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.
In Vivo Inflammation Caused by Achromobacter spp. Cystic Fibrosis Clinical Isolates Exhibiting Different Pathogenic Characteristics
	
	
	
		
		
		
		
		
	
	
	
	
	
	
	
	
		
		
		
		
		
			
			
			
		
		
		
		
			
			
				
				
					
					
					
					
						
							
						
						
					
				
				
				
				
				
				
				
				
				
				
				
			
			
		
			
			
				
				
					
					
					
					
						
							
						
						
					
				
				
				
				
				
				
				
				
				
				
				
			
			
		
			
			
				
				
					
					
					
					
						
							
						
						
					
				
				
				
				
				
				
				
				
				
				
				
			
			
		
			
			
				
				
					
					
					
					
						
							
						
						
					
				
				
				
				
				
				
				
				
				
				
				
			
			
		
			
			
				
				
					
					
					
					
						
							
						
						
					
				
				
				
				
				
				
				
				
				
				
				
			
			
		
			
			
				
				
					
					
					
					
						
							
						
						
					
				
				
				
				
				
				
				
				
				
				
				
			
			
		
			
			
				
				
					
					
					
					
						
							
						
						
					
				
				
				
				
				
				
				
				
				
				
				
			
			
		
			
			
				
				
					
					
					
					
						
							
						
						
					
				
				
				
				
				
				
				
				
				
				
				
			
			
		
			
			
				
				
					
					
					
					
						
							
						
						
					
				
				
				
				
				
				
				
				
				
				
				
			
			
		
			
			
				
				
					
					
					
					
						
							
						
						
					
				
				
				
				
				
				
				
				
				
				
				
			
			
		
			
			
				
				
					
					
					
					
						
							
						
						
					
				
				
				
				
				
				
				
				
				
				
				
			
			
		
		
		
		
	
Sandri, Angela;Saitta, Giulia Maria;Veschetti, Laura;Boschi, Federico;Passarelli Mantovani, Rebeca;Carelli, Maria;Melotti, Paola;Signoretto, Caterina;Boaretti, Marzia;Malerba, Giovanni;Lleò, Maria M
			2023-01-01
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.| File | Dimensione | Formato | |
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