Fassi Fehri Lina, Wróblewski Henri, Blanchard Alain
INRA Université de Bordeaux 2, UMR Génomique Développement Pouvoir Pathogène, 71 avenue Edouard Bourlaux, BP 81, 33883 Villenave D'Ornon, France.
Antimicrob Agents Chemother. 2007 Feb;51(2):468-74. doi: 10.1128/AAC.01030-06. Epub 2006 Nov 13.
We showed in a previous study that associations of antimicrobial peptides (AMPs), which are key components of the innate immune systems of all living species, with the fluoroquinolone enrofloxacin can successfully cure HeLa cell cultures of Mycoplasma fermentans and M. hyorhinis contamination. In the present work, the in vitro susceptibility of M. pulmonis, a murine pathogen, to enrofloxacin and four AMPs (alamethicin, globomycin, gramicidin S, and surfactin) was investigated, with special reference to synergistic associations and the effect of the mycoplasma cell concentration. Enrofloxacin and globomycin displayed the lowest MICs (0.4 microM), followed by gramicidin S (3.12 microM), alamethicin (6.25 microM), and surfactin (25 microM). When the mycoplasma cell concentration was varied from 10(4) to 10(8) CFU/ml, the MICs of enrofloxacin and globomycin increased while those of the three other molecules remained essentially constant. The minimal bactericidal concentration of enrofloxacin (0.8 microM) was also lower than those of the peptides (6.25 to 100 microM), but the latter killed the mycoplasma cells much faster than enrofloxacin (2 h versus 1 day). The use of the AMPs in association with enrofloxacin revealed synergistic effects with alamethicin and surfactin. Interestingly, the mycoplasma-killing activities of the two combinations enrofloxacin (MIC/2) plus alamethicin (MIC/4) and enrofloxacin (MIC/2) plus surfactin (MIC/16) were about 2 orders of magnitude higher than those of the three molecules used separately. These results support the interest devoted to AMPs as a novel class of antimicrobial agents and pinpoint their ability to potentiate the activities of conventional antibiotics, such as fluoroquinolones.
我们在之前的一项研究中表明，抗菌肽（AMPs）是所有生物先天免疫系统的关键组成部分，其与氟喹诺酮类药物恩诺沙星联合使用可成功清除人宫颈癌细胞系（HeLa细胞）中的发酵支原体和猪鼻支原体污染。在本研究中，我们考察了鼠病原体肺支原体对恩诺沙星和四种抗菌肽（阿拉霉素、球霉素、短杆菌肽S和表面活性素）的体外敏感性，特别关注协同联合作用以及支原体细胞浓度的影响。恩诺沙星和球霉素的最低抑菌浓度（MIC）最低（0.4 μM），其次是短杆菌肽S（3.12 μM）、阿拉霉素（6.25 μM）和表面活性素（25 μM）。当支原体细胞浓度从10⁴ 至10⁸ CFU/ml变化时，恩诺沙星和球霉素的MIC升高，而其他三种分子的MIC基本保持不变。恩诺沙星的最小杀菌浓度（0.8 μM）也低于肽类（6.25至100 μM），但肽类杀灭支原体细胞的速度比恩诺沙星快得多（2小时对1天）。抗菌肽与恩诺沙星联合使用显示出与阿拉霉素和表面活性素的协同作用。有趣的是，恩诺沙星（MIC/2）加阿拉霉素（MIC/4）和恩诺沙星（MIC/2）加表面活性素（MIC/16）这两种组合的杀支原体活性比单独使用这三种分子时高约2个数量级。这些结果支持了将抗菌肽作为一类新型抗菌剂的研究，并指出了它们增强传统抗生素（如氟喹诺酮类）活性的能力。
