Integron carrying a novel metallo-beta-lactamase gene, bla(IMP-16), and a fused form of aminoglycoside-resistant gene aac(6')-30/aac(6')-Ib': Report from the SENTRY antimicrobial surveillance program
Mendes, Rodrigo Elisandro [UNIFESP]
Toleman, Mark A.
Sader, Helio Silva [UNIFESP]
Jones, Ronald N.
Walsh, Timothy R.
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Since January 2002 Pseudomonas sp. strains resistant to carbapenems and ceftazidime have been routinely screened as part of the SENTRY Antimicrobial Surveillance Program for metallo-beta-lactamase production, and their resistance determinants have been analyzed. Pseudomonas aeruginosa index strain 101-4704, which harbors a novel bla(IMP) variant, bla(IMP-16), was isolated in April 2002 from a 60-year-old man in Brasilia, Brazil. bla(IMP-16) was found on the chromosome of the P. aeruginosa index strain, and the deduced amino acid sequence (IMP-16) showed the greatest identities to IMP-11 (90.3%) and IMP-8 (89.5%). Sequence analysis revealed that blaIMP-16 was associated with a class 1 integron, which also encoded aminoglycoside-modifying enzymes. Downstream of bla(IMP-16) resided an open reading frame, which consisted of a new aminoglycoside-modifying gene, namely, aac(6')-30, which was fused with aac(6')-Ib'. the amino acid sequence of the aac(6')-30 putative protein showed the most identity (52.7%) to the sequence of AAC(6')-29b described previously. the fourth gene cassette constituted aadA1. the steady-state kinetics of IMP-16 demonstrated that the enzyme preferred cephalosporins and carbapenems to penicillins. the main functional difference observed among the kinetic values for IMP-16 compared to those for other IMPs was a lack of cefoxitin hydrolysis and a lower k(cat)/K-m value for imipenem (0.36 muM(-1) (.) s(-1)). This report further emphasizes the spread of metallo-beta-lactamase genes and their close association with various aminoglycoside resistance genes.
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