[en] ABSTRACT Over the last two decades, antimicrobial resistance has become a global
health problem. In Gram-negative bacteria, metallo-b-lactamases (MBLs), which inactivate
virtually all b-lactams, increasingly contribute to this phenomenon. The aim of this
study is to characterize VIM-52, a His224Arg variant of VIM-1, identified in a Klebsiella
pneumoniae clinical isolate. VIM-52 conferred lower MICs to cefepime and ceftazidime
compared to VIM-1. These results were confirmed by steady-state kinetic measurements,
where VIM-52 yielded a lower activity toward ceftazidime and cefepime but not against
carbapenems. Residue 224 is part of the L10 loop (residues 221 to 241), which borders
the active site. As Arg 224 and Ser 228 both play an important and interrelated role in
enzymatic activity, stability, and substrate specificity for the MBLs, targeted mutagenesis
at both positions was performed and further confirmed their crucial role for substrate
specificity.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
de Barsy, Marie
Mercuri, Paola ; Université de Liège - ULiège > Département des sciences de la vie > Macromolécules biologiques
Oueslati, Saoussen
Elisée, Eddy
Huang, Te-Din
Sacré, Pierre
Iorga, Bogdan I
Naas, Thierry
Galleni, Moreno ; Université de Liège - ULiège > Département des sciences de la vie > Macromolécules biologiques
Bogaerts, Pierre
Language :
English
Title :
Detection and Characterization of VIM-52, a New Variant of VIM-1 from a Klebsiella pneumoniae Clinical Isolate
Publication date :
18 October 2021
Journal title :
Antimicrobial Agents and Chemotherapy
ISSN :
0066-4804
eISSN :
1098-6596
Publisher :
American Society for Microbiology, United States - District of Columbia
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