Forschungs- & Entwicklungsinformationsdienst der Gemeinschaft - CORDIS


PATHOPROT Berichtzusammenfassung

Project ID: 309831
Gefördert unter: FP7-IDEAS-ERC
Land: Sweden

Mid-Term Report Summary - PATHOPROT (In vivo pathogen proteome profiling using selected reaction monitoring)

Bacterial infections represent a major and global health problem, which is further aggravated by the rapid and ongoing increase in antibiotic resistance. The limited success in the development of targeted therapies for particular invasive strains can be attributed to our limited knowledge how pathogens modulate their proteome homeostasis in vivo, knowledge that has so far remained elusive due to technical limitations.
Here I propose the use of proteome-wide selected reaction monitoring mass spectrometry (SRM-MS) for pathogen proteome profiling from samples obtained directly from in vivo using group A streptococci (GAS) as a model system. GAS is a common colonizer of the skin and the upper respiratory tract where it causes relatively mild clinical conditions such as impetigo and pharyngitis, but GAS can also penetrate into deeper tissues and cause severe and potentially life-threatening conditions such as necrotizing fasciitis and sepsis. This proposal describes the use of SRM-MS to facilitate the construction of comprehensive and quantitative molecular anatomy knowledge models outlining spatial organisation, pathway organization, absolute protein concentration estimations and interaction partners with host for complete microbial proteomes. Using the molecular anatomy as benchmark I intend compare how the proteome homeostasis is controlled in pathogens isolated directly from patients with different degree of disease severity to understand how disease severity, anatomical location and host dependencies effects the proteome homeostasis.
The outlined proposal describes a generic strategy to provide comprehensive understanding of the pathogen adaption directly in vivo and represents a paradigm shift in the field of bacterial infectious disease. This proposal, will due to the high level of interdisciplinary components, enlighten central aspects within the medical microbiology field that has been long sought for but never studied due to technology limitations. The anticipated data from this project will be groundbreaking and worldwide unique and will fuel research for the coming years, in particular the development of the next generation targeted vaccine and therapeutic development programs.

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