4th Joint Call: TIC-TAC
The current antibiotic crisis represents a global problem of fundamental importance, comparable with other global challenges as e.g. climate change or sustainable energetics, but far less discussed in the society. Without active approach right now the, the infectious diseases will soon become the most frequent cause of death worldwide.
The TIC-TAC project consists of two objectives aiming to avert the threat of an antibiotic crisis: 1) Knowledge-based hunt for novel bioactive metabolites derived from plants and microorganisms and 2) Development of promising compounds into drugs.
Within the Objective 1 we will create a collection of 1000+ unique Actinobacteria strains, a corresponding number of culture broth crude extracts, and 100+ plant crude extracts. Metabolites in the crude extracts will be separated into 5000+ fractions and these will be tested for a broad spectrum of biological activities, particularly against clinically important pathogenic microorganisms (including MDR strains). These include Mycobacterium tuberculosis (causing tuberculosis), G- bacteria, Plasmodium falciparum (causing malaria), Zika virus, and others.
The Objective 2 aims to the development of previously patented hybrid lincosamide derivatives developed by the Czech team and further compounds suggested by SEA teams into drugs.
Our strategy to combat the antibiotic (antibacterial and antiparasitic) crisis exploits natural products that proved to be a superior source of druggable compounds. We will use modern biology and chemistry methodology for this purpose – knowledge-based genome mining (oriented on the search for biosynthetic pathways utilizing alkyl-proline derivatives, which are far more efficient when compared to L-proline incorporating compounds), mass spectrometry-based metabolomics (GNPS molecular networking + other bioinformatics tools); and we will focus on testing multiple targets, i.e. multiple pathogens including those clinically most important and threatening. CZ team will provide a collection of the clinically most dangerous bacterial strains from the WHO list for antimicrobial activity testing; Thai team possess a collection of P. falciparum strains for antimalarial properties and resistant M. tuberculosis strains for antimicrobial properties testing. Unique sources of bioactive metabolites from yet underexplored Thai and Indonesian biotopes will be used to search for new compounds.
Institute of Microbiology, Czech Academy of Sciences, Czech Republic (PI and main coordinator - Jiri Janata)
School of Pharmacy, Walailak University, Thailand (PI and coordinator for SEA - Amit Jaisi)
Faculty of Pharmacy, Andalas University, West Sumatra, Indonesia (Deri Dachriyanus)
Research Centre for Chemistry, Indonesian Institute of Science (LIPI), Indonesia (Abdi Wira Septama)
Jiri Janata, Ph.D.