Projects

Klebsiella pneumoniae Virulence Factor Regulation in the Respiratory Tract

Histology of lungs infected with wild-type
Klebsiella pneumoniae contrasted to lung infected
with a fimK mutant.

Klebsiella pneumoniae is one of the most common causes of nosocomial pneumonia and is difficult to treat given the high rate of antimicrobial resistance. We have developed mouse models of pneumonia that highly recapitulate human disease in order to study what factors are important for Klebsiella to survive in vivo. Capsule is known to be an important factor for virulence in the lung but its cues for expression are not well understood. We have found that capsule expression may be counter-regulated by the expression of type 1 pili that may be important in other environmental niches outside the lung. Ongoing studies are aimed at uncovering the mechanisms Klebsiella uses to differentially express its wide range of virulence factors in response to host conditions and cues.


Adaptive Immune Responses to Klebsiella pneumoniae Infection of the Lung

A vaccine to prevent Klebsiella pneumoniae infections could potentially save the lives of many patients already known to be colonized with resistant isolates. However, Klebsiella can mask itself in one of eighty different polysaccharide capsular coats, making it difficult to create a vaccine that would be effective against many different isolates. We are using a model of protective immunity to learn more about how the host immune system protects from repeated Klebsiella infection. Preliminary data suggest that there may be non-capsular antigens that play a role in immunity. A variety of mouse lines with defects in specific aspects of adaptive immunity are being employed to define the specific host mechanisms used to protect from Klebsiella pneumoniae infection.

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