Comparative lipid profiling of a mce3 mutant of Mycobacterium tuberculosis and M. tuberculosis complex wild type strains

• Grant number: 18/18674-1
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Start date: December 15, 2018
• End date: February 28, 2019
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Ana Marcia de Sá Guimarães
• Grantee: Felipe Silva
• Supervisor: Andrea Pires dos Santos
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Purdue University, United States
• Associated to the scholarship: 17/24903-0 - Comparative analysis of mce operon gene expression levels of Mycobacterium tuberculosis during infection of human and bovine macrophages, BP.IC

Abstract

Tuberculosis (TB) is an important disease of humans and animals caused by members of the Mycobacterium tuberculosis Complex (MTBC). Members of this Complex have clonally evolved from a Mycobacterium tuberculosis ancestor and are characterized by high genomic similarity (>99% over alignable regions). Despite this relatedness, species of MTBC express different phenotypic profiles, as well as different host tropism and virulence. Mycobacterium tuberculosis, for example, is highly adapted to humans, while M. bovis has an unrestricted tropism, being able to infect and establish reservoirs in several animal species. Interestingly, the sole available vaccine to prevent TB is an attenuated strain of the generalist M. bovis (M. bovis BCG), and in addition to its well-known attenuation features, it is likely that intrinsic genetic differences between BCG strains and M. tuberculosis play an important role in defining the efficaciousness of BCG. Therefore, the evaluation of virulence features, such as the MCE (Mammalian Cell Entry) family, differently expressed among MTBC species, may help understand reasons for the differences in host tropism and virulence of the Complex. MCE operons have been linked to the transport of hydrophobic molecules and remodeling of the lipid-rich cell wall of mycobacteria. MTBC's modulation of its cell wall architecture and regulation of its biosynthesis and degradation of lipids are intimately linked to their ability to cause disease in its hosts. Thus, the aim of this study is to determine and compare the cell wall lipid profiles of a mce3A (mce3A) mutant of M. tuberculosis CDC1551 and the wild-type strains M. tuberculosis CDC1551, M. tuberculosis HR37v and M. bovis SP38, using Liquid Chromatography coupled with Mass Spectrometry analysis. This study will complement the data obtained in the Scientific Initiation Project associated with this proposal and, due to the importance of the lipids in the immune response caused by MTBC infection, it may also contribute to the understanding of the differential host tropism of MTBC members for different host species, and the development of new vaccine strategies. (AU)