In Vivo Inflammation Caused by Achromobacter spp. Cystic Fibrosis Clinical Isolates Exhibiting Different Pathogenic Characteristics

无色杆菌属引起的体内炎症。囊性纤维化临床分离株表现出不同的致病特征

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作者:Angela Sandri, Giulia Maria Saitta, Laura Veschetti, Federico Boschi, Rebeca Passarelli Mantovani, Maria Carelli, Paola Melotti, Caterina Signoretto, Marzia Boaretti, Giovanni Malerba, Maria M Lleò

Abstract

Achromobacter 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 Galleria mellonella larvae, cytotoxicity in human bronchial epithelial cells, and biofilm formation. Acute lung infection was established by intratracheal instillation with 10.5 × 108 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 Achromobacter spp. pathogenic characteristics such as virulence and cytotoxicity may be associated with clinically relevant effects and highlight the importance of elucidating their mechanisms.

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