Virulence of Burkholderia cepacia complex strains in gp91phox-/- mice

Abstract

In cystic fibrosis (CF), infection with Burkholderia cepacia complex (Bcc) strains may cause long-term asymptomatic airway colonization, or severe lung infection leading to rapid pulmonary decline. To assess the virulence of Bcc strains, we established a lung infection model in mice with a null allele of the gene involved in X-linked chronic granulomatous disease (CGD). CGD mice, challenged intratracheally with 10(3) cells of the epidemic Burkholderia cenocepacia strain J2315, died within 3 days from sepsis after bacteria had multiplied to 3.3 x 10(8) cells. Infected mice developed neutrophil-dominated lung abscesses. Other B. cenocepacia strains and a B. cepacia strain were less virulent and one B. multivorans and one B. vietnamensis CF isolate were both avirulent. Bcc mutants, defective in exopolysaccharide synthesis or quorum sensing revealed diminished or no abscess formation and mortality. Immunofluorescence staining of Bcc-infected murine and CF lung tissues revealed colocalization of Bcc and neutrophils, suggesting Bcc persistence within neutrophils in CGD and CF. In vitro, Bcc cells were rapidly killed during aerobic neutrophil phagocytosis; however, the pathogens survived in neutrophils with blocked nicotinamide adenine dinucleotide phosphate oxidase activity and under anaerobic conditions. We conclude that the Bcc infection model in CGD mice is well suited for the assessment of Bcc virulence.