbiol. 50:871-881.
144. Popovich, K. J., B. Hota, and R. A. Weinstein. 2008. Treatment of community-associated methicillin-resistant Staphylococcus aureus. Curr. Infect. Dis. Rep. 10:411-420.
145. Popovich, K. J., R. A. Weinstein, and B. Hota. 2008. Are community-associated methicillin-resistant Staphylococcus aureus (MRSA) strains replacing traditional nosocomial MRSA strains? Clin. Infect. Dis. 46:787-794.
146. Projan, S. J., and P. A. Bradford. 2007. Late stage antibacterial drugs in the clinical pipeline. Curr. Opin. Microbiol. 10:441-446.
147. Pucci, M. J., and T. J. Dougherty. 2002. Direct quantitation of the numbers of individual penicillin-binding proteins per cell in Staphylococcus aureus. J. Bacteriol. 184:588-591.
148. Queenan, A. M., W. Shang, M. Kania, M. G. Page, and K. Bush. 2007. Interactions of ceftobiprole with beta-lactamases from molecular classes A to D. Antimicrob. Agents Chemother. 51:3089-3095.
149. Raju, S., R. Kelmani Chandrakanth, and S. A. Patil. 2007. High-level oxacillin and gentamycin resistance with reduced susceptibility to vancomycin in Staphylococcus aureus-carrying mecA and femA gene complex. Curr. Microbiol. 54:429-434. (Pubitemid 46790851)
150. Rasmussen, F. 2007. Discovery, isolation, production and introduction of penicillin for veterinary use in Denmark during World War II. Vet. History 13:339-353.
151. Riccobene, T., E. Fang, and D. Thye. 2008. A single- and multiple-dose study to determine the safety, tolerability, and pharmacokinetics (PK) of ceftaroline (CPT) administered by intramuscular (IM) injection to healthy subjects, poster A-1888. Abstr. 48th Annu. Intersci. Conf. Antimicrob. Agents. Chemother. (ICAAC)/Infect. Dis. Soc. Am. (IDSA) 46th Annu. Meet. American Society for Microbiology and Infectious Diseases Society of America, Washington, DC.
152. Richards, M. J., J. R. Edwards, D. H. Culver, R. P. Gaynes, et al. 1999. Nosocomial infections in pediatric intensive care units in the United States. Pediatrics 103:e39.
153. Richards, M. J., J. R. Edwards, D. H. Culver, R. P. Gaynes, et al. 1999. Nosocomial infections in medical intensive care units in the United States. Crit. Care Med. 27:887-892.
154. Rohrer, S., and B. Berger-Bachi. 2003. FemABX peptidyl transferases: a link between branched-chain cell wall peptide formation and beta-lactam resistance in gram-positive cocci. Antimicrob. Agents Chemother. 47:837-846.
155. Ross, J. E., T. R. Fritsche, H. S. Sader, and R. N. Jones. 2007. Oxazolidinone susceptibility patterns for 2005: International Report from the Zyvox Annual Appraisal of Potency and Spectrum Study. Int. J. Antimicrob. Agents 29:295-301.
156. Royet, J., and R. Dziarski. 2007. Peptidoglycan recognition proteins: pleiotropic sensors and effectors of antimicrobial defences. Nat. Rev. Microbiol. 5:264-277.
157. Ryffel, C., F. H. Kayser, and B. Berger-Bachi. 1992. Correlation between regulation of mecA transcription and expression of methicillin resistance in staphylococci. Antimicrob. Agents Chemother. 36:25-31.
158. Ryffel, C., A. Strassle, F. H. Kayser, and B. Berger-Bachi. 1994. Mechanisms of heteroresistance in methicillin-resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 38:724-728.
159. Sader, H. S., T. R. Fritsche, and R. N. Jones. 2008. Antimicrobial activities of ceftaroline and ME1036 tested against clinical strains of communityacquired methicillin-resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 52:1153-1155.
160. Sakoulas, G., and R. C. Moellering. 2008. Increasing antibiotic resistance among methicillin-resistant Staphylococcus aureus strains. Clin. Infect. Dis. 46(Suppl. 5):S360-S367.
161. Saravolatz, L. D., J. Pawlak, and L. Johnson. 2008. In vitro activity of ceftaroline against CA-MRSA, VISA, VRSA and daptomycin-non-susceptible Staphylococcus aureus (DNSSA), poster C1-162. Abstr. 48th Annu. Intersci. Conf. Antimicrob. Agents. Chemother. (ICAAC)/Infect. Dis. Soc. Am. (IDSA) 46th Annu. Meet. American Society for Microbiology and Infectious Diseases Society of America, Washington, DC.
162. Sauvage, E., F. Kerff, M. Terrak, J. A. Ayala, and P. Charlier. 2008. The penicillin-binding proteins: structure and role in peptidoglycan biosynthesis. FEMS Microbiol. Rev. 32:234-258.
163. Schmitt-Hoffmann, A., L. Nyman, B. Roos, M. Schleimer, J. Sauer, N. Nashed, T. Brown, A. Man, and E. Weidekamm. 2004. Multiple-dose pharmacokinetics and safety of a novel broad-spectrum cephalosporin (BAL5788) in healthy volunteers. Antimicrob. Agents Chemother. 48:2576-2580.
164. Schmitt-Hoffmann, A., B. Roos, M. Schleimer, J. Sauer, A. Man, N. Nashed, T. Brown, A. Perez, E. Weidekamm, and P. Kovacs. 2004. Single-dose pharmacokinetics and safety of a novel broad-spectrum cephalosporin (BAL5788) in healthy volunteers. Antimicrob. Agents Chemother. 48:2570-2575.
165. Stepanovic, S., V. Dimitrijevic, D. Vukovic, I. Dakic, B. Savic, and M. Svabic-Vlahovic. 2001. Staphylococcus sciuri as a part of skin, nasal and oral flora in healthy dogs. Vet. Microbiol. 82:177-185.
166. Suzuki, E., K. Kuwahara-Arai, J. F. Richardson, and K. Hiramatsu. 1993. Distribution of mec regulator genes in methicillin-resistant Staphylococcus clinical strains. Antimicrob. Agents Chemother. 37:1219-1226.
167. Takeuchi, F., S. Watanabe, T. Baba, H. Yuzawa, T. Ito, Y. Morimoto, M. Kuroda, L. Cui, M. Takahashi, A. Ankai, S. Baba, S. Fukui, J. C. Lee, and K. Hiramatsu. 2005. Whole-genome sequencing of Staphylococcus haemolyticus uncovers the extreme plasticity of its genome and the evolution of human-colonizing staphylococcal species. J. Bacteriol. 187:7292-7308.
168. Thumanu, K., J. Cha, J. F. Fisher, R. Perrins, S. Mobashery, and C. Wharton. 2006. Discrete steps in sensing of beta-lactam antibiotics by the BlaR1 protein of the methicillin-resistant Staphylococcus aureus bacterium. Proc. Natl. Acad. Sci. USA 103:10630-10635.
169. Toh, S. M., L. Xiong, C. A. Arias, M. V. Villegas, K. Lolans, J. Quinn, and A. S. Mankin. 2007. Acquisition of a natural resistance gene renders a clinical strain of methicillin-resistant Staphylococcus aureus resistant to the synthetic antibiotic linezolid. Mol. Microbiol. 64:1506-1514.
170. Tomasz, A., H. B. Drugeon, H. M. de Lencastre, D. Jabes, L. McDougall, and J. Bille. 1989. New mechanism for methicillin resistance in Staphylococcus aureus: clinical isolates that lack the PBP 2a gene and contain normal penicillin-binding proteins with modified penicillin-binding capacity. Antimicrob. Agents Chemother. 33:1869-1874.
171. Tu Quoc, P. H., P. Genevaux, M. Pajunen, H. Savilahti, C. Georgopoulos, J. Schrenzel, and W. L. Kelley. 2007. Isolation and characterization of biofilm formation-defective mutants of Staphylococcus aureus. Infect. Immun. 75:1079-1088.
172. Uda, T., K. Takemoto, K. Fujimoto, K. Eguchi, and K. Kanazawa. 2008. Post-antibiotic effect (PAE) of SMP-601 (PZ-601) against Staphylococcus aureus including MRSA and VISA, poster F1-361. Abstr. 48th Annu. Intersci. Conf. Antimicrob. Agents. Chemother. (ICAAC)/Infect. Dis. Soc. Am. (IDSA) 46th Annu. Meet. American Society for Microbiology and Infectious Diseases Society of America, Washington, DC.
173. Utaida, S., P. M. Dunman, D. Macapagal, E. Murphy, S. J. Projan, V. K. Singh, R. K. Jayaswal, and B. J. Wilkinson. 2003. Genome-wide transcriptional profiling of the response of Staphylococcus aureus to cell-wall-active antibiotics reveals a cell-wall-stress stimulon. Microbiology 149:2719-2732.
174. van Heijenoort, J. 2001. Formation of the glycan chains in the synthesis of bacterial peptidoglycan. Glycobiology 11:25R-36R.
175. van Heijenoort, J., and L. Gutmann. 2000. Correlation between the structure of the bacterial peptidoglycan monomer unit, the specificity of transpeptidation, and susceptibility to beta-lactams. Proc. Natl. Acad. Sci. USA 97:5028-5030.
176. Villegas-Estrada, A., M. Lee, D. Hesek, S. B. Vakulenko, and S. Mobashery. 2008. Co-opting the cell wall in fighting methicillin-resistant Staphylococcus aureus: potent inhibition of PBP 2a by two anti-MRSA beta-lactam antibiotics. J. Am. Chem. Soc. 130:9212-9213.
177. Vollmer, W., D. Blanot, and M. A. de Pedro. 2008. Peptidoglycan structure and architecture. FEMS Microbiol. Rev. 32:149-167.
178. von Nussbaum, F., M. Brands, B. Hinzen, S. Weigand, and D. Habich. 2006. Antibacterial natural products in medicinal chemistry-exodus or revival? Angew. Chem. Int. Ed. Engl. 45:5072-5129.
179. Waxman, D. J., and J. L. Strominger. 1983. Penicillin-binding proteins and the mechanism of action of beta-lactam antibiotics. Annu. Rev. Biochem. 52:825-869.
180. Weigel, L. M., D. B. Clewell, S. R. Gill, N. C. Clark, L. K. McDougal, S. E. Flannagan, J. F. Kolonay, J. Shetty, G. E. Killgore, and F. C. Tenover. 2003. Genetic analysis of a high-level vancomycin-resistant isolate of Staphylococcus aureus. Science 302:1569-1571.
181. Wright, G. D., and A. D. Sutherland. 2007. New strategies for combating multidrug-resistant bacteria. Trends Mol. Med. 13:260-267.
182. Wu, S., H. de Lencastre, A. Sali, and A. Tomasz. 1996. A phosphoglucomutase-like gene essential for the optimal expression of methicillin resistance in Staphylococcus aureus: molecular cloning and DNA sequencing. Microb. Drug Resist. 2:277-286.
183. Wu, S. W., H. de Lencastre, and A. Tomasz. 2001. Recruitment of the mecA gene homologue of Staphylococcus sciuri into a resistance determinant and expression of the resistant phenotype in Staphylococcus aureus. J. Bacteriol. 183:2417-2424.
184. Xiong, Y. Q., Y. Li, W. Abdel Hady, D. Biek, Y. Ge, and A. S. Bayer. 2008. Real-time evaluation of a new carbapenem, ME1036, in a rat Staphylococcus aureus endocarditis (IE) model using in vivo bioluminescent imaging, poster F1-343. Abstr. 48th Annu. Intersci. Conf. Antimicrob. Agents. Chemother. (ICAAC)/Infect. Dis. Soc. Am. (IDSA) 46th Annu. Meet. American Society for Microbiology and Infectious Diseases Society of America, Washington, DC.
185. Yuan, Y., S. Fuse, B. Ostash, P. Sliz, D. Kahne, and S. Walker. 2008. Structural analysis of the contacts anchoring moenomycin to peptidoglycan glycosyltransferases and implications for antibiotic design. ACS Chem. Biol. 3:429-436.
186. Zapun, A., C. Contreras-Martel, and T. Vernet. 2008. Penicillin-binding proteins and beta-lactam resistance. FEMS Microbiol. Rev. 32:361-385.
187. Zetola, N., J. S. Francis, E. L. Nuermberger, and W. R. Bishai. 2005. Community-acquired methicillin-resistant Staphylococcus aureus: an emerging threat. Lancet Infect. Dis. 5:275-286.
188. Zhang, H. Z., C. J. Hackbarth, K. M. Chansky, and H. F. Chambers. 2001. A proteolytic transmembrane signaling pathway and resistance to betalactams in staphylococci. Science 291:1962-1965.
189. Zhou, Y., A. Antignac, S. W. Wu, and A. Tomasz. 2008. Penicillin-binding proteins and cell wall composition in beta-lactam-sensitive and -resistant strains of Staphylococcus sciuri. J. Bacteriol. 190:508-514. (Pubitemid 351360066)