Abadía Patiño Lorena, Courvalin Patrice, Perichon Bruno
Unité des Agents Antibactériens, Institut Pasteur, 75724 Paris Cedex 15, France.
J Bacteriol. 2002 Dec;184(23):6457-64. doi: 10.1128/JB.184.23.6457-6464.2002.
Acquired VanE-type resistance to low levels of vancomycin (MIC = 16 microg/ml) in Enterococcus faecalis BM4405 is due to the inducible synthesis of peptidoglyean precursors terminating in D-alanine-D-serine (Fines,M., B. Prichon, P. Reynolds, D. Sahm, and P. Courvalin, Antimicrob. Agents Chemother. 43:2161-2164, 1999). A chromosomal location was assigned to the vanE operon by pulsed-field gel electrophoresis and hybridization, and its sequence was determined. Three genes, encoding the VanE ligase, the VanXYE DD-peptidase, and the VanTE serine racemase, that displayed 43 to 53% identity with the corresponding genes in the vanC operon were found. In addition, two genes coding for a two-component regulatory system, VanRE-VanSE, exhibiting 60 and 44% identity with VanR,-VanS, were present downstream from vanTE. However, because of a stop codon at position 78, VanSE was probably not functional. The five genes, with the same orientation, were shown to be cotranscribed by Northern analysis and reverse transcription-PCR. The vanE, vanXYE, and vanTE genes conferred inducible low-level resistance to vancomycin after cloning in E. faecalis JH2-2, probably following cross talk with a two-component regulatory system of the host.
粪肠球菌BM4405对低水平万古霉素(MIC = 16微克/毫升)获得性VanE型耐药性是由于可诱导合成以D-丙氨酸-D-丝氨酸结尾的肽聚糖前体(Fines,M.,B. Prichon,P. Reynolds,D. Sahm和P. Courvalin,《抗菌剂与化疗》43:2161 - 2164,1999)。通过脉冲场凝胶电泳和杂交将vanE操纵子定位到染色体上,并测定了其序列。发现了三个基因,分别编码VanE连接酶、VanXYE D,D-肽酶和VanTE丝氨酸消旋酶,它们与vanC操纵子中的相应基因具有43%至53%的同一性。此外,在vanTE下游存在两个编码双组分调节系统VanRE - VanSE的基因,它们与VanR - VanS的同一性分别为60%和44%。然而,由于第78位存在终止密码子,VanSE可能无功能。通过Northern分析和逆转录PCR表明,这五个基因方向相同,是共转录的。vanE、vanXYE和vanTE基因在克隆到粪肠球菌JH2 - 2后赋予了对万古霉素的可诱导低水平耐药性,这可能是与宿主的双组分调节系统发生串扰的结果。