Commensal microorganisms influence a variety of host functions in the gut, including immune response, glucose homeostasis, metabolic pathways and oxidative stress, among others. This study describes how Salmonella Typhi, the pathogen responsible for typhoid fever, uses similar strategies to escape immune defense responses and survive within its human host. To elucidate the early mechanisms of typhoid fever, we performed studies using healthy human intestinal tissue samples and “mini-guts,” organoids grown from intestinal tissue taken from biopsy specimens. We analyzed gene expression changes in human intestinal specimens and bacterial cells both separately and after colonization. Our results showed mechanistic strategies that S. Typhi uses to rearrange the cellular machinery of the host cytoskeleton to successfully invade the intestinal epithelium, promote polarized cytokine release and evade immune system activation by downregulating genes involved in antigen sampling and presentation during infection. This work adds novel information regarding S. Typhi infection pathogenesis in humans, by replicating work shown in traditional cell models, and providing new data that can be applied to future vaccine development strategies.

In this study we have analyzed metal-enhanced fluorescence (MEF) effects from different density silver island films (SiFs) and the effects of sample geometry on the observed enhancement of fluorescence (EF). It is shown that silver islands grow exponentially with SiF deposition time (DT<7min), optical density of SiFs almost linearly depends on DT; electrical conductivity is zero. At DT>7 min, silver islands merge, exhibiting a sharp increase in electrical conductivity. It has been shown that the newly proposed SiF-Glass sample geometry exhibits higher EF values than the commonly used in MEF studies SiF-SiF sample geometry. The SiF-Glass geometry demonstrates high sensitivity for surface immunoassays, a growing application of metal-enhanced fluorescence.