Antimicrobial efficacy against Pseudomonas aeruginosa biofilm formation in a three-dimensional lung epithelial model and the influence of fetal bovine serum.
Antimicrobial efficacy against Pseudomonas aeruginosa biofilm formation in a three-dimensional lung epithelial model and the influence of fetal bovine serum.
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DOI：
10.1038/srep43321
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发表时间：
2017-03-03
影响因子：
4.6
通讯作者：
Nickerson CA
中科院分区：
文献类型：
--
作者：
Crabbé A;Liu Y;Matthijs N;Rigole P;De La Fuente-Nùñez C;Davis R;Ledesma MA;Sarker S;Van Houdt R;Hancock RE;Coenye T;Nickerson CA
需要模拟体内宿主-病原体相互作用的体外模型来评价抑制细菌毒力性状的候选药物。我们建立了一种新的方法来研究铜绿假单胞菌生物膜的生物表面的敏感性，使用三维（3-D）肺上皮细胞模型。铜绿假单胞菌在3-D细胞上形成抗生素抗性生物膜而不影响细胞活力。抗生素和/或抗生物膜肽DJK-5的生物膜抑制活性在3-D细胞上进行了评价，与塑料表面相比，在有和没有胎牛血清（FBS）的培养基中。在两种培养基中，氨基糖苷类在3-D细胞模型中更有效。在无血清培养基中，大多数抗生素（除多粘菌素）表现出增强的疗效时，3-D细胞。在含有FBS的培养基中，粘菌素在3-D细胞模型中的有效性较低。DJK-5仅在无血清培养基中对铜绿假单胞菌与两种底物的结合产生有效抑制。与3-D细胞相比，DJK-5对与塑料相关的铜绿假单胞菌显示出更强的抑制活性。妥布霉素和DJK-5的组合添加表现出更有效的抑制铜绿假单胞菌与两种底物结合的能力。总之，肺上皮细胞影响大多数抗微生物剂对铜绿假单胞菌生物膜形成的功效，这反过来又取决于FBS的存在或不存在。
In vitro models that mimic in vivo host-pathogen interactions are needed to evaluate candidate drugs that inhibit bacterial virulence traits. We established a new approach to study Pseudomonas aeruginosa biofilm susceptibility on biotic surfaces, using a three-dimensional (3-D) lung epithelial cell model. P. aeruginosa formed antibiotic resistant biofilms on 3-D cells without affecting cell viability. The biofilm-inhibitory activity of antibiotics and/or the anti-biofilm peptide DJK-5 were evaluated on 3-D cells compared to a plastic surface, in medium with and without fetal bovine serum (FBS). In both media, aminoglycosides were more efficacious in the 3-D cell model. In serum-free medium, most antibiotics (except polymyxins) showed enhanced efficacy when 3-D cells were present. In medium with FBS, colistin was less efficacious in the 3-D cell model. DJK-5 exerted potent inhibition of P. aeruginosa association with both substrates, only in serum-free medium. DJK-5 showed stronger inhibitory activity against P. aeruginosa associated with plastic compared to 3-D cells. The combined addition of tobramycin and DJK-5 exhibited more potent ability to inhibit P. aeruginosa association with both substrates. In conclusion, lung epithelial cells influence the efficacy of most antimicrobials against P. aeruginosa biofilm formation, which in turn depends on the presence or absence of FBS.