Fitness of Gram-negative Pathogens during Bacteremia

Seminar Details
Wednesday, October 3, 2018 - 9:00am to 10:00am


Harry Mobley, Ph.D.
Frederick G. Novy Distinguished University Professor and Chair
Department of Microbiology and Immunology
University of Michigan Medical School


5623 Med. Sci. II  (Wheeler Seminar Room)

We are losing the battle against antibiotic-resistant Gram-negative bacterial pathogens in our hospitals and clinical care facilities. The CDC estimates that over 2 million people are infected annually with 17 species of antibiotic-resistant bacterial pathogens, killing 23,000 people per year. Over half of the species are Gram-negative pathogens including carbapenem-resistant Enterobacteriaceae (CRE) and the non-fermenting opportunistic pathogen Acinetobacter baumannii. Although the CDC described carbapenem-resistant (CR) bacteria as “nightmare bacteria”, the factors required for virulence of these pathogens or their antibiotic-susceptible counterparts during bloodstream infections are largely unknown. Thus, there is an urgent need to identify unique (species-specific) and common (required by the most common six Gram-negative species) fitness and virulence factors required by these species for bacteremia, and map key metabolic pathways and essential gene sets used by these pathogens in vivo. The long-term goal of the “Healthcare-Associated Infection” component of the Host Microbiome Initiative is to delineate the mechanisms of pathogenesis in Gram-negative bacteria that cause bacteremia in our healthcare facilities. We have conducted Tn-seq and have begun to measure in vivo growth rates in representative isolates of E. coli, Klebsiella pneumoniae, Serratia marcescens, Citrobacter freundii, and Enterobacter cloacae as well as A. baumannii, in the murine model of bacteremia. Our central hypothesis is that based on the relatedness of CR species at the family (Enterobacteriaceae) and class (A. baumannii) levels, these pathogens require a combination of orthologous core functions and species-specific fitness factors to acquire nutrients and evade host responses during bacteremia. The rationale for these proposed studies is that antibiotic resistance is rising rapidly in Gram-negative pathogens that cause bloodstream infections in our health care systems. Progress to date will be reported.

Sponsored by the Host Microbiome Initiative