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Title: Klebsiella pneumoniae activates mTORC1 to control host defence responses
Author: Yoba, Sylviane
ISNI:       0000 0004 6351 2476
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2016
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Klebsiella pneumoniae is a worldwide concern as it is resistant to most antibiotics. It causes a wide range of pathologies like pneumonia, urinary-tract diseases, community-acquired and nosocomial infections. K.pneumoniae has been shown to prevent the fusion between the phagosome and the lysosome in macrophages in a PI3K/AKT-dependent manner (Cano et al., 2015). We then, postulated that it could activate the kinase mammalian target of rapamycin complex 1 (mTORCl) located downstream PI3K/AKT. mTORCl is involved in multiple cellular processes like the growth, biogenesis and the inhibition of autophagy. We demonstrated that K. pneumoniae, by activating mTORCl, inhibits autophagy, thus, promoting its survival. Moreover, K. pneumoniae controls the levels of cytokines IL-12 and IL-10 in a mTORCl and GSK3p-dependent manner. In addition, during K. pneumoniae infection, levels of IkBα are maintained in a mTORCI-dependent manner. Inflammation is also limited during the infection, through the nuclear translocation of Nrf2 and the activation of an antioxydant, HO1. The pathways TLR4-MyD88/MAL, TLR4-TRAM/TRIF, STING, PI3K/AKT/ERK and FAK are involved in the activation of mTORCl during K. pneumoniae infection. Activation of TRAM/TRIF and STING results in production of type 1 IFN, which is essential for the activation of mTORCl. K. pneumoniae activates mTORCl in a OmpA, 0 antigen, and capsule-dependent manner. Therefore, K. pneumoniae manages to manipulate the host immune system through the activation of mTORCl.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available