Department of Chemistry and Nano Science, Ewha Womans University, Seoul, Korea.
PLoS One. 2011;6(7):e21387. doi: 10.1371/journal.pone.0021387. Epub 2011 Jul 7.
Pseudomonas aeruginosa (PA) and Burkholderia cepacia complex (Bcc), commonly found in the lungs of cystic fibrosis (CF) patients, often produce cyanide (CN), which inhibits cellular respiration. CN in sputa is a potential biomarker for lung infection by CF pathogens. However, its actual concentration in the infected lungs is unknown.
This work reports observation of CN in the lungs of mice infected with cyanogenic PA or Bcc strains using a CN fluorescent chemosensor (4',5'-fluorescein dicarboxaldehyde) with a whole animal imaging system. When the CN chemosensor was injected into the lungs of mice intratracheally infected with either PA or B. cepacia strains embedded in agar beads, CN was detected in the millimolar range (1.8 to 4 mM) in the infected lungs. CN concentration in PA-infected lungs rapidly increased within 24 hours but gradually decreased over the following days, while CN concentration in B. cepacia-infected lungs slowly increased, reaching a maximum at 5 days. CN concentrations correlated with the bacterial loads in the lungs. In vivo efficacy of antimicrobial treatments was tested in live mice by monitoring bacteriogenic CN in the lungs.
The in vivo imaging method was also found suitable for minimally invasive testing the efficacy of antibiotic compounds as well as for aiding the understanding of bacterial cyanogenesis in CF lungs.
铜绿假单胞菌（PA）和洋葱伯克霍尔德菌复合群（Bcc）通常存在于囊性纤维化（CF）患者的肺部，它们经常产生氰化物（CN），抑制细胞呼吸。痰液中的 CN 是 CF 病原体肺部感染的潜在生物标志物。然而，其在感染肺部的实际浓度尚不清楚。
本研究使用带有小动物活体成像系统的 CN 荧光化学传感器（4',5'-荧光素二羧酸酐），对感染氰化物产生菌的小鼠肺部中的 CN 进行了观察。当将 CN 化学传感器通过气管内注射到含有琼脂珠的 PA 或 B. cepacia 菌株感染的小鼠肺部时，在感染的肺部中检测到毫摩尔级（1.8 至 4 mM）的 CN。PA 感染的肺部中 CN 浓度在 24 小时内迅速增加，但随后几天逐渐降低，而 B. cepacia 感染的肺部中 CN 浓度缓慢增加，在第 5 天达到最大值。CN 浓度与肺部中的细菌负荷相关。通过监测肺部产生的细菌源性 CN，在活小鼠中测试了抗菌治疗的体内疗效。
该体内成像方法也适用于微创测试抗生素化合物的疗效，并有助于理解 CF 肺部中的细菌产氰作用。
