Chronic Pseudomonas aeruginosa lung infections in cystic fibrosis (CF) evolve to generate environmentally adapted biofilm communities, leading to increased patient morbidity and mortality. OligoG CF-5/20, a low-molecular-weight inhaled alginate oligomer therapy, is currently in phase IIb/III clinical trials in CF patients. Experimental evolution of P. aeruginosa in response to OligoG CF-5/20 was assessed using a bead biofilm model allowing continuous passage (45 days; ∼245 generations). Mutants isolated after OligoG CF-5/20 treatment typically had a reduced biofilm-forming ability and altered motility profile. Genotypically, OligoG CF-5/20 provided no selective pressure on genomic mutations within morphotypes. Chronic exposure to azithromycin, a commonly prescribed antibiotic in CF patients, with or without OligoG CF-5/20 in the biofilm evolution model also had no effect on rates of resistance acquisition. Interestingly, however, cross-resistance to other antibiotics (e.g., aztreonam) was reduced in the presence of OligoG CF-5/20. Collectively, these findings show no apparent adverse effects from long-term exposure to OligoG CF-5/20, instead resulting in both fewer colonies with multidrug resistance (MDR)-associated phenotypes and improved antibiotic susceptibility of P. aeruginosa.

中文翻译：

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长期暴露于藻酸盐低聚物疗法后铜绿假单胞菌生物膜的表型和基因型适应

囊性纤维化 (CF) 中的慢性铜绿假单胞菌肺部感染进化以产生适应环境的生物膜群落，导致患者发病率和死亡率增加。OligoG CF-5/20 是一种低分子量吸入藻酸盐低聚物疗法，目前正在 CF 患者中进行 IIb/III 期临床试验。铜绿假单胞菌的实验进化使用允许连续传代（45 天；～245 代）的珠子生物膜模型评估对 OligoG CF-5/20 的反应。OligoG CF-5/20 处理后分离的突变体通常具有降低的生物膜形成能力和改变的运动特性。在基因型上，OligoG CF-5/20 对形态型内的基因组突变没有选择压力。长期接触阿奇霉素（CF 患者常用的一种抗生素），在生物膜进化模型中有或没有 OligoG CF-5/20 也对耐药性获得率没有影响。然而，有趣的是，在 OligoG CF-5/20 的存在下，对其他抗生素（例如氨曲南）的交叉耐药性降低。总的来说，这些发现表明长期暴露于 OligoG CF-5/20 没有明显的不利影响，铜绿假单胞菌。