Affiliation:
1. Servicio de Microbiología
2. Unidad de Secuenciación, Hospital Son Dureta, Palma de Mallorca, Spain
Abstract
ABSTRACT
The molecular mechanisms of β-lactam resistance mediated by AmpC hyperproduction in natural strains of
Pseudomonas aeruginosa
were investigated in a collection of 10 isogenic, ceftazidime-susceptible and -resistant pairs of isolates, each sequentially recovered from a different intensive care unit patient treated with β-lactams. All 10 ceftazidime-resistant mutants hyperproduced AmpC (β-lactamase activities were 12- to 657-fold higher than those of the parent strains), but none of them harbored mutations in
ampR
or the
ampC-ampR
intergenic region. On the other hand, six of them harbored inactivating mutations in
ampD
: four contained frameshift mutations, one had a C→T mutation, creating a premature stop codon, and finally, one had a large deletion, including the complete
ampDE
region. Complementation studies revealed that only three of the six
ampD
mutants could be fully transcomplemented with either
ampD
- or
ampDE
-harboring plasmids, whereas one of them could be transcomplemented only with
ampDE
and two of them (including the mutant with the deletion of the
ampDE
region and one with an
ampD
frameshift mutation leading to an
ampDE
-fused open reading frame) could not be fully transcomplemented with any of the plasmids. Finally, one of the four mutants with no mutations in
ampD
could be transcomplemented, but only with
ampDE
. Although the inactivation of AmpD is found to be the most frequent mechanism of AmpC hyperproduction in clinical strains, our findings suggest that for certain types of mutations, AmpE plays an indirect role in resistance and that there are other unknown genes involved in AmpC hyperproduction, with at least one of them apparently located close to the
ampDE
operon.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
143 articles.
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