Foucault Marie-Laure, Courvalin Patrice, Grillot-Courvalin Catherine
Unité des Agents Antibactériens, Institut Pasteur, 25 Rue du Docteur Roux, 75724 Paris Cedex 15, France.
Antimicrob Agents Chemother. 2009 Jun;53(6):2354-9. doi: 10.1128/AAC.01702-08. Epub 2009 Mar 30.
We have quantified the biological cost of VanA-type glycopeptide resistance due to the acquisition of the resistance operon by methicillin-resistant Staphylococcus aureus (MRSA) from Enterococcus sp. Exponential growths of recipient strain HIP11713, its transconjugant VRSA-1, VRSA-5, and VRSA-6 were compared in the absence or, except for HIP11713, in the presence of vancomycin. Induction of resistance was performed by adding vancomycin in both the preculture and the culture or the culture at only 1/50 the MIC. In the absence of vancomycin, the growth rates of the vancomycin-resistant S. aureus (VRSA) strains were similar to that of susceptible MRSA strain HIP11713. When resistance was induced, and under both conditions, there was a significant reduction of the growth rate of the VRSA strains relative to that of HIP11713 and to those of their noninduced counterparts, corresponding to a ca. 20% to 38% reduction in fitness. Competition experiments between isogenic VRSA-1 and HIP11713 mixed at a 1:1, 1:100, or 100:1 ratio revealed a competitive disadvantage of 0.4% to 3% per 10 generations of the transconjugant versus the recipient. This slight fitness burden can be attributed to the basal level of expression of the van genes in the absence of induction combined with a gene dosage effect due to the presence of the van operon on multicopy plasmids. These data indicate that VanA-type resistance, when induced, is highly costly for the MRSA host, whereas in the absence of induction, its biological cost is minimal. Thus, the potential for the dissemination of VRSA clinical isolates should not be underestimated.
我们已经对耐甲氧西林金黄色葡萄球菌（MRSA）从肠球菌属获得耐药操纵子而产生的VanA 型糖肽耐药的生物学代价进行了量化。在不存在万古霉素的情况下，或者除了HIP11713菌株外，在存在万古霉素的情况下，比较了受体菌株HIP11713、其转接合子VRSA-1、VRSA-5和VRSA-6的指数生长情况。通过在预培养和培养过程中添加万古霉素，或者仅在1/50最小抑菌浓度（MIC）的培养过程中添加万古霉素来诱导耐药性。在不存在万古霉素的情况下，耐万古霉素金黄色葡萄球菌（VRSA）菌株的生长速率与敏感的MRSA菌株HIP11713相似。当诱导产生耐药性时，在两种条件下，VRSA菌株的生长速率相对于HIP11713及其未诱导的对应菌株均显著降低，相当于适应性降低约20%至38%。等基因VRSA-1和HIP11713以1:1、1:100或100:1的比例混合进行的竞争实验表明，转接合子相对于受体每10代的竞争劣势为0.4%至3%。这种轻微的适应性负担可归因于在未诱导情况下van基因的基础表达水平，以及由于多拷贝质粒上存在van操纵子而产生的基因剂量效应。这些数据表明，VanA 型耐药性在诱导时对MRSA宿主来说代价高昂，而在未诱导时，其生物学代价最小。因此，VRSA临床分离株传播的可能性不应被低估。
