Abstract
The facultative intracellular pathogen Salmonella enterica Typhimurium (STM) resides in a specific membrane-bound compartment termed the Salmonella-containing vacuole (SCV). STM is able to obtain all nutrients required for rapid proliferation, although being separated from direct access to host cell metabolites. The formation of specific tubular membrane compartments, called Salmonella-induced filaments (SIFs) are known to provides bacterial nutrition by giving STM access to endocytosed material and enabling proliferation. Additionally, STM expresses a range of nutrient uptake system for growth in nutrient limited environments to overcome the nutrition depletion inside the host. By utilizing dual fluorescence reporters, we shed light on the nutritional environment of intracellular STM in various host cells and distinct intracellular niches. We showed that STM uses nutrients of the host cell and adapts uniquely to the different nutrient conditions. In addition, we provide further evidence for improved nutrient supply by SIF formation or presence in the cytosol of epithelial cells, and the correlation of nutrient supply to bacterial proliferation.
Highlights
Salmonella enterica is an invasive, facultative intracellular pathogen causing diseases ranging from gastroenteritis to systemic typhoid fever
Epithelial cells and macrophages were infected with serovar Typhimurium (STM) containing the dual fluorescence reporters, lysed and intracellular released bacteria measured by flow cytometry (FC)
We demonstrated that biotin is only synthesized by STM if biotin is limiting in the Salmonella-containing vacuole (SCV) or cytosol, otherwise it is retrieved from the host
Summary
Salmonella enterica is an invasive, facultative intracellular pathogen causing diseases ranging from gastroenteritis to systemic typhoid fever. With 93.8 million foodborne diseases and 155,000 deaths per year, Salmonella is a major public health problem (Majowicz et al, 2010). Salmonella infections are life-threatening and require appropriate and effective antibiotic therapy. The development of multidrug-resistant Salmonella serotypes has a major impact on the effectiveness of antibiotic therapy, new anti-infective strategies are required (Eng et al, 2015). Essential for intravacuolar survival is the function of the type III secretion system (T3SS) encoded by genes on Salmonella pathogenicity island 2 (SPI2) (Hensel et al, 1998). The SPI2-T3SS translocates a set of effector proteins across the Nutritional Environment of Intracellular Salmonella
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