Binghamton Biofilm Research Center, Department of Biological Sciences, Binghamton University, Binghamton, New York, USA.
Binghamton Biofilm Research Center, Department of Biological Sciences, Binghamton University, Binghamton, New York, USA
Antimicrob Agents Chemother. 2017 Nov 22;61(12). doi: 10.1128/AAC.00846-17. Print 2017 Dec.
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.
生物膜的生命周期以浮游细胞的易感性向抗微生物剂转变为生物膜生长模式为特征，其对抗微生物剂的耐受性较高，然后细胞从生物膜分散回环境中。然而，分散的细胞与浮游细胞并不相同，而是具有相对于生物膜和浮游细胞的独特过渡表型，与指数期细胞相似的方式附着，但表现出与指数期和静止期浮游细胞都不同的基因表达模式。这就提出了一个问题，即分散细胞是否像浮游细胞那样容易受到影响，以及分散诱导剂或抗生素类别是否会影响分散细胞的药物敏感性。因此，对响应分散信号谷氨酸和一氧化氮 (NO) 获得的分散细胞进行了妥布霉素和黏菌素的暴露实验。虽然 NO 诱导的分散细胞对黏菌素和妥布霉素的敏感性与指数期浮游细胞相同，但谷氨酸诱导的分散细胞对妥布霉素敏感，但对黏菌素有抗性。对黏菌素敏感性的差异与细胞 c-di-GMP 水平无关，c-di-GMP 的调节不能诱导分散。相反，药物敏感性与脂多糖修饰系统和生物膜特异性转录调节剂 BrlR 呈负相关。发现谷氨酸诱导的分散细胞对黏菌素的敏感性表型是可逆的，分散细胞在分散后 2 小时内对黏菌素的敏感性增加，尽管需要更多的时间使分散细胞表现出指示指数生长的基因表达。
