Talare: Tone Tønjum, Oslo University Hospital, Norway
Denna föreläsning anordnas av Umeå Centre for Microbial Research, UCMR. Värd: Fredrik Almqvist, UCMR
Om föreläsningen:
Mycobacterium tuberculosis (Mtb) is the intracellular causative agent of tuberculosis (TB), one of the top 10 causes of death worldwide and the leading cause of death from infectious disease. This bacterium is inhaled in aerosol droplets and once in the lung, it is engulfed by alveolar macrophages. Inside the activated macrophage, Mtb is exposed to a hostile environment, including reactive oxygen species (ROS) and reactive nitrogen species (RNS) that cause oxidation, deamination and alkylation of macromolecules. This toxic environment is fatal to most pathogens, but Mtb has the ability to sense the host environment and eventually enter into a non-replicating, persistent state. Mtb cells can remain in this latent stage for a long time without causing disease or, under certain conditions, it can awake resulting in active TB disease. We have characterized the unique nature of the relatively static Mtb genome, as well as DNA instability and repair as a basis for its survival. We have also delineated the vivid Mtb transcriptional landscape, and characterized small non-coding RNAs transcribed under genotoxic stress as well as during reactivation from dormancy. Among the regulatory mechanisms that contribute to the complexity of the genomes and proteomes of Mtb, are macromolecular decorations such as post-translational modifications (PTMs) of peptides. PTMs allow bacteria to rapidly alter protein activity in response to host factors and have been implicated in Mtb virulence and antimicrobial resistance (AMR). The global acetylome and glycoproteomic profile of different Mtb lineages unveil the role of these PTMs in mycobacterial adaptation, survival and AMR. Understanding the genome dynamics of Mtb enables developing effective treatment and diagnostic tools, as well as managing the increasing numbers of drug-resistant TB strains. Examples of new potential therapy targeting Mtb DNA will be presented.
Integrated Biomedical Science Seminars: är en en bred, öppen seminarieserie inom life science som arrangeras gemensamt.