Novel GES/IBC extended-spectrum ?-lactamase variants with carbapenemase activity in clinical enterobacteria

VOURLI, S

doi:10.1016/j.femsle.2004.03.028

Cited by 41 publications

(53 citation statements)

References 7 publications

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“…At least nine GES variants have been described, with GES-9 recently identified in a P. aeruginosa isolate from France (164). Of these closely related enzymes, GES-2, GES-4, GES-5, and GES-6 have substitutions of asparagine or serine at position 170, associated with imipenem hydrolysis (105,218).…”

Section: Plasmid-encoded Enzymes: Kpc and Gesmentioning

confidence: 99%

Carbapenemases: the Versatile β-Lactamases

2007

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SUMMARY Carbapenemases are β-lactamases with versatile hydrolytic capacities. They have the ability to hydrolyze penicillins, cephalosporins, monobactams, and carbapenems. Bacteria producing these β-lactamases may cause serious infections in which the carbapenemase activity renders many β-lactams ineffective. Carbapenemases are members of the molecular class A, B, and D β-lactamases. Class A and D enzymes have a serine-based hydrolytic mechanism, while class B enzymes are metallo-β-lactamases that contain zinc in the active site. The class A carbapenemase group includes members of the SME, IMI, NMC, GES, and KPC families. Of these, the KPC carbapenemases are the most prevalent, found mostly on plasmids in Klebsiella pneumoniae. The class D carbapenemases consist of OXA-type β-lactamases frequently detected in Acinetobacter baumannii. The metallo-β-lactamases belong to the IMP, VIM, SPM, GIM, and SIM families and have been detected primarily in Pseudomonas aeruginosa; however, there are increasing numbers of reports worldwide of this group of β-lactamases in the Enterobacteriaceae. This review updates the characteristics, epidemiology, and detection of the carbapenemases found in pathogenic bacteria.

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Section: Plasmid-encoded Enzymes: Kpc and Gesmentioning

confidence: 99%

Carbapenemases: the Versatile β-Lactamases

2007

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“…Twelve years hence, this growing family of ␤-lactamases now includes 15 members (GES-1 to GES-15), isolated from various Gram-negative bacteria of clinical origins in Europe, Asia, Africa, and the Americas. Although some GES ␤-lactamases produce antibiotic resistance profiles similar to those of classical extended spectrum enzymes (15)(16)(17), some GES variants (GES-2, -4, -5, and -6) also confer decreased susceptibility to imipenem, the first clinical carbapenem. The acquisition of carbapenemase activity by GES enzymes was attributed to a single amino acid substitution at position 170 (Ambler numbering is used) (18).…”

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confidence: 99%

Identification of Products of Inhibition of GES-2 β-Lactamase by Tazobactam by X-ray Crystallography and Spectrometry

Frase

Smith

Tóth

et al. 2011

Journal of Biological Chemistry

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The GES-2 ␤-lactamase is a class A carbapenemase, the emergence of which in clinically important bacterial pathogens is a disconcerting development as the enzyme confers resistance to carbapenem antibiotics. Tazobactam is a clinically used inhibitor of class A ␤-lactamases, which inhibits the GES-2 enzyme effectively, restoring susceptibility to ␤-lactam antibiotics. We have investigated the details of the mechanism of inhibition of the GES-2 enzyme by tazobactam. By the use of UV spectrometry, mass spectroscopy, and x-ray crystallography, we have documented and identified the involvement of a total of seven distinct GES-2⅐tazobactam complexes and one product of the hydrolysis of tazobactam that contribute to the inhibition profile. The x-ray structures for the GES-2 enzyme are for both the native (1.45 Å ) and the inhibited complex with tazobactam (1.65 Å ). This is the first such structure of a carbapenemase in complex with a clinically important ␤-lactam inhibitor, shedding light on the structural implications for the inhibition process.

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“…The modified Hodge test is used for detection of carbapenemase production. It is generally more sensitive for detection of carbapenemases of Ambler class A and class D [16]. It also has other limitations apart its sensitivity to detect class B carbapenemases.…”

Section: Rationalementioning

confidence: 99%