Chapter 7 : Resistance Mediated by Penicillin-Binding Proteins

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Resistance Mediated by Penicillin-Binding Proteins, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555815615/9781555813031_Chap07-1.gif /docserver/preview/fulltext/10.1128/9781555815615/9781555813031_Chap07-2.gif


The transpeptidases are members of the family of penicillin-binding proteins (PBPs), which have become known as the targets of β-lactam antibiotics. PBPs perform a variety of critical functions for the bacterial cell. PBPs are found in all pathogenic bacteria except those of the genus , which do not have a cell wall. Reduced expression of PBP2 (type B, assignment not certain) is one of the most frequently observed mechanisms of resistance to carbapenems. PBP2 (type B4) and PBP3 (type B5) have been specifically implicated in resistance towards β-lactams. Increased expression of PBP4 (type C2) has been implicated in resistance to both β-lactams and glycopeptides. Hakenbeck et al. implicated the D,D-carboxypeptidase PBP3 (type C3) in resistance. PCR-based methods for the detection of antibiotic resistance are becoming increasingly important with the expanding use of molecular techniques for bacteriological diagnosis. Antibody-based tests have also been investigated for detection of methicillin resistance in staphylococci. There are several experimental β-lactams now known to be potent inhibitors of the staphylococcal type B1 PBP that is the primary determinant of β-lactam resistance in these organisms, of which ceftobiprole is the most advanced in clinical development. An understanding of the mechanism of methicillin resistance has led to the discovery of accessory factors that influence the level and nature of methicillin resistance.

Citation: Page M. 2007. Resistance Mediated by Penicillin-Binding Proteins, p 81-99. In Bonomo R, Tolmasky M (ed), Enzyme-Mediated Resistance to Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555815615.ch7
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of Figure 7.1
Figure 7.1

Comparison of PBP profiles of selected organisms and pattern alterations commonly encountered in resistant organisms. The PBPs have been labeled by incubation of membranes derived by sonication of cultures of the indicated organisms with radiolabeled benzylpenicillin and then resolution of the proteins by standard sodium dodecyl sulfate-polyacrylamide gel electrophoresis. From left to right:, MRSA, , penicillin susceptible (Pen) and an example of a penicillin-resistant (Pen) isolate where loss of affinity makes some PBPs disappear, and , ampicillin-susceptible (Amp) and an example of an ampicillin-resistant (Amp) isolate where loss of affinity of PBP1 and PBP4 as well as overexpression of PBP5 are evident.

Citation: Page M. 2007. Resistance Mediated by Penicillin-Binding Proteins, p 81-99. In Bonomo R, Tolmasky M (ed), Enzyme-Mediated Resistance to Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555815615.ch7
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Untitled

Citation: Page M. 2007. Resistance Mediated by Penicillin-Binding Proteins, p 81-99. In Bonomo R, Tolmasky M (ed), Enzyme-Mediated Resistance to Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555815615.ch7
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 7.2
Figure 7.2

Location of mutations in PBPs conferring resistance to β-lactams. Regions from the sequences of susceptible proteins are shown, with the residues that are mutated in resistant isolates shown in bold and boxed. The highly conserved residues that comprise parts of the active site ( ) are shown in bold. The organisms denoted are (Efc), (Hin), (Hpy), (Nme), (Sau), and (Spn).

Citation: Page M. 2007. Resistance Mediated by Penicillin-Binding Proteins, p 81-99. In Bonomo R, Tolmasky M (ed), Enzyme-Mediated Resistance to Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555815615.ch7
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Ameyama, S.,, S. Onodera,, M. Takahata,, S. Minami,, N. Maki,, K. Endo,, H. Goto,, H. Suzuki, and, Y. Oishi. 2002. Mosaic-like structure of penicillin-binding protein 2 gene ( penA) in clinical isolates of Neisseria gonorrhoeae with reduced susceptibility to cefixime. Antimicrob. Agents Chemother. 46: 37443749.
2. Antignac, A.,, J.-M. Alonso, and, M.-K. Taha. 2000. Update on the resistance of Neisseria meningitidis to antibiotics, based on the strains tested at the French National Reference Center in 1998. Antibiotiques 2: 241245.
3. Antignac, A.,, I. G. Boneca,, J.-C. Rousselle,, A. Namane,, J.-P. Carlier,, J. A. Vazquez,, A. Fox,, J.-M. Alonso, and, M.-K. Taha. 2003. Correlation between alterations of the penicillin-binding protein 2 and modifications of the peptidoglycan structure in Neisseria meningitidis with reduced susceptibility to penicillin G. J. Biol. Chem. 278: 3152931535.
4. Antignac, A.,, P. Kriz,, G. Tzanakaki,, J.-M. Alonso, and, M.-K. Taha. 2001. Polymorphism of Neisseria meningitidis penA gene associated with reduced susceptibility to penicillin. J. Antimicrob. Chemother. 47: 285296.
5. Arreaza, L.,, B. Alcala,, C. Salcedo,, L. de la Fuente, and, J. A. Vazquez. 2003. Dynamics of the penA gene in sero-group C meningococcal strains. J. Infect. Dis. 187: 10101014.
6. Asahi, Y., and, K. Ubukata. 1998. Association of a Thr-371 substitution in a conserved amino acid motif of penicillin-binding protein 1A with penicillin resistance of Streptococcus pneumoniae. Antimicrob. Agents Chemother. 42: 22672273.
7. Bellido, F.,, C. Veuthey,, J. Blaser,, A. Bauernfeind, and, J. C. Pechere. 1990. Novel resistance to imipenem associated with an altered PBP-4 in a Pseudomonas aeruginosa clinical isolate. J. Antimicrob. Chemother. 25: 5768.
8. Berger-Bachi, B., and, S. Rohrer. 2002. Factors influencing methicillin resistance in staphylococci. Arch. Microbiol. 178: 165171.
9. Bhakta, S., and, J. Basu. 2002. Overexpression, purification and biochemical characterization of a class A high-molecular-mass penicillin-binding protein (PBP), PBP1* and its soluble derivative from Mycobacterium tuberculosis. Biochem. J. 361: 635639.
10. Bowler, L. E.,, Q. Y. Zhang,, J. Y. Riou, and, B. G. Spratt. 1994. Interspecies recombination between the penA genes of Neisseria meningitidis and commensal Neisseria species during the emergence of penicillin resistance in N. meningitidis: natural events and laboratory simulation. J. Bacteriol. 176: 333337.
11. Brannigan, J. A.,, I. A. Tirodimos,, Q. Y. Zhang,, C. G. Dowson, and, B. G. Spratt. 1990. Insertion of an extra amino acid is the main cause of the low affinity of penicillin-binding protein 2 in penicillin-resistant strains of Neisseria gonorrhoeae. Mol. Microbiol. 4: 913919.
12. Chalkley, L., and, I. Van der Westhuyzen. 1993. Penicillin-binding proteins of clostridia. Curr. Microbiol. 26: 109112.
13. Chalkley, L. J.,, S. van Vuuren,, R. C. Ballard, and, P. L. Botha. 1995. Characterization of penA and tetM resistance genes of Neisseria gonorrhoeae isolated in southern Africa— epidemiological monitoring and resistance development. S. Afr. Med. J. 85: 775780.
14. Chambers, H. F.,, M. J. Sachdeva, and, C. J. Hackbarth. 1994. Kinetics of penicillin binding to penicillin-binding proteins of Staphylococcus aureus. Biochem. J. 301: 139144.
15. Chen, H. Y., and, J. D. Williams. 1987. Penicillin-binding proteins in Streptococcus faecalis and S. faecium. J. Med. Microbiol. 23: 141147.
16. Chittock, R. S.,, S. Ward,, A.-S. Wilkinson,, P. Caspers,, B. Mensch,, M.G. P. Page, and, C. W. Wharton. 1999. Hydrogen bonding and protein perturbation in β-lactam acyl-enzymes of Streptococcus pneumoniae penicillin-binding protein PBP2x. Biochem. J. 338: 153159.
17. Contreras-Martel, C.,, V. Job,, A. M. Di Guilmi,, T. Vernet,, O. Dideberg, and, A. Dessen. 2006. Crystal structure of penicillin-binding protein 1a (PBP1a) reveals a mutational hotspot implicated in β-lactam resistance in Streptococcus pneumoniae. J. Mol. Biol. 355: 684696.
18. Dessen, A.,, N. Mouz,, E. Gordon,, J. Hopkins, and, O. Dideberg. 2001. Crystal structure of PBP2x from a highly penicillin-resistant Streptococcus pneumoniae clinical isolate. A mosaic framework containing 83 mutations. J. Biol. Chem. 276: 4510645112.
19. Dore, M. P.,, D. Y. Graham, and, A. R. Sepulveda. 1999. Different penicillin-binding protein profiles in amoxicillin-resistant Helicobacter pylori. Helicobacter 4: 154161.
20. Dougherty, T. J. 1983. Peptidoglycan biosynthesis in Neisseria gonorrhoeae strains sensitive and intrinsically resistant to β-lactam antibiotics. J. Bacteriol. 153: 429435.
21. Dougherty, T. J. 1986. Genetic analysis and penicillin-binding protein alterations in Neisseria gonorrhoeae with chromosomally mediated resistance. Antimicrob. Agents Chemother. 30: 649652.
22. Dougherty, T. J.,, A. E. Koller, and, A. Tomasz. 1980. Penicillin-binding proteins of penicillin-susceptible and intrinsically resistant Neisseria gonorrhoeae. Antimicrob. Agents Chemother. 18: 730737.
23. Dowson, C. G.,, A. E. Jephcott,, K. R. Gough, and, B. G. Spratt. 1989. Penicillin-binding protein 2 genes of non-β-lactamase-producing, penicillin-resistant strains of Neisse-ria gonorrhoeae. Mol. Microbiol. 3: 3541.
24. du Plessis, M.,, A. M. Smith, and, K. P. Klugman. 1999. Application of pbp1A PCR in identification of penicillin-resistant Streptococcus pneumoniae. J. Clin. Microbiol. 37: 628632.
25. Edwards, R., and, D. Greenwood. 1996. Mechanisms responsible for reduced susceptibility to imipenem in Bacteroides fragilis. J. Antimicrob. Chemother. 38: 941951.
26. Fernandez-Cuenca, F.,, L. Martinez-Martinez,, M. C. Conejo,, J. A. Ayala,, E. J. Perea, and, A. Pascual. 2003. Relationship between β-lactamase production, outer membrane protein and penicillin-binding protein profiles on the activity of carbapenems against clinical isolates of Acinetobacter baumannii. J. Antimicrob. Chemother. 51: 565574.
27. Fontana, R.,, A. Grossato,, L. Rossi,, Y. R. Cheng, and, G. Satta. 1985. Transition from resistance to hypersusceptibility to β-lactam antibiotics associated with loss of a low-affinity penicillin-binding protein in a Streptococcus faecium mutant highly resistant to penicillin. Antimicrob. Agents Chemother. 28: 678683.
28. Fontana, R.,, L. Rossi,, Y. C. Rong, and, E. Tonin. 1985. Penicillin-binding proteins and resistance to β-lactam antibiotics in Staphylococcus aureus. Chemioterapia 4: 5355.
29. Fuda, C.,, M. Suvorov,, S. B. Vakulenko, and, S. Mobashery. 2004. The basis for resistance to β-lactam antibiotics by penicillin-binding protein 2a of methicillin-resistant Staphylococcus aureus. J. Biol. Chem. 279: 4080240806.
30. Gaisford, W. C., and, P. E. Reynolds. 1989. Methicillin resistance in Staphylococcus epidermidis. Relationship between the additional penicillin-binding protein and an attachment transpeptidase. Eur. J. Biochem. 185: 211218.
31. Gehrlein, M.,, H. Leying,, W. Cullmann,, S. Wendt, and, W. Opferkuch. 1991. Imipenem resistance in Acinetobacter baumannii is due to altered penicillin-binding proteins. Chemotherapy 37: 405412.
32. Gerberding, J. L.,, C. Miick,, H. H. Liu, and, H. F. Chambers. 1991. Comparison of conventional susceptibility tests with direct detection of penicillin-binding protein 2a in borderline oxacillin-resistant strains of Staphylococcus aureus. Antimicrob. Agents Chemother. 35: 25742579.
33. Gerrits, M. M.,, D. Schuijffel,, A. A. Van Zwet,, E. J. Kuipers,, C. M. J. E. Vandenbroucke-Grauls, and, J. G. Kusters. 2002. Alterations in penicillin-binding protein 1A confer resistance to β-lactam antibiotics in Helicobacter pylori. Antimicrob. Agents Chemother. 46: 22292233.
34. Ghuysen, J. M. 1991. Serine β-lactamases and penicillin-binding proteins. Annu. Rev. Microbiol 45: 3767.
35. Ghuysen, J. M., and, C. Goffin. 1999. Lack of cell wall peptidoglycan versus penicillin sensitivity: new insights into the chlamydial anomaly. Antimicrob. Agents Chemother. 43: 23392344.
36. Glinka, T. W.,, A. Cho,, Z. J. Zhang,, M. Ludwikow,, D. Griffith,, K. Huie,, S. J. Hecker,, M. N. Dudley,, V. J. Lee, and, S. Chamberland. 2000. SAR studies of anti-MRSA non-zwitterionic 3-heteroarylthiocephems. J. Antibiot. 53: 10451052.
37. Godfrey, A. J.,, L. E. Bryan, and, H. R. Rabin. 1981. β-Lactam-resistant Pseudomonas aeruginosa with modified penicillin-binding proteins emerging during cystic fibrosis treatment. Antimicrob. Agents Chemother. 19: 705711.
38. Godfrey, A. J., and, L. E. Bryan. 1982. Mutation of Pseudomonas aeruginosa specifying reduced affinity for penicillin G. Antimicrob. Agents Chemother. 21: 216223.
39. Goffi n C., and, J. M. Ghuysen. 1998. Multimodular penicillin-binding proteins: an enigmatic family of orthologs and paralogs. Microbiol. Mol. Biol. Rev. 62: 10791093.
40. Goffi n, 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: 702738.
41. 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.
42. Gotoh, N.,, K. Nunomura, and, T. Nishino. 1990. Resistance of Pseudomonas aeruginosa to cefsulodin: modification of penicillin-binding protein 3 and mapping of its chromosomal gene. J. Antimicrob. Chemother. 25: 513523.
43. Graves-Woodward, K., and, R. F. Pratt. 1998. Reaction of soluble penicillin-binding protein 2a of methicillin-resistant Staphylococcus aureus with β-lactams and acyclic substrates: kinetics in homogeneous solution. Biochem. J. 332: 755761.
44. Grayson, M. L.,, G. M. Eliopoulos,, C. B. Wennersten,, K. L. Ruoff,, K. Klimm,, F. L. Sapico,, A. S. Bayer, and, R. C. Moellering, Jr. 1991. Comparison of Enterococcus raffinosus with Enterococcus avium on the basis of penicillin susceptibility, penicillin-binding protein analysis, and high-level aminoglycoside resistance. Antimicrob. Agents Chemother. 35: 14081412.
45. Grebe, T., and, R. Hakenbeck. 1996. Penicillin-binding proteins 2b and 2x of Streptococcus pneumoniae are primary resistance determinants for different classes of β-lactam antibiotics. Antimicrob. Agents Chemother. 40: 829834.
46. Gutkind, G. O.,, S. B. Ogueta,, A. C. De Urtiaga,, M. E. Mollerach, and, R. A. De Torres. 1990. Participation of PBP 3 in the acquisition of dicloxacillin resistance in Listeria monocytogenes. J. Antimicrob. Chemother. 25: 751758.
47. Hackbarth, C. J.,, T. Kocagoz,, S. Kocagoz, and, H. F. Chambers. 1995. Point mutations in Staphylococcus aureus PBP 2 gene affect penicillin-binding kinetics and are associated with resistance. Antimicrob. Agents Chemother. 39: 103106.
48. Hakenbeck, R.,, H. Ellerbrok,, T. Briese,, S. Handwerger, and, A. Tomasz. 1986. Penicillin-binding proteins of penicillin-susceptible and -resistant pneumococci: immunological relatedness of altered proteins and changes in peptides carrying the β-lactam binding site. Antimicrob. Agents Chemother. 30: 553558.
49. 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 β-lactam resistance from Streptococcus mitis to Streptococcus pneumoniae. J. Bacteriol. 180: 18311840.
50. Hanaki, H.,, H. Akagi,, Y. Masaru,, T. Otani,, A. Hyodo, and, K. Hiramatsu. 1995. TOC-39, a novel parenteral broad-spectrum cephalosporin with excellent activity against methicillin-resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 39: 11201126.
51. Hartman, B. J., and, A. Tomasz. 1984. Low-affinity penicillin-binding protein associated with β-lactam resistance in Staphylococcus aureus. J. Bacteriol. 158: 513516.
52. Hartman, B. J., and, A. Tomasz. 1986. Expression of methi-cillin resistance in heterogeneous strains of Staphylococcus aureus. Antimicrob. Agents Chemother. 29: 8592.
53. Hatano, T.,, Y. Shintani,, Y. Aga,, S. Shiota,, T. Tsuchiya, and, T. Yoshida. 2000. Phenolic constituents of licorice. VIII. Structures of glicophenone and glicoisoflavanone, and effects of licorice phenolics on methicillin-resistant Staphylococcus aureus. Chem. Pharm. Bull. 48: 12861292.
54. Hatano, T., and, T. Yoshida. 2003. Constituents of Zan-thoxylum fruits and the other herbs and the spices effective on methicillin-resistant Staphylococcus aureus (MRSA). Aroma Res. 4: 384388.
55. Hebeisen, P.,, I. Heinze-Krauss,, P. Angehrn,, P. Hohl,, M. G. P. Page, and, R. L. Then. 2001. In vitro and in vivo properties of Ro 63–9141, a novel broad-spectrum cephalosporin with activity against methicillin-resistant staphylococci. Antimi-crob. Agents Chemother. 45: 825836.
56. Hedberg, M.,, K. Bush,, P. A. Bradford,, N. Bhachech,, C. Edlund,, K. Tuner, and, C. E. Nord. 1996. The role of penicillin-binding proteins for β-lactam resistance in a β-lactamase-producing Bacteroides uniformis strain. Anaerobe 2: 111115.
57. Hedberg, M.,, E. Nagy, and, C. E. Nord. 1997. Role of penicillin-binding proteins in resistance of Bacteroides fragilis group species to β-lactam drugs. Clin. Infect. Dis. 25(Suppl. 2): S270S271.
58. Henze, U. U., and, B. Berger-Baechi. 1996. Penicillin-binding protein 4 overproduction increases β-lactam resistance in Staphylococcus aureus. Antimicrob. Agents Chemother. 40: 21212125.
59. Higashi, Y.,, A. Wakabayashi,, Y. Matsumoto,, Y. Watanabe, and, A. Ohno. 1999. Role of inhibition of penicillin binding proteins and cell wall crosslinking by beta-lactam antibiotics in low- and high-level methicillin resistance of Staphylo-coccus aureus. Chemotherapy 45: 3747.
60. Hujer, A. M.,, M. Kania,, T. Gerken,, V. E. Anderson,, J. Buynak,, X. Ge,, P. Caspers,, M. G. P. Page,, L. B. Rice, and, R. A. Bonomo. 2005. Structure-activity relationships of different β-lactam antibiotics against a soluble form of Entero-coccus faecium PBP5, a type II bacterial transpeptidase. Antimicrob. Agents Chemother 49: 612618.
61. Hussain, Z.,, L. Stoakes,, S. Garrow,, S. Longo,, V. Fitzgerald, and, R. Lannigan. 2000. Rapid detection of mecA-positive and mecA-negative coagulase-negative staphylococci by an anti-penicillin binding protein 2a slide latex agglutination test. J. Clin. Microbiol. 38: 20512054.
62. Imamura, H.,, N. Ohtake,, H. Jona,, A. Shimizu,, M. Moriya,, H. Sato,, Y. Sugimoto,, C. Ikeura,, H. Kiyonaga,, M. Nakano,, R. Nagano,, S. Abe,, K. Yamada,, T. Hashizume, and, H. Morishima. 2001. Dicationic dithiocarbamate carbapenems with anti-MRSA activity. Bioorg. Med. Chem. 9: 15711578.
63. Ishikawa, T.,, N. Matsunaga,, H. Tawada,, N. Kuroda,, Y. Nakayama,, Y. Ishibashi,, M. Tomimoto,, Y. Ikeda,, Y. Tagawa,, Y. Iizawa,, K. Okonogi,, S. Hashiguchi, and, A. Miyake. 2003. TAK-599, a novel N-phosphono type pro-drug of anti-MRSA cephalosporin T-91825: synthesis, phys-icochemical and pharmacological properties. Bioorg. Med. Chem. 11: 24272437.
64. Jabes, D.,, S. Nachman, and, A. Tomasz. 1989. Penicillin-binding protein families: evidence for the clonal nature of penicillin resistance in clinical isolates of pneumococci. J. Infect. Dis. 159: 1625.
65. Jamin, M.,, C. Damblon,, S. Millier,, R. Hakenbeck, and, J.-M. Frère. 1993. Penicillin-binding protein 2x of Streptococcus pneumoniae: enzymic activities and interactions with beta-lactams. Biochem. J. 292: 735741.
66. Jensen, M. S.,, C. Yang,, Y. Hsiao,, N. Rivera,, K. M. Wells,, J. Y. L. Chung,, N. Yasuda,, D. L. Hughes, and, P. J. Reider. 2000. Synthesis of an anti-methicillin-resistant Staphylococcus aureus (MRSA) carbapenem via stannatrane-mediated Stille coupling. Org. Lett. 2: 10811084.
67. Kano, Y.,, T. Maruyama,, Y. Sambongi,, K. Aihara,, K. Atsumi,, K. Iwamatsu, and, T. Ida. 2001. Preparation of novel carbapenem derivatives as antimicrobial agents. PCT Int. Appl. Patent no. WO 2001055154.
68. Karibian, D., and, G. Starka. 1987. The penicillin-binding proteins of Zymomonas mobilis Zm4. FEMS Microbiol. Lett. 41: 121125.
69. Katayama, Y.,, H.-Z. Zhang, and, H. F. Chambers. 2004. PBP 2a mutations producing very-high-level resistance to beta-lactams. Antimicrob. Agents Chemother. 48: 453459.
70. Kawahata, Y.,, S. Tomida,, T. Nishino, and, T. Tanino. 1983. Studies on antibacterial activity of β-lactam antibiotics against Acinetobacter calcoaceticus. In K. H. Spitzy and, K. Karrer (ed.), Proceedings of the 13th International Congress of Chemotherapy. 2 88/58–88/62. Verlag H. Egermann, Vienna, Austria.
71. Kawamoto, I.,, Y. Shimoji,, O. Kanno,, K. Kojima,, K. Ishi-kawa,, E. Matsuyama,, Y. Ashida,, T. Shibayama,, T. Fuku-oka, and, S. Ohya. 2003. Synthesis and structure-activity relationships of novel parenteral carbapenems, CS-023 (R-115685) and related compounds containing an amidine moiety. J. Antibiot. 56: 565579.
72. Kristiansen, M. M.,, C. Leandro,, D. Ordway,, M. Martins,, M. Viveiros,, T. Pacheco,, J. E. Kristiansen, and, L. Amaral. 2003. Phenothiazines alter resistance of methicillin-resistant strains of Staphylococcus aureus (MRSA) to oxacillin in vitro. Int. J. Antimicrob. Agents 22: 250253.
73. Kubo, I.,, K. Nihei, and, K. Tsujimoto. 2003. Antibacterial action of anacardic acids against methicillin resistant Staphylococcus aureus (MRSA). J. Agric. Food Chem. 51: 76247628.
74. Kwon, D. H.,, M. P. Dore,, J. J. Kim,, M. Kato,, M. Lee,, J. Y. Wu, and, D. Y. Graham. 2003. High-level β-lactam resistance associated with acquired multidrug resistance in Helicobacter pylori. Antimicrob. Agents Chemother. 47: 21692178.
75. Lepage, S.,, P. Dubois,, T. K. Ghosh,, B. Joris,, S. Mahapatra,, M. Kundu,, J. Basu,, P. Chakrabarti,, S. T. Cole,, M. Nguyen-Disteche, and, J.-M. Ghuysen. 1997. Dual multimodular class A penicillin-binding proteins in Mycobacterium leprae. J. Bacteriol. 179: 46274630.
76. Liao, X., and, R. E. Hancock. 1997. Identification of a penicillin-binding protein 3 homolog, PBP3x, in Pseudomonas aeruginosa: gene cloning and growth phase-dependent expression. J. Bacteriol. 179: 14901496.
77. Liao, X., and, R. E. W. Hancock. 1997. Susceptibility to β-lactam antibiotics of Pseudomonas aeruginosa overproducing penicillin-binding protein 3. Antimicrob. Agents Chemother. 41: 11581161.
78. Ligozzi, M.,, F. Pittaluga, and, R. Fontana. 1996. Modification of penicillin-binding protein 5 associated with high-level ampicillin resistance in Enterococcus faecium. Antimi-crob. Agents Chemother. 40: 354357.
79. Lim, D., and, N. C. J. Strynadka. 2002. Structural basis for the b lactam resistance of PBP2a from methicillin-resistant Staphylococcus aureus. Nat. Struct. Biol. 9: 870876.
80. Liu, I. X.,, D. G. Durham, and, R. M. E. Richards. 2000. Baicalin synergy with β-lactam antibiotics against methicil-lin-resistant Staphylococcus aureus and other β-lactam-resistant strains of S. aureus. J. Pharm. Pharmacol. 52: 361366.
81. Livermore, D. M. 1987. Radiolabeling of penicillin-binding proteins (PBPs) in intact Pseudomonas aeruginosa cells: consequences of β-lactamase activity by PBP-5. J. Antimi-crob. Chemother. 19: 733742.
82. Lovering, A. L.,, L. De Castro,, D. Lim, and, N. C. J. Strynadka. 2006. Structural analysis of an “open” form of PBP1B from Streptococcus pneumoniae. Protein Sci. 15: 17011709.
83. Lu, W.-P.,, E. Kincaid,, Y. Sun, and, M. D. Bauer. 2001. Kinetics of β-lactam interactions with penicillin-susceptible and -resistant penicillin-binding protein 2x proteins from Streptococcus pneumoniae: involvement of acylation and deacylation in β-lactam resistance. J. Biol. Chem. 276: 3149431501.
84. 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 β-lactams using electrospray mass spectrometry. Biochemistry 38: 65376546.
85. Lujan, R.,, J. A. Saez-Nieto,, J. V. Martinez-Suarez,, B. G. Spratt,, L. Bowler, and, Q. Y. Zhang. 1991. Nucleotide sequences and genetic diversity of the penA genes from penicillin sensitive and moderately penicillin resistant strains of Neisseria lactamica, p. 9398. In M. Achtman (ed.), Neisseriae 1990, Proceedings of the 7th International Pathogenic Neisseria Conference 1990. Walter de Gruyter, Berlin, Germany.
86. Lujan, R.,, Q. Y. Zhang,, J. A. Saez Nieto,, D. M. Jones, and, B. G. Spratt. 1991. Penicillin-resistant isolates of Neisseria lactamica produce altered forms of penicillin-binding protein 2 that arose by interspecies horizontal gene transfer. Antimicrob. Agents Chemother. 35: 300304.
87. MacKenzie, C. R.,, I. J. McDonald, and, K. G. Johnson. 1980. Antibiotic resistance in Neisseria denitrificans. Antimicrob. Agents Chemother. 17: 789797.
88. Maggs, A. F.,, J. M. J. Logan,, P. E. Carter, and, T. H. Pennington. 1998. The detection of penicillin insensitivity in Neisseria meningitidis by polymerase chain reaction. J. Antimicrob. Chemother. 42: 303307.
89. Mahapatra, S.,, S. Bhakta,, J. Ahamed, and, J. Basu. 2000. Characterization of derivatives of the high-Mol.-mass penicillin-binding protein (PBP) 1 of Mycobacterium leprae. Biochem. J. 350: 7580.
90. Macheboeuf, P.,, A. M. Di Guilmi,, V. Job,, T. Vernet,, O. Dideberg, and, A. Dessen. 2005. Active site restructuring regulates ligand recognition in class A penicillin-binding proteins. Proc. Natl. Acad. Sci. USA 102: 577582.
91. Masson, J. M.,, A. Kazmierczak, and, R. Labia. 1983. Interactions of clavulanic acid and sulbactam with penicillin-binding proteins. Drugs Exp. Clin. Res. 9: 513518.
92. Mendelman, P. M.,, J. Campos,, D. O. Chaffin,, D. A. Serfass,, A. L. Smith, and, J. A. Saez-Nieto. 1988. Relative penicillin G resistance in Neisseria meningitidis and reduced affinity of penicillin-binding protein 3. Antimicrob. Agents Che-mother. 32: 706709.
93. Mendelman, P. M.,, D. O. Chaffin, and, G. Kalaitzoglou. 1990. Penicillin-binding proteins and ampicillin resistance in Haemophilus influenzae. J. Antimicrob. Chemother. 25: 525534.
94. Mirelman, D.,, Y. Nuchamowitz, and, E. Rubinstein. 1981. Insensitivity of peptidoglycan biosynthetic reactions to β-lactam antibiotics in a clinical isolate of Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 19: 687695.
95. Moreira, B.,, S. Boyle-Vavra,, B. L. M. Dejonge, and, R. S. Daum. 1997. Increased production of penicillin-binding protein 2, increased detection of other penicillin-binding proteins, and decreased coagulase activity associated with glycopeptide resistance in Staphylococcus aureus. Antimi-crob. Agents Chemother. 41: 17881793.
96. Mouz, N.,, A. M. Di Guilmi,, E. Gordon,, R. Hakenbecki,, O. Dideberg, and, T. Vernet. 1999. Mutations in the active site of penicillin-binding protein PBP2x from Streptococcus pneumoniae. Role in the specificity for β-lactam antibiotics. J. Biol. Chem. 274: 1917519180.
97. Murakami, K.,, K. Nomura,, M. Doi, and, T. Yoshida. 1987. Production of low-affinity penicillin-binding protein by low- and high-resistance groups of methicillin-resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 31: 13071311.
98. Muroi, H., and, I. Kubo. 1996. Antibacterial activity of anacardic acid and totarol, alone and in combination with methicillin, against methicillin-resistant Staphylococcus aureus. J. Appl. Bacteriol. 80: 387394.
99. Nagai, K.,, T. A. Davies,, M. R. Jacobs, and, P. C. Appel-baum. 2002. Effects of amino acid alterations in penicillin-binding proteins (PBPs) 1a, 2b, and 2x on PBP affinities of penicillin, ampicillin, amoxicillin, cefditoren, cefuroxime, cefprozil, and cefaclor in 18 clinical isolates of penicillin-susceptible, -intermediate, and -resistant pneumococci. Antimicrob. Agents Chemother. 46: 12731280.
100. Nakayama, A., and, A. Takao. 2003. Beta-lactam resistance in Streptococcus mitis isolated from saliva of healthy subjects. J. Infect. Chemother. 9: 321327.
101. Neuwirth, C.,, E. Siebor,, J.-M. Duez,, A. Pechinot, and, A. Kazmierczak. 1995. Imipenem resistance in clinical isolates of Proteus mirabilis associated with alterations in penicillin-binding proteins. J. Antimicrob. Chemother. 36: 335342.
102. Obara, M., and, T. Nakae. 1991. Mechanisms of resistance to β-lactam antibiotics in Acinetobacter calcoaceticus. J. Antimicrob. Chemother. 28: 791800.
103. Okada, M. 1991. Resistance mechanisms of Campylobacter to β-lactam antibiotics. Hiroshima Daigaku Shigaku Zasshi 23: 1830.
104. Okamoto, T.,, H. Yoshiyama,, T. Nakazawa,, I.-D. Park,, M.-W. Chang,, H. Yanai,, K. Okita, and, M. Shirai. 2002. A change in PBP1 is involved in amoxicillin resistance of clinical isolates of Helicobacter pylori. J. Antimicrob. Chemother. 50: 849856.
105. Orus, P., and, M. Vinas. 2000. Transfer of penicillin resistance between Neisseriae in microcosm. Microb. Drug Res. 6: 99104.
106. Orus, P., and, M. Vinas. 2001. Mechanisms other than penicillin-binding protein-2 alterations may contribute to moderate penicillin resistance in Neisseria meningitidis. Int. J. Antimicrob. Agents 18: 113119.
107. Pagani, L.,, M. Debiaggi,, R. Tenni,, P. M. Cereda,, P. Lan-dini, and, E. Romero. 1988. β-Lactam resistant Pseudomonas aeruginosa strains emerging during therapy: synergistic resistance mechanisms. Microbiologica 11: 4753.
108. Page, M. G. P. 1994. The reaction of cephalosporins with penicillin-binding protein 1bg from Escherichia coli. Biochim. Biophys. Acta 1205: 199206.
109. Page, M. G. P. 2004. Cephalosporins in development. Expert Opin. Investig. Drugs 13: 973985.
110. Page, M. G. P. 2006. Anti-MRSA β-lactams in development. Curr. Opin. Pharmacol. 6: 480485.
111. Page, M.,, D. Bur,, F. Danel,, I. Heinze-Krauss,, M. Kania,, B. Mensch,, V. Runtz,, U. Weiss, and, F. Winkler. 1998. Inhibition of the penicillin-binding proteins of methicillin-resistant staphylococci by pyrrolidinone-3-ylidenemethyl cephems, Poster F-022. Presented at the 38th ICAAC Intersic. Conf. Antimicrob. Agents Chemother.
112. Pares, S.,, N. Mouz,, Y. Petillot,, R. Hakenbeck, and, O. Dide-berg. 1996. X-ray structure of Streptococcus pneumoniae PBP2x, a primary penicillin target enzyme. Nat. Struct. Biol. 3: 284289.
113. Perez-Castillo, A.,, A. M. Perez-Castillo, and, J. A. Saez-Nieto. 1994. Sequence of the penicillin-binding protein 2-encoding gene (penA) of Neisseria perflava/sicca. Gene 146: 9193.
114. Pierre, J.,, A. Boisivon, and, L. Gutmann. 1990. Alteration of PBP 3 entails resistance to imipenem in Listeria monocyto-genes. Antimicrob. Agents Chemother. 34: 16951698.
115. Piras, G.,, A. El Kharroubi,, J. Van Beeumen,, E. Coeme,, J. Coyette, and, J.-M. Ghuysen, 1990. Characterization of an Enterococcus hirae penicillin-binding protein 3 with low penicillin affinity. J. Bacteriol. 172: 68566862.
116. Rice, L. B.,, S. Bellais,, L. L. Carias,, R. Hutton-Thomas,, R. A. Bonomo,, P. Caspers,, M. G. Page, and, L. Gutmann. 2004. Impact of specific pbp5 mutations on expression of β-lactam resistance in Enterococcus faecium. Antimicrob. Agents Chemother. 48: 30283032.
117. Rodriguez-Tebar, A.,, F. Rojo,, D. Damaso, and, D. Vazquez. 1982. Carbenicillin resistance of Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 22: 255261.
118. Ropp, P. A.,, M. Hu,, M. Olesky, and, R. A. Nicholas. 2002. Mutations in ponA, the gene encoding penicillin-binding protein 1, and a novel locus, penC, are required for high-level chromosomally mediated penicillin resistance in Neisseria gonorrhoeae. Antimicrob. Agents Chemother. 46: 769777.
119. Ropp, P. A., and, R. A. Nicholas. 1997. Cloning and characterization of the ponA gene encoding penicillin-binding protein 1 from Neisseria gonorrhoeae and Neisseria meningiti-dis. J. Bacteriol. 179: 27832787.
120. Roychoudhury, S.,, R. E. Kaiser,, D. N. Brems, and, W.-K. Yeh. 1996. Specific interaction between β-lactams and soluble penicillin-binding protein 2a from methicillin-resistant Staphylococcus aureus: development of a chromogenic assay. Antimicrob. Agents Chemother. 40: 20752079.
121. Rybkine, T.,, J.-L. Mainardi,, W. Sougakoff,, E. Collatz, and, L. Gutmann. 1998. Penicillin-binding protein 5 sequence alterations in clinical isolates of Enterococcus faecium with different levels of β-lactam resistance. J. Infect. Dis. 178: 159163.
122. Sato, Y.,, H. Shibata,, T. Arai,, A. Yamamoto,, Y. Okimura,, N. Arakaki, and, T. Higuti. 2004. Variation in synergistic activity by flavone and its related compounds on the increased susceptibility of various strains of methicillin-resistant Staphylococcus aureus to β-lactam antibiotics. Int. J. Antimicrob. Agents 24: 226233.
123. Satta, G.,, P. Canepari,, R. Maurici,, R. Pompei, and, M. A. Marcialis. 1985. Shifting of the penicillin-binding proteins that are the target for inhibition by β-lactams as a likely mechanism of resistance to antibiotics during therapy. Chemioterapia 4: 113115.
124. 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.
125. Schilf, W., and, H. H. Martin. 1980. Purification of two DD-carboxypeptidases /transpeptidases with different penicillin sensitivities from Proteus mirabilis. Eur. J. Biochem. 105: 361370.
126. Schultz, D. E.,, B. G. Spratt, and, R. A. Nicholas. 1991. Expression and purification of a soluble form of penicillin-binding protein 2 from both penicillin-susceptible and penicillin-resistant Neisseria gonorrhoeae. Protein Expr. Purif. 2: 339349.
127. Sengupta, T. K.,, K. Chaudhuri,, S. Majumdar,, A. Lohia,, A. N. Chatterjee, and, J. Das. 1992. Interaction of Vibrio cholerae cells with β-lactam antibiotics: emergence of resistant cells at a high frequency. Antimicrob. Agents Chemother. 36: 788795.
128. Shiota, S.,, M. Shimizu,, J. Sugiyama,, Y. Morita,, T. Mizushima, and, T. Tsuchiya. 2004. Mechanisms of action of corilagin and tellimagrandin I that remarkably potentiate the activity of β-lactams against methicillin-resistant Staphylococcus aureus. Microbiol. Immunol. 48: 6773.
129. Shirai, M.,, A. Nakazawa,, K. Okita,, K. Okamoto, and, H. Kichiyama. 2004. Mutation in Helicobacter pylori gene pbp1 for amoxicillin resistance and the use of microbial for drug screening. Jpn. Kokai Tokkyo Koho Patent no. JP2004121141.
130. Spratt, B. G. 1988. Hybrid penicillin-binding proteins in penicillin-resistant strains of Neisseria gonorrhoeae. Nature 332: 173176.
131. Spratt, B. G.,, Q. Y. Zhang,, D. M. Jones,, A. Hutchison,, J. A. Brannigan, and, C. G. Dowson. 1989. Recruitment of a penicillin-binding protein gene from Neisseria flavescens during the emergence of penicillin resistance in Neisseria meningitidis. Proc. Natl. Acad. Sci. USA 86: 89888992.
132. Spratt, B. G.,, L. D. Bowler,, Q. Y. Zhang,, J. Zhou, and, J. M. Smith. 1992. Role of interspecies transfer of chromosomal genes in the evolution of penicillin resistance in pathogenic and commensal Neisseria species. J. Mol. Evol. 34: 115125.
133. Srikumar, R.,, E. Tsang, and, K. Poole. 1999. Contribution of the MexAB-OprM multidrug efflux system to the β-lactam resistance of penicillin-binding protein and β-lactamase-derepressed mutants of Pseudomonas aeruginosa. J. Anti-microb. Chemother. 44: 537540.
134. Stapleton, P. D.,, S. Shah,, J. C. Anderson,, Y. Hara,, J. M. T. Hamilton-Miller, and, P. W. Taylor. 2004. Modulation of β-lactam resistance in Staphylococcus aureus by catechins and gallates. Int. J. Antimicrob. Agents 23: 462467.
135. Stapleton, P. D., and, P. W. Taylor. 2002. Methicillin resistance in Staphylococcus aureus: mechanisms and modulation. Sci. Prog. 85: 5772.
136. Stefanelli, P.,, A. Carattoli,, A. Neri,, C. Fazio, and, P. Mastrantonio. 2003. Prediction of decreased susceptibility to penicillin of Neisseria meningitidis strains by real-time PCR. J. Clin. Microbiol. 41: 46664670.
137. Storey, C., and, I. Chopra. 2001. Affinities of β-lactams for penicillin binding proteins of Chlamydia trachomatis and their antichlamydial activities. Antimicrob. Agents Chemother. 45: 303305.
138. Sunagawa, M.,, M. Itoh,, K. Kubota,, A. Sasaki,, Y. Ueda,, P. Angehrn,, A. Bourson,, E. Goetschi,, P. Hebeisen, and, R. L. Then. 2002. New anti-MRSA and anti-VRE carbapenems; synthesis and structure-activity relationships of 1 β-methyl-2-(thiazol-2-ylthio)carbapenems. J. Antibiot. 55: 722757.
139. Tirodimos, I.,, E. Tzelepi, and, V. C. Katsougiannopoulos. 1993. Penicillin-binding protein 2 genes of chromosomally-mediated penicillin-resistant Neisseria gonorrhoeae from Greece: screening for codon Asp-345A. J. Antimicrob. Che-mother. 32: 677684.
140. Tirodimos, I.,, E. Tzelepi,, N. Vavatsi,, K. Delidou, and, J. Doubogias. 1993. Presence of mutation in the penicillin-binding protein 2 (PBP 2) genes of non-β-lactamase producing penicillin-resistant strains of Neisseria gonorrhoeae isolated in Greece. Delt. Hell. Mikrobiol. Hetair. 38: 331341.
141. Toda, M.,, S. Okubo,, Y. Hara, and, T. Shimamura. 1991. Antibacterial and bactericidal activities of tea extracts and catechins against methicillin resistant Staphylococcus aureus. Nippon Saikingaku Zasshi. 46: 839845.
142. Tokue, Y.,, S. Shoji,, K. Satoh,, A. Watanabe, and, M. Mot-omiya. 1992. Comparison of a polymerase chain reaction assay and a conventional microbiologic method for detection of methicillin-resistant Staphylococcus aureus. Antimi-crob. Agents Chemother. 36: 69.
143. Tsushima, M.,, K. Iwamatsu,, A. Tamura, and, S. Shibahara. 1998. Novel cephalosporin derivatives possessing a bicyclic heterocycle at the 3-position. I. Synthesis and biological activities of 3-(benzothiazol-2-yl)thiocephalosporin derivatives, CP0467 and related compounds. Bioorg. Med. Chem. 6: 10091017.
144. Ubukata, K.,, N. Chiba,, N. Nakayama, and, M. Konno. 1999. Drug-resistance mechanism of β-lactamase nonproducing ampicillin-resistant strains of Haemophilus influen-zae. Nippon Rinsho Biseibutsugaku Zasshi 9: 2229.
145. Ubukata, K.,, Y. Shibasaki,, K. Yamamoto,, N. Chiba,, K. Hasegawa,, Y. Takeuchi,, K. Sunakawa,, M. Inoue, and, M. Konno. 2001. Association of amino acid substitutions in penicillin-binding protein 3 with beta-lactam resistance in beta-lactamase-negative ampicillin-resistant Haemophilus influenzae. Antimicrob. Agents Chemother. 45: 16931699.
146. Urban, C.,, E. Go,, N. Mariano, and, J. J. Rahal. 1995. Interaction of sulbactam, clavulanic acid and tazobactam with penicillin-binding proteins of imipenem-resistant and -susceptible Acinetobacter baumannii. FEMS Microbiol. Lett. 125: 193198.
147. Utsui, Y.,, M. Tajima,, R. Sekiguchi,, E. Suzuki, and, T. Yokota. 1983. Role of an altered penicillin-binding protein (PBP) and membrane-bound penicillinase in cephem-resistant Staphylococcus aureus. In K. H. Spitzy and K. Karrer (ed.), Proceedings of the 13th International Congress of Chemotherapy. Verlag H. Egermann, Vienna, Austria.
148. Vicente, M. F.,, J. Berenguer,, M. A. De Pedro,, J. C. Perez-Diaz, and, F. Baquero. 1990. Penicillin-binding proteins in Listeria monocytogenes. Acta Microbiol. Hung. 37: 227231.
149. Vicente, M. F.,, J. C. Perez-Diaz,, F. Baquero,, M. A. De Pedro, and, J. Berenguer. 1990. Penicillin-binding protein 3 of Listeria monocytogenes as the primary lethal target for β-lactams. Antimicrob. Agents Chemother. 34: 539542.
150. Villar, H. E.,, F. Danel, and, D. M. Livermore. 1997. Permeability to carbapenems of Proteus mirabilis mutants selected for resistance to imipenem or other β-lactams. J. Antimi-crob. Chemother. 40: 365370.
151. Vouillamoz, J.,, J. M. Entenza,, P. Hohl, and, P. Moreillon. 2004. LB11058, a new cephalosporin with high penicillin-binding protein 2a affinity and activity in experimental endocarditis due to homogeneously methicillin-resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 48: 43224327.
152. Wexler, H. M., and, S. Halebian. 1990. Alterations to the penicillin-binding proteins in the Bacteroides fragilis group: a mechanism for non-β-lactamase mediated cefoxitin resistance. J. Antimicrob. Chemother. 26: 720.
153. Yamazaki, H.,, Y. Tsuchida,, H. Satoh,, S. Kawashima,, H. Hanaki, and, K. Hiramatsu. 2000. Novel cephalosporins 2. Synthesis of 3-heterocyclic-fused thiopyranylthiovinyl ceph-alosporins and antibacterial activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis. J. Antibiot. 53: 551555.
154. Yoshizawa, H.,, H. Itani,, K. Ishikura,, T. Irie,, K. Yokoo,, T. Kubota,, K. Minami,, T. Iwaki,, H. Miwa, and, Y. Nishitani. 2002. S-3578, a new broad spectrum parenteral cephalo-sporin exhibiting potent activity against both methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. Synthesis and structure-activity relationships. J. Antibiot. 55: 975992.
155. Yotsuji, A.,, J. Mitsuyama,, R. Hori,, T. Yasuda,, I. Saikawa,, M. Inoue, and, S. Mitsuhashi. 1988. Mechanism of action of cephalosporins and resistance caused by decreased affinity for penicillin-binding proteins in Bacteroides fragilis. Anti-microb. Agents Chemother. 32: 18481853.
156. Zhang, F.-K.,, M. G. P. Page, and, S.-H. Jin. 2000. Factors determining the resistance of Pseudomonas aeruginosa to β-lactam antibiotics. Zhongguo Kang Sheng Su Za Zhi 25: 362367.
157. Zhang, Q. Y.,, D. M. Jones,, J. A. Saez Nieto,, E. P. Trallero, and, B. G. Spratt. 1990. Genetic diversity of penicillin-binding protein 2 genes of penicillin-resistant strains of Neisseria meningitidis revealed by fingerprinting of amplified DNA. Antimicrob. Agents Chemother 34: 15231528.
158. Zorzi, W.,, X. Y. Zhou,, O. Dardenne,, J. Lamotte,, D. Raze,, J. Pierre,, L. Gutmann, and, J. Coyette. 1996. Structure of the low-affinity penicillin-binding protein 5 PBP5fm in wild-type and highly penicillin-resistant strains of Enterococcus faecium. J. Bacteriol. 178: 49484957.


Generic image for table
Table 7.1

Comparison of the PBPs in , and

Citation: Page M. 2007. Resistance Mediated by Penicillin-Binding Proteins, p 81-99. In Bonomo R, Tolmasky M (ed), Enzyme-Mediated Resistance to Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555815615.ch7
Generic image for table
Table 7.2

Comparison of susceptibilities of the PBPs of and to different β-lactam classes

Citation: Page M. 2007. Resistance Mediated by Penicillin-Binding Proteins, p 81-99. In Bonomo R, Tolmasky M (ed), Enzyme-Mediated Resistance to Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555815615.ch7
Generic image for table
Table 7.3

Distribution of PBP types among the bacteria and their contribution to β-lactam resistance

Citation: Page M. 2007. Resistance Mediated by Penicillin-Binding Proteins, p 81-99. In Bonomo R, Tolmasky M (ed), Enzyme-Mediated Resistance to Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555815615.ch7
Generic image for table
Table 7.4

Kinetic parameters describing the reaction of soluble constructs of PBPs

Citation: Page M. 2007. Resistance Mediated by Penicillin-Binding Proteins, p 81-99. In Bonomo R, Tolmasky M (ed), Enzyme-Mediated Resistance to Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555815615.ch7
Generic image for table
Table 7.5

Representative anti-MRSA cephalosporins

Citation: Page M. 2007. Resistance Mediated by Penicillin-Binding Proteins, p 81-99. In Bonomo R, Tolmasky M (ed), Enzyme-Mediated Resistance to Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555815615.ch7
Generic image for table
Table 7.6

Anti-MRSA carbapenems

Citation: Page M. 2007. Resistance Mediated by Penicillin-Binding Proteins, p 81-99. In Bonomo R, Tolmasky M (ed), Enzyme-Mediated Resistance to Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555815615.ch7
Generic image for table
Table 7.7

Modulators of PBP2′-mediated resistance in staphylococci

Citation: Page M. 2007. Resistance Mediated by Penicillin-Binding Proteins, p 81-99. In Bonomo R, Tolmasky M (ed), Enzyme-Mediated Resistance to Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555815615.ch7

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error