Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA.
Antimicrob Agents Chemother. 2013 Aug;57(8):3783-8. doi: 10.1128/AAC.00808-13. Epub 2013 May 28.
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.
SGM-1 是一种新型的 A 类β-内酰胺酶,来自 Sphingobium sp. 的环境分离株,含有 A 类β-内酰胺酶的所有独特的氨基酸模体。它与所有已测序和注释基因组的 Sphingobium 物种染色体上存在的假定β-内酰胺酶具有 77%至 80%的氨基酸序列同一性。因此,SGM 型β-内酰胺酶是该属的天然产物。抗生素敏感性测试将 SGM-1 归类为扩展谱β-内酰胺酶,对青霉素具有最高水平的抗性。尽管 SGM-1 含有 A 类碳青霉烯酶特征的保守半胱氨酸残基,但它不会赋予对碳青霉烯类抗生素亚胺培南、美罗培南或多尼培南的抗性,但会使厄他培南的 MIC 增加 8 倍。SGM-1 对青霉素和单环β-内酰胺氨曲南的水解效率相似,范围为 10(5)至 10(6) M(-1) s(-1)。SGM-1 对头孢西丁和头孢他啶的催化效率最低(10(2)至 10(3) M(-1) s(-1)),而对所有其他头孢菌素的催化效率在 10(5)至 10(6) M(-1) s(-1)之间变化。SGM-1 对测试的碳青霉烯类药物表现出可测量但无显著活性。SGM-1 对克拉维酸、他唑巴坦和舒巴坦也表现出高亲和力(Ki < 1 μM);然而,只有克拉维酸显著降低了β-内酰胺类药物的 MIC。