This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vakulenko, S. B. Articles by Lerner, S. A. Search for Related Content PubMed PubMed Citation Articles by Vakulenko, S. B. Articles by Lerner, S. A.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, Aug 1995, 1878-1880, Vol 39, No. 8
Copyright © 1995 by the American Society for Microbiology. All rights reserved.

Effects of Asp-179 mutations in TEMpUC19 beta-lactamase on susceptibility to beta-lactams

SB Vakulenko, M Toth, P Taibi, S Mobashery and SA Lerner
Department of Medicine, Wayne State University, Detroit, Michigan 48202, USA.

To examine the effect of disruption of the salt bridge (between Arg-164 and Asp-179 [numbering of Ambler et al. (Biochem J. 267:269-272, 1991)]) that anchors the conserved omega-loop in class A beta- lactamases, we obtained mutant enzymes with each of the 19 other amino acid residues replacing Asp-179 in the TEM beta-lactamase encoded by pUC19 and studied the level of resistance to various beta-lactams conferred by each enzyme. All mutations of Asp-179 compromised the level of resistance to ampicillin, but most of them enhanced resistance to ceftazidime. In contrast, mutations of Asp-179 generally impaired the low levels of resistance to cefepime and aztreonam. One might expect to find clinical isolates with mutant TEM beta-lactamases with replacements of Asp-179 that express an expanded spectrum of resistance to beta-lactams including ceftazidime.

This article has been cited by other articles:

• Bos, F., Pleiss, J. (2008). Conserved Water Molecules Stabilize the {Omega}-Loop in Class A {beta}-Lactamases. Antimicrob. Agents Chemother. 52: 1072-1079 [Abstract] [Full Text]  
• Delmas, J., Robin, F., Bittar, F., Chanal, C., Bonnet, R. (2005). Unexpected Enzyme TEM-126: Role of Mutation Asp179Glu. Antimicrob. Agents Chemother. 49: 4280-4287 [Abstract] [Full Text]  
• Ma, L., Alba, J., Chang, F.-Y., Ishiguro, M., Yamaguchi, K., Siu, L. K., Ishii, Y. (2005). Novel SHV-Derived Extended-Spectrum {beta}-Lactamase, SHV-57, That Confers Resistance to Ceftazidime but Not Cefazolin. Antimicrob. Agents Chemother. 49: 600-605 [Abstract] [Full Text]  
• Fujii, R., Kitaoka, M., Hayashi, K. (2004). One-step random mutagenesis by error-prone rolling circle amplification. Nucleic Acids Res 32: e145-e145 [Abstract] [Full Text]  
• Majiduddin, F. K., Palzkill, T. (2003). An Analysis of Why Highly Similar Enzymes Evolve Differently. Genetics 163: 457-466 [Abstract] [Full Text]  
• Bradford, P. A. (2001). Extended-Spectrum {beta}-Lactamases in the 21st Century: Characterization, Epidemiology, and Detection of This Important Resistance Threat. Clin. Microbiol. Rev. 14: 933-951 [Abstract] [Full Text]  
• Vakulenko, S. B., Taibi-Tronche, P., Toth, M., Massova, I., Lerner, S. A., Mobashery, S. (1999). Effects on Substrate Profile by Mutational Substitutions at Positions 164 and 179 of the Class A TEMpUC19 beta -Lactamase from Escherichia coli. J. Biol. Chem. 274: 23052-23060 [Abstract] [Full Text]  
• Therrien, C., Sanschagrin, F., Palzkill, T., Levesque, R. C. (1998). Roles of Amino Acids 161 to 179 in the PSE-4 Omega  Loop in Substrate Specificity and in Resistance to Ceftazidime. Antimicrob. Agents Chemother. 42: 2576-2583 [Abstract] [Full Text]  
• Tranier, S., Bouthors, A.-T., Maveyraud, L., Guillet, V., Sougakoff, W., Samama, J.-P. (2000). The High Resolution Crystal Structure for Class A beta -Lactamase PER-1 Reveals the Bases for Its Increase in Breadth of Activity. J. Biol. Chem. 275: 28075-28082 [Abstract] [Full Text]