Pathophysiology of Escherichia coli pneumonia: Respective contribution of pathogenicity islands to virulence.

Ventilator-associated pneumonia (VAP) remains the most frequent life-threatening nosocomial infection. Enterobacteriaceae including Escherichia coli are increasingly involved. If a cumulative effect of pathogenicity islands (PAIs) has been shown for E. coli virulence in urinary tract or systemic infections, very little is known regarding pathophysiology of E. coli pneumonia. This study aimed to determine the role of each of the 7 PAIs present in pathogenic E. coli strain 536 in pneumonia pathophysiology. We used mutant strains to screen pathophysiological role of PAI in a rat pneumonia model. We also test individual gene mutants within PAI identified to be involved in pneumonia pathogenesis. Finally, we determined the prevalence of these genes of interest in E. coli isolates from feces and airways of ventilated patients. Only PAIs I and III were significantly associated with rat pneumonia pathogenicity. Only the antigen-43 (Ag43) gene in PAI III was significantly associated with bacterial pathogenicity. The prevalence of tested genes in fecal and airway isolates of ventilated patients did not differ between isolates. In contrast, genes encoding Ag43, the F17-fimbriae subunits, HmuR and SepA were more prevalent in VAP isolates with statistical significance for hmuR when compared to airway colonizing isolates. The E. coli PAIs involved in lung pathogenicity differed from those involved in urinary tract and bloodstream infections. Overall, extraintestinal E. coli virulence seems to rely on a combination of numerous virulence genes that have a cumulative effect depending on the infection site.

Airway fungal colonization compromises the immune system allowing bacterial pneumonia to prevail.

OBJECTIVE: To study the correlation between fungal colonization and bacterial pneumonia and to test the effect of antifungal treatments on the development of bacterial pneumonia in colonized rats. DESIGN: Experimental animal investigation. SETTING: University research laboratory. SUBJECTS: Pathogen-free male Wistar rats weighing 250-275 g. INTERVENTIONS: Rats were colonized by intratracheal instillation of Candida albicans. Fungal clearance from the lungs and immune response were measured. Both colonized and noncolonized animals were secondarily instilled with different bacterial species (Pseudomonas aeruginosa, Escherichia coli, or Staphylococcus aureus). Bacterial phagocytosis by alveolar macrophages was evaluated in the presence of interferon-gamma, the main cytokine produced during fungal colonization. The effect of antifungal treatments on fungal colonization and its immune response were assessed. The prevalence of P. aeruginosa pneumonia was compared in antifungal treated and control colonized rats. MEASUREMENTS AND MAIN RESULTS: C. albicans was slowly cleared and induced a Th1-Th17 immune response with very high interferon-gamma concentrations. Airway fungal colonization favored the development of bacterial pneumonia. Interferon-gamma was able to inhibit the phagocytosis of unopsonized bacteria by alveolar macrophages. Antifungal treatment decreased airway fungal colonization, lung interferon-gamma levels and, consequently, the prevalence of subsequent bacterial pneumonia. CONCLUSIONS: C. albicans airway colonization elicited a Th1-Th17 immune response that favored the development of bacterial pneumonia via the inhibition of bacterial phagocytosis by alveolar macrophages. Antifungal treatment decreased the risk of bacterial pneumonia in colonized rats.

CD89 Is a Potent Innate Receptor for Bacteria and Mediates Host Protection from Sepsis.

Direct bacterial recognition by innate receptors is crucial for bacterial clearance. Here, we show that the IgA receptor CD89 is a major innate receptor that directly binds bacteria independently of its cognate ligands IgA and c-reactive protein (CRP). This binding is only partially inhibited by serum IgA and induces bacterial phagocytosis by CD11c+ dendritic cells and monocytes and/or macrophages, suggesting a physiological role in innate host defense. Blood phagocytes from common variable immunodeficiency patients bind, internalize, and kill bacteria in a CD89-dependent manner, confirming the IgA independence of this mechanism. In vivo, CD89 transgenic mice are protected in two different models of sepsis: a model of pneumonia and the cecal ligation and puncture (CLP) polymicrobial model of infection. These data identify CD89 as a first-line innate receptor for bacterial clearance before adaptive responses can be mounted. Fc receptors may emerge as a class of innate receptors for various bacteria with pleiotropic roles.