The Dot/Icm system is essential in the outcome of Legionella pneumophila pneumonia in vivo
Abstract number: P1928
Ader F., Ginevra C., Molmeret M., Doleans A., Guery B., Jarraud S., Etienne J., Chidiac C.
Objective:Legionella pneumophila (L. p) is a facultative intracellular Gram-negative pathogen responsible for life-threatening pneumonia. The Legionella pneumophila Dot/Icm system is an important macromolecular transporter associated with virulence. The aim of the study was to determine the in vivo involvement of Dot/Icm system in L. p pathogenesis for 3 clinical isolates responsible for endemic (L. p Paris) and epidemic (L. p Lens and Philadelphia) cases.
Methods: A/J mice were infected by an intra-tracheal instillation of 106 bacteria using clinical isolates, L. p Paris, Lens and Philadelphia strains (serogroup 1) and their isogenic mutant invalidated in dotB gene. Acute lung injury was assessed in a control group and at 24 and 48 h post-infection by measuring: (i) the protein levels in bronchoalveolar lavage fluids (BALF); (ii) the lung endothelial permeability to radio labelled I125 albumin (Perm-I125); (iii) the alveolar inflammatory response through levels of tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-6, IL-12p70 cytokines in BALF. Systemic spread was assessed by blood, liver, kidneys, spleen and brain cultures.
Results: Protein levels in BALF and Perm-I125 were significantly lower at 48 h in the mutant strain infected groups than in the wild type infected groups (P < 0.001 and P < 0.05 respectively). Levels of IFN-gamma, IL-6, IL-12p70 in BALF, except TNF-alpha, were significantly lower at 48 h in the mutant strain infected groups than in the wild type infected groups (P < 0.001). Bacterial localisation in blood, liver, kidneys, spleen and brain cultures were significantly reduced at 24 and 48 h in the mutant strain infected groups than in the wild type infected groups (P < 0.001).
Conclusion: The Dot/Icm system of endemic and epidemic strains of L. p serogroup1 is a critical virulence factor in vivo, associated with the development of alveolar-capillary barrier injury, alveolar proinflammatory response and bacterial dissemination emphasising its relevance as a major potential therapeutic target.
|Session name:||18th European Congress of Clinical Microbiology and Infectious Diseases|
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