HUVASC-SEQ · Functional Genomics Analysis of Neisseria meningitidis interactions with human dermal blood vessels in vivo
7РП — „Хора“ (Действия „Мария Кюри“)
- Период
- 2014-06-01 → 2016-05-31
- Финансиране от ЕС
- 194 047 €
- Участници
- 1
- Схема
- MC-IEF
Линиите свързват координатора с партньорите.
Накратко на български
Бактериите Neisseria meningitidis и начинът, по който те атакуват кръвните съдове в кожата, се анализират чрез специален модел с мишки. Това помага за по-доброто разбиране на механизмите, чрез които се развива менингококовата болест и се появяват кожните увреждания.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Functional Genomics Analysis of Neisseria meningitidis interactions with human dermal blood vessels in vivo
Until recently the use of animal models to study N. meningitidis infection did not accurately reproduce the key features of meningococcal disease. Previous models only permitted the study of prolongation of bacteremia in time, but without showing the development of skin lesions, petechial rashes and purpura. The recent development of the “humanized mouse model” (hMM) for meningococcal infection at the host lab, reproduces the skin and purpuric lesions seen during meningococcal septic shock (Melican et al., 2013). The hMM introduces human functional dermal micro-vessels by xenografting human skin onto immunodeficient mice (Melican et al., 2013). N. meningitidis injected into the blood circulation migrates to and adheres specifically to the human endothelium present in the skin graft. At the endothelium site N. meningitidis establishes micro-colonies, proliferates and fills the lumen of the vessels in a process that is referred to as “vascular colonization” (Melican and Dumenil, 2012; Melican et al., 2013). The vascular colonization leads to an inflammatory response, tissue damage and formation of purpuric lesions (Melican et al., 2013) mimicking what is seen in humans in acute meningococcemia. Importantly, the vascular colonization process is mediated and dependent on the Type IV pili structure (Melican et al., 2013). The present project proposed the use of the hMM and the application of studies at genome-wide scale (High throuput Insertion Tracks Sequencing and RNA-seq analysis) and functional assays to gain a better understanding of the mechanisms of vascular colonization and meningococcal disease in vivo. The present project has allowed us to identify new gene candidates important for virulence during the process of vascular colonization. This study is providing new insights in the N. meningitidis pathogenesis and give the potential to develop new therapeutics.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Neisseria meningitidis is still the major cause of bacterial meningitis and septicemia worldwide. The septic shock caused by Neisserial invasive disease is characterized by the presence of skin lesions (petecchial rashes and purpura). Despite the strong association of meningococcal disease and purpura as well as the serious prognosis associated with it, the bacterial factors and physiological processes underlying these events at molecular and cellular level are still largely undescribed.Here we propose to use a recently developed humanized-mouse model of meningococcal purpura to study by functional genomics (Transcriptome analysis and gene fitness analysis by High-throuput insertion track sequencing, HITS) the host-bacteria interactions during the process of vascular colonization by N.meningitidis in vivo. We expect that combination of these two approaches would highlight bacterial and host mechanisms important for vascular colonization. By the combination of cellular and biochemical approaches we expect to dissect these mechanisms and elicit bacterial determinants used to colonize and proliferate in human blood vessels and host molecular mechanisms that participates in causing vascular damage and purpura fulminans in response to bacterial infection. Understanding the details of vascular leakage may also give indications as to how N. meningitidis are able to cross the Blood Brain Barrier and cause meningitis.This experimental approach could have the potential to highlight suitable targets for future innovative meningococcal therapeutics and vaccines development. Futhermore, this project will give to the fellow the opportunity to learn scientific, technical and complementary skills, which could support his career development to become an independent researcher in the field of host-pathogen interactions.
Оригинален текст от CORDIS (на английски).
Участници
- INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE · ParisКоординаторФранция
Връзки
Данни: CORDIS, © Европейски съюз