PDF(Pubmed)
Abstract：
Intravenous gallium therapy is a non-antibiotic approach to limit Pseudomonas aeruginosa biofilm proliferation, by outcompeting iron for siderophore binding. Gallium therapy represents a viable therapeutic strategy for cystic fibrosis (CF) patients harbouring mucoid P. aeruginosa biofilm lung infections. Siderophore deficient P. aeruginosa isolates still demonstrate a hindered biofilm proliferation when exposed to gallium but it is currently unknown whether exogenous gallium has any disruptive influence on the exopolysaccharide (EPS), the major mucoid P. aeruginosa CF lung biofilm matrix component. To that end, Density-Functional Theory (DFT) was deployed to assess whether gallium (Ga3+) could be substituted into the mature mucoid EPS scaffold in preference of calcium (Ca2+)-the native EPS cross-linking ion. Removal of the stable, bound native calcium ions offers a large enthalpic barrier to the substitution and the mature EPS fails to accommodate exogenous gallium. This suggests that gallium, perhaps, is utilising a novel, possibly unknown, ferric uptake system to gain entry to siderophore deficient cells.
摘要：
静脉镓治疗是一种限制铜绿假单胞菌生物膜增殖的非抗生素方法，通过竞争铁载体结合。镓疗法代表了对具有粘液样铜绿假单胞菌生物膜肺感染的囊性纤维化(CF)患者的可行治疗策略。当暴露于镓时，嗜铁性铜绿假单胞菌分离物仍然表现出生物膜增殖受阻，但目前尚不清楚外源镓是否对外多糖（EPS）有任何破坏性影响，主要的粘液类铜绿假单胞菌CF肺生物膜基质成分。为此,采用密度泛函理论（DFT）来评估镓（Ga3）是否可以优先于钙（Ca2）-天然EPS交联离子取代成熟的粘液EPS支架。去除稳定，结合的天然钙离子为取代提供了大的焓屏障，成熟的EPS无法容纳外源镓。这表明镓，也许,正在利用一本小说，可能未知,铁摄取系统进入铁载体缺陷细胞。
