Susceptibility of Pseudomonas aeruginosa Dispersed Cells to Antimicrobial Agents Is Dependent on the Dispersion Cue and Class of the Antimicrobial Agent Used
Susceptibility of Pseudomonas aeruginosa Dispersed Cells to Antimicrobial Agents Is Dependent on the Dispersion Cue and Class of the Antimicrobial Agent Used
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DOI：
10.1128/aac.00846-17
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发表时间：
2017-12-01
影响因子：
4.9
通讯作者：
Sauer, Karin
中科院分区：
文献类型：
--
作者：
Chambers, Jacob R.;Cherny, Kathryn E.;Sauer, Karin
生物膜生命周期的特点是对抗菌剂高度敏感的浮游细胞向对抗菌剂高度耐受的生物膜生长模式转变，随后细胞从生物膜分散回环境中。然而，分散细胞与浮游细胞并不相同，但其特征是相对于生物膜和浮游细胞具有独特的过渡表型，分散细胞以类似于指数期细胞的方式附着，但表现出与指数期和稳定期浮游细胞不同的基因表达模式。这就提出了分散细胞是否与浮游细胞一样敏感以及分散诱导剂或抗生素类别是否影响分散细胞的药物敏感性的问题。因此，响应分散线索谷氨酸和一氧化氮（NO）而获得的分散细胞暴露于妥布霉素和粘菌素。虽然NO诱导的分散细胞与指数期浮游细胞一样对粘菌素和妥布霉素敏感，但谷氨酸诱导的分散细胞对妥布霉素敏感但对粘菌素耐药。粘菌素敏感性的差异与细胞 c-di-GMP 水平无关，c-di-GMP 的调节无法诱导分散。相反，药物敏感性与 LPS 修饰系统和生物膜特异性转录调节因子 BrlR 呈负相关。谷氨酸诱导的分散细胞对粘菌素的敏感性表型被发现是可逆的，分散的细胞在分散后 2 小时内变得对粘菌素敏感，尽管分散的细胞需要额外的时间来显示指示指数生长的基因表达。
The biofilm life cycle is characterized by the transition of planktonic cells exhibiting high susceptibly to antimicrobial agents to a biofilm mode of growth characterized by high tolerance to antimicrobials, followed by dispersion of cells from the biofilm back into the environment. Dispersed cells, however, are not identical to planktonic cells but have been characterized as having a unique transitionary phenotype relative to biofilm and planktonic cells, with dispersed cells attaching in a manner similar to exponential-phase cells, but demonstrating gene expression patterns that are distinct from both exponential and stationary-phase planktonic cells. This raised the question whether dispersed cells are as susceptible as planktonic cells and whether the dispersion inducer or the antibiotic class affects the drug susceptibility of dispersed cells. Dispersed cells obtained in response to dispersion cues glutamate and nitric oxide (NO) were thus exposed to tobramycin and colistin. Although NO-induced dispersed cells were as susceptible to colistin and tobramycin as exponential-phase planktonic cells, glutamate-induced dispersed cells were susceptible to tobramycin but resistant to colistin. The difference in colistin susceptibility was independent of cellular c-di-GMP levels, with modulation of c-di-GMP failing to induce dispersion. Instead, drug susceptibility was inversely correlated with LPS modification system and the biofilm-specific transcriptional regulator BrlR. The susceptibility phenotype of glutamate-induced dispersed cells to colistin was found to be reversible, with dispersed cells being rendered as susceptible to colistin within 2 h postdispersion, though additional time was required for dispersed cells to display expression of genes indicative of exponential growth.