Understanding Klebsiella pneumoniae respiratory infections
Date du début: 1 sept. 2013,
Date de fin: 31 août 2017
"Pneumonia is leading cause of death from infection. During infection, microbial presence is monitored by receptors recognizing evolutionary conserved structures. Pathogen recognition is associated with the activation of few regulators and signaling pathways controlling host defence systems. A better understanding of the host-pathogen interaction offers the potential for pharmacological intervention by targeting the host side.U-KARE aims to gain a holistic understanding of the networks conveying the cross-talk beteen the human pathogen Klebsiella pneumoniae (KP) and the innate immune system. KP is one of the most frequent antibiotic-resistant bacteria isolated in hospitals and the community. KP represents a paradigm of an emerging pathogen, and therefore it is both urgent and necesary to better understand its pathophysiology. My laboratory has demosntrated that KP subverts the activation of host defence processes (receptor-mediated KP recognition, and NF-kB activation) to survive in the lung. These findings lead us to hypothesize that ""the capacity of KP to survive in the lung correlates with the pathogen ability to modulate innate immune responses in its own benefit"".Critical questions that will pursued are: (i) which are KP strategies to take control over host post-transcriptional modifications; (ii) how does KP manipulate IFN-dependent pathways; (iii) how does KP manipulate cell death pathways; (iv) how does KP avoid autophagy; and (v) how does the host affect KP transcriptome.By a multidisciplinary approach encompassing microbiology, cell biology, functional genomics and immunology, U-KARE will expand our current understanding of the strategies used by KP to survive in the lung. On top of this, U-KARE will explore some of the most novel and fundamental topics in the infection biology which could lead to the identification of novel therapies based on modulating the host-pathogen interaction."
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