This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Nagai, K.
Right arrow Articles by Appelbaum, P. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nagai, K.
Right arrow Articles by Appelbaum, P. C.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, May 2002, p. 1273-1280, Vol. 46, No. 5
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.5.1273-1280.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

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

Kensuke Nagai,1 Todd A. Davies,1 Michael R. Jacobs,2 and Peter C. Appelbaum1*

Department of Pathology, Hershey Medical Center, Hershey, Pennsylvania,1 Department of Pathology, Case Western Reserve University, Cleveland, Ohio2

Received 15 October 2001/ Returned for modification 7 January 2002/ Accepted 24 January 2002

Amino acid alterations in or flanking conserved motifs making up the active binding sites of penicillin-binding proteins (PBPs) 1a, 2b, and 2x of pneumococci were correlated with changes in affinities of penicillin, ampicillin, amoxicillin, cefditoren, cefuroxime, cefprozil, and cefaclor for these PBPs. Four penicillin-susceptible (PSSP), eight penicillin-intermediate (PISP), and six penicillin-resistant (PRSP) pneumococci were studied by DNA sequencing of the penicillin-binding sites of the pbp1a, -2x, and -2b genes of strains and by determining 50% inhibitory concentrations of the seven agents for PBP1a, -2x, and -2b. Two PSSP strains had alterations in PBP2x (L546->V) (one strain) or PBP2b (T445->A) (one strain). All eight PISP strains had at least two alterations--T338->P or A or H394->Y in PBP2X and T445->A in BPB2b. All PRSP strains had the same changes seen in PISP strains, as well as T371->A or S substitutions in PBP1a. The two most resistant PRSP strains had a second change in PBP2x (M339->F) in a conserved motif. The affinities of penicillin and ampicillin for all three PBPs were decreased for PRSP and most PISP strains. The affinity of amoxicillin for PBP1a and -2x was decreased only for PRSP. Cefaclor and cefprozil showed decreased affinity of PRSP but not PISP for all three PBPs. Cefuroxime showed decreased affinity of PISP and PRSP for PBP1a and -2x but no change for PBP2b. Cefditoren showed no difference in PBP affinity based on penicillin or cefditoren MICs, indicating a different PBP target for this agent. Overall, the MICs for and PBP affinities of the strains correlated with the changes found in the PBP active binding sites.

* Corresponding author. Mailing address: 500 University Dr., Hershey, PA 17033. Phone: (717) 531-5113. Fax: (717) 531-7953. E-mail: pappelbaum{at}psu.edu.

Antimicrobial Agents and Chemotherapy, May 2002, p. 1273-1280, Vol. 46, No. 5
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.5.1273-1280.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Kosowska-Shick, K., McGhee, P., Appelbaum, P. C. (2009). Binding of Faropenem and Other {beta}-Lactam Agents to Penicillin-Binding Proteins of Pneumococci with Various {beta}-Lactam Susceptibilities. Antimicrob. Agents Chemother. 53: 2176-2180 [Abstract] [Full Text]  
  • Zerfass, I., Hakenbeck, R., Denapaite, D. (2009). An Important Site in PBP2x of Penicillin-Resistant Clinical Isolates of Streptococcus pneumoniae: Mutational Analysis of Thr338. Antimicrob. Agents Chemother. 53: 1107-1115 [Abstract] [Full Text]  
  • Soriano, F., Cafini, F., Aguilar, L., Tarrago, D., Alou, L., Gimenez, M.-J., Gracia, M., Ponte, M.-C., Leu, D., Pana, M., Letowska, I., Fenoll, A. (2008). Breakthrough in penicillin resistance? Streptococcus pneumoniae isolates with penicillin/cefotaxime MICs of 16 mg/L and their genotypic and geographical relatedness. J Antimicrob Chemother 62: 1234-1240 [Abstract] [Full Text]  
  • Chiu, C.-H., Su, L.-H., Huang, Y.-C., Lai, J.-C., Chen, H.-L., Wu, T.-L., Lin, T.-Y. (2007). Increasing Ceftriaxone Resistance and Multiple Alterations of Penicillin-Binding Proteins among Penicillin-Resistant Streptococcus pneumoniae Isolates in Taiwan. Antimicrob. Agents Chemother. 51: 3404-3406 [Abstract] [Full Text]  
  • Haenni, M., Moreillon, P. (2006). Mutations in Penicillin-Binding Protein (PBP) Genes and in Non-PBP Genes during Selection of Penicillin-Resistant Streptococcus gordonii. Antimicrob. Agents Chemother. 50: 4053-4061 [Abstract] [Full Text]  
  • Davies, T. A., Shang, W., Bush, K. (2006). Activities of Ceftobiprole and Other {beta}-Lactams against Streptococcus pneumoniae Clinical Isolates from the United States with Defined Substitutions in Penicillin-Binding Proteins PBP 1a, PBP 2b, and PBP 2x.. Antimicrob. Agents Chemother. 50: 2530-2532 [Abstract] [Full Text]  
  • Granger, D., Boily-Larouche, G., Turgeon, P., Weiss, K., Roger, M. (2006). Molecular characteristics of pbp1a and pbp2b in clinical Streptococcus pneumoniae isolates in Quebec, Canada. J Antimicrob Chemother 57: 61-70 [Abstract] [Full Text]  
  • Chesnel, L., Carapito, R., Croize, J., Dideberg, O., Vernet, T., Zapun, A. (2005). Identical Penicillin-Binding Domains in Penicillin-Binding Proteins of Streptococcus pneumoniae Clinical Isolates with Different Levels of {beta}-Lactam Resistance. Antimicrob. Agents Chemother. 49: 2895-2902 [Abstract] [Full Text]  
  • Granger, D., Boily-Larouche, G., Turgeon, P., Weiss, K., Roger, M. (2005). Genetic analysis of pbp2x in clinical Streptococcus pneumoniae isolates in Quebec, Canada. J Antimicrob Chemother 55: 832-839 [Abstract] [Full Text]  
  • Kosowska, K., Jacobs, M. R., Bajaksouzian, S., Koeth, L., Appelbaum, P. C. (2004). Alterations of Penicillin-Binding Proteins 1A, 2X, and 2B in Streptococcus pneumoniae Isolates for Which Amoxicillin MICs Are Higher than Penicillin MICs. Antimicrob. Agents Chemother. 48: 4020-4022 [Abstract] [Full Text]  
  • Sanbongi, Y., Ida, T., Ishikawa, M., Osaki, Y., Kataoka, H., Suzuki, T., Kondo, K., Ohsawa, F., Yonezawa, M. (2004). Complete Sequences of Six Penicillin-Binding Protein Genes from 40 Streptococcus pneumoniae Clinical Isolates Collected in Japan. Antimicrob. Agents Chemother. 48: 2244-2250 [Abstract] [Full Text]  
  • Pagliero, E., Chesnel, L., Hopkins, J., Croize, J., Dideberg, O., Vernet, T., Di Guilmi, A. M. (2004). Biochemical Characterization of Streptococcus pneumoniae Penicillin-Binding Protein 2b and Its Implication in {beta}-Lactam Resistance. Antimicrob. Agents Chemother. 48: 1848-1855 [Abstract] [Full Text]  
  • Pernot, L., Chesnel, L., Le Gouellec, A., Croize, J., Vernet, T., Dideberg, O., Dessen, A. (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: 16463-16470 [Abstract] [Full Text]  
  • Chesnel, L., Pernot, L., Lemaire, D., Champelovier, D., Croize, J., Dideberg, O., Vernet, T., Zapun, A. (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: 44448-44456 [Abstract] [Full Text]  
  • Peimbert, M., Segovia, L. (2003). Evolutionary engineering of a {beta}-Lactamase activity on a D-Ala D-Ala transpeptidase fold. Protein Eng Des Sel 16: 27-35 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»