Affiliation:
1. Dipartimento di Biologia Molecolare, Sezione di Microbiologia, Università di Siena, I-53100-Siena,1
2. Dipartimento di Scienze e Tecnologie Biomediche, Università di L'Aquila, I-67100-L'Aquila,2 and
3. Dipartimento di Patologia, Sezione di Microbiologia, Università di Verona, I-37134-Verona,3 Italy
Abstract
ABSTRACT
The metallo-β-lactamase determinant of
Acinetobacter baumannii
AC-54/97, a clinical isolate from Italy that was previously shown to produce an enzyme related to IMP-1, was isolated by means of a PCR methodology which targets amplification of gene cassette arrays inserted into class 1 integrons. Sequencing revealed that this determinant was an allelic variant (named
bla
IMP-2
) of
bla
IMP
found in Japanese isolates and that it was divergent from the latter by 12% of its nucleotide sequence, which evidently had been acquired independently. Similar to
bla
IMP
,
bla
IMP-2
was also carried by an integron-borne gene cassette. However, the 59-base element of the
bla
IMP-2
cassette was unrelated to those of the
bla
IMP
cassettes found in Japanese isolates, indicating a different phylogeny for the gene cassettes carrying the two allelic variants. Expression of the integron-borne
bla
IMP-2
gene in
Escherichia coli
resulted in a significant decrease in susceptibility to a broad array of β-lactams (ampicillin, carbenicillin, cephalothin, cefoxitin, ceftazidime, cefepime, and carbapenems). The IMP-2 enzyme was purified from an
Escherichia coli
strain carrying the cloned determinant, and kinetic parameters were determined with several β-lactam substrates. Compared to IMP-1, the kinetic parameters of IMP-2 were similar overall with some β-lactam substrates (cefoxitin, ceftazidime, cefepime, and imipenem) but remarkably different with others (ampicillin, carbenicillin, cephaloridine, and meropenem), revealing a functional significance of at least some of the mutations that differentiate the two IMP variants. Present findings suggest that the environmental reservoir of
bla
IMP
alleles could be widespread and raise a question about the global risk of their transfer to clinically relevant species.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
220 articles.
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