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Professor Linda Kenney is a Senior Researcher in the Mechanobiology Institute at the National University of Singapore. Her work has focused on two-component signaling in E. coli and Salmonella and she is now using super-resolution microscopy to image the infection process. She is developing heterologous host models including Zebrafish and C. elegans to understand the host-pathogen interactions involved during S. Typhimurium and S. typhi infection. Prof. Kenney was just elected as a fellow of the American Academy of Microbiology and also serves as an American Society of Microbiology Distinguished Lecturer. Dr. Kenney trained at the University of Pennsylvania and Yale and Princeton Universities. She has held faculty positions at the University of Illinois and Oregon Health and Science University.
Imaging Salmonella Infections
After ingestion of Salmonella from contaminated food or water, it transits through
the stomach and then catalyzes its uptake across the intestinal epithelium. This process requires pathogen-stimulated changes in host actin and other pathways resulting from activation of genes located on Salmonella pathogenicity island 1 (SPI-1). Salmonella subsequently trafficks across the epithelium, and is phagocytosed by macrophages, where it resides in an acidic vacuole. The Salmonella cytoplasm acidifies to pH 5.6 and this acidification step is an important signal in activating genes on pathogenicity island 2 (SPI-2). SPI-2 encodes a type three secretion system that secretes effectors that modify
the vacuole, preventing its degradation as well as endosomal tubulation. Using super- resolution imaging in single bacterial cells, we show that low pH induces expression of the SsrA/B two-component signaling system located on SPI-2. Single particle tracking identifies a pH-dependent stimulation of DNA binding by SsrB. The low level of SPI-2 injectisomes observed in single cells is not due to fluctuating SsrB levels in single cells. Super-resolution imaging enables us to visualize the emergence of Salmonella-secreted effectors into the host cytoplasm and follow the resulting endosomal tubulation. This
work highlights the surprising role that acid pH plays in the virulence and intracellular lifestyle of Salmonella, and suggests that modification of acid survival pathways represents a potential target for inhibiting Salmonella. Our studies of infection in heterologous host models allow us to visualize many steps in the entire infection process. Supported by the Research Center of Excellence in Mechanobiology from the Ministry of Education, Singapore, VA 5I01BX000372 and NIH AI123640.