Papers by Cynthia Ivonne Droguett Castillo
Infection and Immunity, 2006
ABSTRACTYersinia pseudotuberculosisinfects many mammals and birds including humans, livestock, an... more ABSTRACTYersinia pseudotuberculosisinfects many mammals and birds including humans, livestock, and wild rodents and can be recovered from the lungs of infected animals. To determine theY. pseudotuberculosisfactors important for growth during lung infection, we developed an intranasal model of infection in mice. Following intranasal inoculation, we monitored both bacterial growth in lungs and dissemination to systemic tissues. Intranasal inoculation with as few as 18 CFU ofY. pseudotuberculosiscaused a lethal lung infection in some mice. Over the course of 7 days, wild-typeY. pseudotuberculosisreplicated to nearly 1 × 108CFU/g of lung in BALB/c mice, induced histopathology in lungs consistent with pneumonia, but disseminated sporadically to other tissues. In contrast, a ΔyopBdeletion strain was attenuated in this model, indicating that translocation ofYersiniaouter proteins (Yops) is essential for virulence. Additionally, a ΔyopHnull mutant failed to grow to wild-type levels by 4 day...
Infection and Immunity, 2010
LcrF (VirF), a transcription factor in the multiple adaptational response (MAR) family, regulates... more LcrF (VirF), a transcription factor in the multiple adaptational response (MAR) family, regulates expression of the Yersinia type III secretion system (T3SS). Yersinia pseudotuberculosis lcrF -null mutants showed attenuated virulence in tissue culture and animal models of infection. Targeting of LcrF offers a novel, antivirulence strategy for preventing Yersinia infection. A small molecule library was screened for inhibition of LcrF-DNA binding in an in vitro assay. All of the compounds lacked intrinsic antibacterial activity and did not demonstrate toxicity against mammalian cells. A subset of these compounds inhibited T3SS-dependent cytotoxicity of Y. pseudotuberculosis toward macrophages in vitro . In a murine model of Y. pseudotuberculosis pneumonia, two compounds significantly reduced the bacterial burden in the lungs and afforded a dramatic survival advantage. The MAR family of transcription factors is well conserved, with members playing central roles in pathogenesis across b...
Cellular Microbiology, 2010
Type III secretion systems deliver effector proteins from gram-negative bacterial pathogens into ... more Type III secretion systems deliver effector proteins from gram-negative bacterial pathogens into host cells, where they disarm host defenses, allowing the pathogens to establish infection. Although Yersinia pseudotuberculosis delivers its effector proteins, called Yops, into numerous cell types grown in culture, we show that during infection Y. pseudotuberculosis selectively targets Yops to professional phagocytes in Peyer's patches, mesenteric lymph nodes and spleen, although it co-localizes with B and T cells as well as professional phagocytes. Strikingly, in the absence of neutrophils, the number of cells with translocated Yops was significantly reduced although the bacterial loads were similar, indicating that Y. pseudotuberculosis did not arbitrarily deliver Yops to the available cells. Using isolated splenocytes, selective binding and selective targeting to professional phagocytes when bacteria were limiting was also observed, indicating that tissue architecture was not required for the tropism for professional phagocytes. In isolated splenocytes, YadA and Invasin increased the number of all cells types with translocated Yops, but professional phagocytes were still preferentially translocated with Yops in the absence of these adhesins. Together these results indicate that Y. pseudotuberculosis discriminates among cells it encounters during infection and selectively delivers Yops to phagocytes while refraining from translocation to other cell types.
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Papers by Cynthia Ivonne Droguett Castillo