Department of Diagnostics and Public Health, Microbiology Section, University of Verona, 37134 Verona, Italy.
GMLab, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy.
Int J Mol Sci. 2023 Apr 18;24(8):7432. doi: 10.3390/ijms24087432.
spp. lung infection in cystic fibrosis has been associated with inflammation, increased frequency of exacerbations, and decline of respiratory function. We aimed to evaluate in vivo the inflammatory effects of clinical isolates exhibiting different pathogenic characteristics. Eight clinical isolates were selected based on different pathogenic characteristics previously assessed: virulence in larvae, cytotoxicity in human bronchial epithelial cells, and biofilm formation. Acute lung infection was established by intratracheal instillation with 10.5 × 10 bacterial cells in wild-type and CFTR-knockout (KO) mice expressing a luciferase gene under control of interleukin-8 promoter. Lung inflammation was monitored by in vivo bioluminescence imaging up to 48 h after infection, and mortality was recorded up to 96 h. Lung bacterial load was evaluated by CFU count. Virulent isolates caused higher lung inflammation and mice mortality, especially in KO animals. Isolates both virulent and cytotoxic showed higher persistence in mice lungs, while biofilm formation was not associated with lung inflammation, mice mortality, or bacterial persistence. A positive correlation between virulence and lung inflammation was observed. These results indicate that spp. pathogenic characteristics such as virulence and cytotoxicity may be associated with clinically relevant effects and highlight the importance of elucidating their mechanisms.
在囊性纤维化中, spp.肺部感染与炎症、恶化频率增加和呼吸功能下降有关。我们旨在评估具有不同致病特征的临床分离株的体内炎症效应。根据先前评估的不同致病特征选择了 8 株临床分离株:幼虫中的毒力、人支气管上皮细胞中的细胞毒性和生物膜形成。通过气管内滴注 10.5×10 个细菌细胞,在表达白细胞介素-8 启动子控制下的荧光素酶基因的野生型和 CFTR 敲除(KO)小鼠中建立急性肺部感染。在感染后长达 48 小时内通过体内生物发光成像监测肺部炎症,并记录高达 96 小时的死亡率。通过 CFU 计数评估肺部细菌负荷。毒力分离株引起更高的肺部炎症和小鼠死亡率,尤其是在 KO 动物中。毒力和细胞毒性的分离株在小鼠肺部的持续时间更长,而生物膜形成与肺部炎症、小鼠死亡率或细菌持续时间无关。观察到毒力与肺部炎症之间存在正相关。这些结果表明, spp. 的致病特征,如毒力和细胞毒性,可能与临床相关的效应有关,并强调阐明其机制的重要性。