Kimberly

M

Davis

,

PhD

It has been known for decades that bacterial populations are heterogeneous, but it has been difficult to develop therapeutics that take this into account. Individual bacteria within a population vary in their growth rates, which leads to inherent differences in antimicrobial susceptibility. Additionally, many therapeutics have been designed to target specific virulence factors, which are required for bacterial growth in host organisms. However, it remains unclear if these factors are required at specific stages of infection, and if these factors are produced by the entire bacterial population, or only subsets of bacteria. 

Our lab explores heterogeneity within bacterial populations utilizing approaches that include transcriptional fluorescent reporters to visualize bacterial gene expression at the single cell-level, and immunofluorescence microscopy to visualize heterogeneity within host cell populations.  Our overarching goals are to define the expression patterns of potential drug targets and improve understanding of the pathways that promote altered antibiotic susceptibility, to ultimately develop improved therapeutics. Recently, we have developed molecular tools to identify slow-growing subsets of Yersinia with reduced antibiotic susceptibility, and have generated an antibiotic-sensing reporter to detect tetracycline exposure within host tissues. We have shown that bacteria responding to host-derived nitric oxide are slow-growing and have reduced antibiotic susceptibility, and are currently developing single cell transcriptional approaches to further characterize subpopulations of bacteria that survive antibiotic treatment. We are also studying the role of phenotypic heterogeneity in Staphylococcus aureus abscess  formation, in both ex vivo and mouse model systems.