Salmonella enterica is an intracellular pathogen that colonizes many different host cell types in vivo, including macrophages and epithelial cells. We have shown that Salmonella enterica resides within two distinct compartments in epithelial cells, confined to a membrane-bound vacuole known as the Salmonella-containing vacuole (SCV) and also freely within the cytosol. A subpopulation of internalized bacteria lyse their nascent SCV, leading to bacterial hyper-replication in the epithelial cytosol, transcriptional reprogramming and eventual egress into the gut lumen, providing a potential mechanism of bacterial dissemination. Our research is aimed towards addressing the following outstanding questions: (1) Why do only some Salmonella lyse their vacuole? (2) How does Salmonella lyse its vacuole? and (3) How does Salmonella adapt and survive in the host cell cytosol?
Our lab is currently developing a vaccine against BK polyomavirus (BKV). We’ve recently found that BKV hijacks a cellular mutagenic enzyme, APOBEC3B, to acquire targeted mutations that allow the virus to escape from neutralizing antibodies. A likely side effect of this “judo” move, in which the virus turns a host defense mechanism to its advantage, is potentially carcinogenic damage to the host cell. Separate epidemiological studies and cancer genomics surveys have recently converged on the conclusion that BKV causes at least a small fraction of bladder cancers, particularly in kidney transplant patients.