Integron Carrying a Novel Metallo-β-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

• Published in: Antimicrobial agents and chemotherapy Vol. 48; no. 12; pp. 4693 - 4702
• Main Authors: Mendes, Rodrigo E., Toleman, Mark A., Ribeiro, Julival, Sader, Helio S., Jones, Ronald N., Walsh, Timothy R.
• Format: Journal Article
• Language: English
• Published: 01-12-2004
• ISSN: 0066-4804; 1098-6596
• DOI: 10.1128/AAC.48.12.4693-4702.2004

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-β-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 Brasília, 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
bla
IMP-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 μM
−1
 · s
−1
). This report further emphasizes the spread of metallo-β-lactamase genes and their close association with various aminoglycoside resistance genes.