Klebsiella Pneumoniae Pathogenesis in Immunocompetent and Immunosuppressed Hosts

Type of Award: Catalyst
Date Awarded: August 2014
Award End Date: July 2016
Amount Awarded: $ 200,000.00
PI(s): Mark Mandel, PhD, NU; Nancy Freitag, PhD, UIC;

Abstract: Hospital-acquired bacterial infections are an insidious public health threat. In recent years patient deaths have been linked to a new class of superbugs, Carbapenem-resistant Enterobacteriaceae (CRE), which are primarily Klebsiella pneumoniae (Kpn) and Escherichia coli bacteria (1). There has been a pronounced alarm about the rising threats posed by these bacteria; PBS Frontline has called them "Nightmare Bacteria" and the NY Times announced "Deadly Bacteria That Resist Strongest Drugs Are Spreading". The Centers for Disease Control and Prevention (CDC) has labeled CRE bacteria as one of the top threats to public health (1). Unfortunately, they are resistant to modern antibiotics. This proposal applies proven modern genetic approaches to discover which bacterial genes and proteins are required to cause these lethal infections. It further explores whether propofol, the most commonly-used anesthetic drug for surgeries and intubation, increases patient susceptibility to CRE infection. Together, these studies will lead to a greater understanding of hospital-acquired CRE infections as well as the identification of Kpn proteins that can be targeted for novel therapies to eliminate hospital-based transmission of this deadly pathogen. This proposal addresses new complementary avenues of investigation for both the Mandel and Freitag Laboratories.