Klebsiella pneumoniae is a bacterium that causes pneumonia, urinary tract infection, and bloodstream infection. Klebsiella is one of the most common hospital-acquired respiratory infections in children and is associated with high mortality. The organism’s polysaccharide capsule and thread-like organelles (fimbriae) that extend beyond the capsule contribute to its extensive abilities to resist antibiotic treatment. New ways to fight this organism are desperately needed. To uncover the molecular mechanisms by which Klebsiella pneumoniae causes disease, this project will study a preclinical murine model of pneumonia that mimics human infection.
Proposed specific aims
· Determine the mechanisms by which Klebsiella pneumonia regulate fimbriae and capsule production to cause severe lung infection.
· Determine how the bacterial signaling molecule cyclic di-GMP influences Klebsiella capsule and fimbriae to increase,pulmonary virulence.
· Characterize how Klebsiella and its capsule influence protective immunity to respiratory tract infection.
Potential impact on child health
Uncovering the molecular mechanisms of Klebsiella pneumonia’s virulence can lead to development of new therapies or vaccine candidates to combat or prevent Klebsiella infections in at-risk populations, including infant and hospitalized pediatric populations.