Welcome to the Rosen lab!

Graphic of human body highlighting anatomical sites of documented Kp infection.
Anatomical sites of documented Kp infection
(Ferrer et al., 2021)

Our lab focuses on the pathogenesis of Klebsiella pneumoniae (Kp) — an opportunistic pathogen that is increasingly becoming multidrug resistant. As a result, resistant Kp is deemed “urgent” by the CDC and a “priority pathogen” by the World Health Organization.

Kp can be characterized as classical, which primarily causes nosocomial infections, or hypervirulent, which can infect healthy hosts. Vaccine development is challenging within this species as it has over 80 known capsular types and at least eight different O-antigens. In addition to these virulence factors, our lab is interested in the type 1 pilus operon and, specifically, the fimK regulatory gene that is unique to Kp.

Our lab predominantly works with classical isolates, such as TOP52, which allows us to utilize mouse models of pneumonia and urinary tract infection to study its pathogenesis and the subsequent host immune response. Our lab, also, studies hypervirulent strains — most notable 43816 and NTUH — and a repository of strains (over 300) collected from various sites within human patients.

Split graphic highlighting the differences between classical versus hypervirulent Kp and virulence factors of interest.
Classical versus hypervirulent Kp and virulence factors of interest

While antibiotics are not successful in killing this pathogen, our lab is striving to develop methods to inhibit the virulence of this organism or prevent infection through the development of vaccines.

Principal Investigator

David Rosen, MD, PhD

David Rosen, MD, PhD, evaluates children in the Infectious Diseases service at St. Louis Children’s Hospital. In the research lab, he studies basic pathogenic mechanisms of Klebsiella pneumoniae. This organism often carries sets of genes that render it resistant to most, if not all, antibiotics available. Klebsiella, and other carbapenem-resistant Enterobacteriaceae (CRE), have recently been assigned a threat level of urgent by the CDC. Utilizing mouse models of pneumonia and urinary tract infection, Rosen dissects mechanisms by which Klebsiella pneumoniae infects the host. Specific interests includes differential regulation of virulence determinants, including type 1 pili and capsule, and adaptive immune responses to Klebsiella in the lung. The ultimate goal is to develop further understanding of Klebsiella pneumoniae pathogenesis, which may reveal alternative therapies to combat these resistant organisms.