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  • Title: Effects of Asp-179 mutations in TEMpUC19 beta-lactamase on susceptibility to beta-lactams.
    Author: Vakulenko SB, Tóth M, Taibi P, Mobashery S, Lerner SA.
    Journal: Antimicrob Agents Chemother; 1995 Aug; 39(8):1878-80. PubMed ID: 7486939.
    Abstract:
    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.
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