title: A novel extended-spectrum β-lactamase, SGM-1, from an environmental isolate of Sphingobium sp.
abstract: SGM-1 is a novel class A β-lactamase from an environmental isolate of Sphingobium sp. containing all of the distinct amino acid motifs of class A β-lactamases. It shares 77 to 80% amino acid sequence identity with putative β-lactamases that are present on the chromosome of all Sphingobium species whose genomes were sequenced and annotated. Thus, SGM-type β-lactamases are native to this genus. Antibiotic susceptibility testing classifies SGM-1 as an extended-spectrum β-lactamase, conferring the highest level of resistance to penicillins. Although SGM-1 contains the conserved cysteine residues characteristic of class A carbapenemases, it does not confer resistance to the carbapenem antibiotics imipenem, meropenem, or doripenem but does increase the MIC of ertapenem 8-fold. SGM-1 hydrolyzes penicillins and the monobactam aztreonam with similar catalytic efficiencies, ranging from 10(5) to 10(6) M(-1) s(-1). The catalytic efficiencies of SGM-1 for cefoxitin and ceftazidime were the lowest (10(2) to 10(3) M(-1) s(-1)) among the cephalosporins tested, while the catalytic efficiencies against all other cephalosporins varied from about 10(5) to 10(6) M(-1) s(-1). SGM-1 exhibited measurable but not significant activity toward the carbapenems tested. SGM-1 also showed high affinity for clavulanic acid, tazobactam, and sulbactam (Ki < 1 μM); however, only clavulanic acid significantly reduced the MICs of β-lactams.
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA.
authors.forename: Toni L
authors.initials: TL
authors.lastname: Lamoureaux
authors.forename: Viktoria
authors.initials: V
authors.lastname: Vakulenko
authors.forename: Marta
authors.initials: M
authors.lastname: Toth
authors.forename: Hilary
authors.initials: H
authors.lastname: Frase
authors.forename: Sergei B
authors.initials: SB
authors.lastname: Vakulenko
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002442:Ceftazidime / Q000494:pharmacology; D019818:Clavulanic Acid / Q000494:pharmacology; D003001:Cloning, Molecular; D003545:Cysteine / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects; D005798:Genes, Bacterial; D015378:Imipenem / Q000494:pharmacology; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D020539:Sequence Analysis, Protein; D042301:Sphingomonadaceae / Q000201:enzymology* / Q000235:genetics; D013845:Thienamycins / Q000494:pharmacology; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D013845:Thienamycins; D019818:Clavulanic Acid; D015378:Imipenem; D002442:Ceftazidime; D001618:beta-Lactamases; D000077731:Meropenem; D003545:Cysteine