Evaluation of the inhibitory activity of analogs of the antimicrobial peptide B1CTcu5 in portuguese clinical isolates of extensively drug-resistant Mycobacterium tuberculosis and investigation of the mechanism of action

• Grant number: 23/16711-5
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Start date: May 17, 2024
• End date: August 16, 2024
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Fernando Rogério Pavan
• Grantee: Laura Maria Duran Gleriani Primo
• Supervisor: Joao Ruben Lucas Mota Perdigao
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Institution abroad: Faculdade De Farmácia Da Universidade De Lisboa, Portugal
• Associated to the scholarship: 23/10440-0 - Evaluation of the in vitro activity of B1CTcu5 peptide analogues in macrophages infected with Mycobacterium tuberculosis., BP.IC

Abstract

Mycobacterium tuberculosis (MTB) is the main etiological agent of tuberculosis, one of the top infectious killers in the world. The World Health Organization (WHO) estimated that this millennium-old bacillus infects about one quarter of the global population. Additionally, with poor treatment and drugs, multidrug resistant strains of M. tuberculosis (MDR-TB) have emerged and cause a public health crisis. Antimicrobial peptides (AMPs) are promising compounds to the treatment of drug resistant bacterias, such as MDR-TB. Our research team had developed and synthesized 3 analogues of B1CTcu5, a natural AMP, that have significant activity against MTB and a brazilian clinical isolate (MDR-TB). Also those antimicrobial peptides are not cytotoxic in human lung fibroblasts. However, to a better elucidation of their activity and selectivity index it is necessary more studies, with other MDR-TB strains, different cell types and a whole-genome sequencing (WGS) of spontaneous resistant mutants. Professor João Perdigão has a portuguese clinical isolates MDR-TB library and cell lineages of the MTB-model, through which the activity of these AMPs can be deeply evaluated. Therefore this project has as an objective to evaluate the anti-resistant Mycobacterium tuberculosis activity of analogues of antimicrobial peptide B1CTcu5, determine their cytotoxicity in THP-1 and A549 and investigate the primary genetic response of MTB against the AMPs. In the aim of elucidating a therapeutic strategy against multidrug resistant M. tuberculosis.