Effector injection inactivates the phagocytic machinery in these cells (Rangel et al., 2014) and results in an inability to produce a reactive oxygen species burst (Vareechon et al., 2017). These phenotypes are dependent on effector proteins that are injected into host cells via the T3SS. To date, four effector proteins have been described in P. aeruginosa isolates. ExoS and ExoT are highly homologous bifunctional effector proteins with an amino-terminal Rho-GTPase activating protein (RhoGAP) domain and a carboxy-terminal ADP-ribosyltransferase domain (ADPRT) (Barbieri and Sun, 2004). ExoU, is a potent phos
A Near Peer Mentoring Program (NPMP) was developed in which Medical Student Training Program(MSTP) students met weekly with small groups of high school students who were participating in an intensive summer biomedical research immersion program. The goal of the NPMP was to provide and engage the high school students with opportunities to express and discuss their research and more importantly, their stresses and concerns. After initial reservations, the NPMP provided a comfortable venue for high school students to engage in discussions of both laboratory and personal topics. Overall, their concerns and stresses were expressed in five categories: 1) College Preparation, 2) Preparation for MD and PhD Training and Careers, 3) Summer Research Programmatic Issues and Laboratory Social Structure, 4) Social Issues, and 5) Health and Wellness. High school students identified the following major factors as contributing to programmatic success: relatability, role models, comfort and approachability, organization, and mentor fit. The Near Peer Mentoring initiative revealed the need for STEM and other programs targeting academic success and career development to be alert to social and emotional concerns of students and to provide opportunities for their expression, discussion and guidance.
Type III secretion systems are integral to the pathogenesis of many Gram-negative bacterial pathogens. A hallmark of these secretion systems is that they deliver effector proteins vectorially into the targeted host cell via a translocation pore.
The type III secretion system (T3SS) is a syringe-like virulence factor which delivers bacterial proteins directly into the cytoplasm of host cells. An essential component of the system is the translocon, which creates a pore in the host cell membrane through which proteins are injected. In Pseudomonas aeruginosa, the translocation pore is formed by proteins PopB and PopD and attaches to the T3SS needle via the needle tip protein PcrV. The pore is multimeric, but the exact stoichiometry and structure of the pore are unknown. We took a genetic approach to map contact points within the system by taking advantage of the fact that the translocator proteins of Pseudomonas aeruginosa and the related Aeromonas hydrophila T3SS are incompatible and cannot be freely exchanged. We created chimeric versions of P. aeruginosa PopB and A. hydrophila AopB to intentionally disrupt and restore protein-protein interactions. We identified a chimeric B-translocator that specifically breaks an interaction with the needle tip protein and interferes with the formation of the translocation pore. Breaking the interaction did not disrupt membrane insertion, arguing that the needle tip protein chaperones formation of the translocation pore.
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