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报告题目: Investigate mechanisms of resistance of antimycobacterial compounds and assess their synergy with antibiotics
报告单位人: Institute of Pasteur in France
报告人:Professor Brigitte Gicquel
地点:实验18楼302室
时间:2018-1-30 10:00-11:30
主持人: 张立新研究员
简历: Professor Brigitte Gicquel is a Professor at Institut Pasteur, Head of the Mycobacterial Genetics Unit and head of the joint laboratory Pasteur-Nanshan CCD with Shengyuan Liu as a Co-head. She will be an employee of the Nanshan CCDC starting January 2018 although she will be acting Principal investigator of the joint laboratory Pasteur-Nanshan CCDC by the end of the year 2017.
She has a State doctoral thesis in Biological sciences from the Paris 7 University, a Ph.D. thesis in Biological Sciences from Paris 7 University and a Master of Biological Sciences from the same university.
Pr. Brigitte Gicquel’s team has developed molecular genetics tools for the study of microbial virulence, new diagnostic tests and molecular epidemiology. They have recently started the search for new antibacterials associated with nanoparticles in collaboration with Dr. Jesus de la Fuente within the NAREB FP7 projects she is coordinating until August 2018.
Brigitte Giccquel has been a Chinese Academy of Science (CAS) visiting professor and a PI at the Institut Pasteur of Shanghai since 2012. She has been collaborating with Pr. Qian GAO at FUDAN University and Pr Jian MEI at the Shanghai CDC, thus publishing more than 10 papers in peer reviewed journals issued from Chinese collaborations. She is a member of SAFEA the foreign expert office of the Chinese government. She is a member of the French Healthcare Alliance in China.
报告摘要
Tuberculosis remains an important cause of morbidity and mortality throughout the world, amplified by the expansion of antibiotic resistance. This problem points at an urgent need for novel compounds with antimycobacterial properties and improving existing therapies.
One of the research interests of our laboratory is to increase the portfolio of molecules with anti-mycobacterial activity thanks to the new concept of parallel screening with different mycobacterial species (M. aurum, M. marinum). The screening used synthesized small molecules provided by the CNCL (Chinese national Compound Library) as well as natural compounds. For the most promising compounds with antimycobacterial activity, the next step was to investigate their mechanisms of resistance, and assess their synergy with antibiotics.
Among these molecules, we found that the ionophore enhanced beta-lactam activity in M. tuberculosis infected macrophage. Furthermore, resistance mechanism to ionophores is mediated by the MmpL5-MmpS5 transporter. We have shown that the upregulation of MmpL5 can lead to resistance of ionophores. Another study showed that the efflux-pump MmpL5 is also a non-target-based resistance to bedaquiline, the first new anti-TB drug approved in 40 years. This presentation should provide an update on the role of these pumps in antibiotic resistance in Mycobacterium. The use of efflux pump inhibitors as adjuvant therapy should be considered for clinical treatment of tuberculosis.