Characterization of a new TEM-derived beta-lactamase produced in a Serratia marcescens strain.
A natural TEM variant beta-lactamase was isolated from an epidemic strain of Serratia marcescens. Nucleotide gene sequencing revealed multiple point mutations located in the 42-to-44 tripeptide and positions 145 to 146, 178, and 238. In addition, a glutamic acid 212 deletion was also found. The purified enzyme was studied from a kinetic point of view, revealing the highest catalytic efficiency (k[cat]/Km) values for ceftazidime and aztreonam compared with the TEM-1 prototype enzyme. The in vitro resistance correlated with kinetic parameters, and the enzyme also mediated resistance to some penicillins and an ampicillin-clavulanic acid combination. The mutational and kinetic changes are discussed in relation to the three-dimensional crystallographic structure of the wild-type TEM-1 enzyme.
Perilli
M
M
Dipartimento di Scienze e Tecnologie Biomediche, Cattedra di Chimica Biologica, Facoltà di Medicina e Chirurgia, Università degli Studi dell'Aquila, L'Aquila, Italy.
Felici
A
A
Franceschini
N
N
De Santis
A
A
Pagani
L
L
Luzzaro
F
F
Oratore
A
A
Rossolini
G M
GM
Knox
J R
JR
Amicosante
G
G
D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D003461:Crystallography; D004352:Drug Resistance, Microbial; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010406:Penicillins / Q000494:pharmacology; D012706:Serratia marcescens / Q000201:enzymology*; D001618:beta-Lactamases / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism
D010406:Penicillins; D001618:beta-Lactamases; C034413:beta-lactamase TEM-1