Projects

Several projects in our lab focus on creating approaches to detect growth differences within populations of bacteria. We plan to use these tools to determine if host-derived stresses are sufficient to the slow the growth rates of individual bacteria within host tissues, and if this impacts the antibiotic susceptibility of individual bacteria:

Antibiotic susceptibility 

We found that bacteria exposed to the antimicrobial gas, nitric oxide (NO), have reduced antibiotic susceptibility in a mouse model of Yersinia systemic infection. Reduced antibiotic susceptibility correlated with slowed bacterial growth. However, our results suggested that many additional host immune cell and bacterial pathways are impacting antibiotic efficacy. We are currently studying the pathways that dictate whether bacteria survive or are eliminated during antibiotic treatment, with a focus on studying these questions in mouse models of antibiotic treatment. Our initial experiments were completed with doxycycline treatment, and we are expanding these studies to other antibiotics, including ciprofloxacin.

Heterogeneity in virulence factor expression

Our lab utilizes fluorescent transcriptional reporters to visualize changes in bacterial gene expression during growth within host tissues.  Our previous studies have identified heterogeneity within Yersinia populations during infection, and we have recently begun utilizing Staphylococcus aureus fluorescent reporter strains constructed in collaboration with Dr. Victor Torres (NYU) to determine the spatial and temporal dynamics of S. aureus toxin expression in a mouse model of kidney abscess formation.  In addition to asking these questions in a mouse model of infection, we have also begun developing ex vivo systems to model bacterial-neutrophil interactions.

Single cell approaches 

Our lab is developing multiple single cell approaches to study bacterial heterogeneity that are complementary to our fluorescent transcriptional reporter approaches. We currently utilize flow cytometry and fluorescence microscopy to identify distinct subpopulations of cells, and are expanding into RNA-seq and RNA-FISH approaches to further characterize and identify subpopulations of bacteria that emerge within host tissues in the context of infection.