Cell-type-specific hypertranslocation of effectors by the Pseudomonas aeruginosa type III secretion system.

Many Gram-negative pathogens use a type III secretion system (T3SS) to promote disease by injecting effector proteins into host cells. Common to many T3SSs is that injection of effector proteins is feedback inhibited. The mechanism of feedback inhibition and its role in pathogenesis are unclear. In the case of P. aeruginosa, the effector protein ExoS is central to limiting effector injection. ExoS is bifunctional, with an amino-terminal RhoGAP and a carboxy-terminal ADP-ribosyltransferase domain. We demonstrate that both domains are required to fully feedback inhibit effector injection. The RhoGAP-, but not the ADP-ribosyltransferase domain of the related effector protein ExoT also participates. Feedback inhibition does not involve translocator insertion nor pore-formation. Instead, feedback inhibition is due, in part, to a loss of the activating trigger for effector injection, and likely also decreased translocon stability. Surprisingly, feedback inhibition is abrogated in phagocytic cells. The lack of feedback inhibition in these cells requires phagocytic uptake of the bacteria, but cannot be explained through acidification of the phagosome or calcium limitation. Given that phagocytes are crucial for controlling P. aeruginosa infections, our data suggest that feedback inhibition allows P. aeruginosa to direct its effector arsenal against the cell types most damaging to its survival.

Near Peer Mentors to Address Socio-Emotional Issues Among Underrepresented Minority High School Students in Research Intensive STEM Programs: Perceptions of Students and Mentors.

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.