Sahm D F, Free L, Handwerger S
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Antimicrob Agents Chemother. 1995 Jul;39(7):1480-4. doi: 10.1128/AAC.39.7.1480.
Clinical isolates Enterococcus gallinarum AIB39 and E. gallinarum GS1 were studied to establish whether the expression of vanC-1-mediated resistance may be inducible or constitutive. By growth curve analysis, strain AIB39 exhibited the same lag period (i.e., 1 to 1.5 h) whether it was subcultured to unsupplemented brain heart infusion broth or broth containing 6 micrograms of vancomycin per ml, a growth pattern typical of constitutively expressed resistance. Use of high-performance liquid chromatography (HPLC) to separate peptidoglycan precursor extracts substantiated this finding because the serine-terminating pentapeptide precursor UDP-MurNAc-L-Ala-D-Glu-L-Lys-D-Ala-D-Ser was produced in the presence and absence of vancomycin, whereas no UDP-MurNAc-L-Ala-D-Glu-L-Lys-D-Ala-D-Ala was detected. In contrast, results with strain GS1 were consistent with inducible expression. GS1 demonstrated a lag time that was 3 to 4 h longer when it was subcultured to vancomycin-containing broth than when it was subcultured in unsupplemented broth. HPLC analysis showed that in the absence of vancomycin only UDP-MurNAc-L-Ala-D-Glu-L-Lys-D-Ala-D-Ala was detected, but in the presence of drug only UDP-MurNAc-L-Ala-D-Glu-L-Lys-D-Ala-D-Ala was found. Inducible expression of vanC-1-mediated resistance in E. gallinarum is consistent with recent findings suggesting the presence of at least two ligases in this species. Although vanC-1 may be intrinsic to E. gallinarum, our findings raise doubt regarding the natural mechanism of this gene's expression.
对临床分离株鹑鸡肠球菌AIB39和鹑鸡肠球菌GS1进行了研究,以确定vanC-1介导的耐药性表达是可诱导的还是组成型的。通过生长曲线分析,菌株AIB39无论转接至未添加抗生素的脑心浸液肉汤还是每毫升含6微克万古霉素的肉汤中,其延迟期均相同(即1至1.5小时),这是组成型表达耐药性的典型生长模式。使用高效液相色谱法(HPLC)分离肽聚糖前体提取物证实了这一发现,因为在有和没有万古霉素的情况下均产生了丝氨酸末端的五肽前体UDP-MurNAc-L-Ala-D-Glu-L-Lys-D-Ala-D-Ser,而未检测到UDP-MurNAc-L-Ala-D-Glu-L-Lys-D-Ala-D-Ala。相比之下,菌株GS1的结果与诱导型表达一致。GS1转接至含万古霉素的肉汤中时的延迟时间比转接至未添加抗生素的肉汤中时延长3至4小时。HPLC分析表明,在没有万古霉素的情况下仅检测到UDP-MurNAc-L-Ala-D-Glu-L-Lys-D-Ala-D-Ala,但在有药物的情况下也仅发现UDP-MurNAc-L-Ala-D-Glu-L-Lys-D-Ala-D-Ala。鹑鸡肠球菌中vanC-1介导的耐药性的诱导型表达与最近的研究结果一致,这些结果表明该物种中至少存在两种连接酶。虽然vanC-1可能是鹑鸡肠球菌固有的,但我们的研究结果对该基因表达的自然机制提出了质疑。