P114

1:Grupo Relaciones Microbianas y Epidemiológicas Aplicadas al Laboratorio Clínico y Molecular (REMA), Facultad de Ciencias de la Salud, Universidad Colegio Mayor de Cundinamarca, Bogotá, 110311, Colombia.; 2:Grupo Bioquímica y Biología Molecular de las Micobacterias (BBMM), Departamento de Química, Facultad de Ciencias, Universidad Nacional de Colombia, Bogotá, 111321, Colombia.

The emergence of multi-drug resistant (MDR) and extensively drug resistant (XDR) Mycobacterium tuberculosis strains (MTB) has driven the finding of more effective anti-tuberculosis drugs. Currently, antimicrobial peptides (AMPs) are considered interesting molecules with broad-spectrum antimicrobial activity due to their unique mode of action, which is based on their ability to bind to the cell membrane without requiring specific receptors.  In this work, we studied the antimycobacterial activity of two synthetic peptides derived from LL-37 and modified by bioinformatic tools (LL37-1 and D-LL37) against MTB, by determining the minimum inhibitory concentration; as well as the evaluation of their direct effect on membrane permeability and cell death, by fluorescence microscopy and fluorometry experiments. We found that LL37-1 peptide inhibited MTB growth from a concentration of 12.5 μM and D-LL37 peptide from 6.25 μM, with no significant cytotoxic or hemolytic activity observed at these concentrations. The direct effect of both PAMs on the bacterial cell membrane was also identified. The results obtained could significantly contribute to the pharmacological field in an attempt to promote modified PAMs in anti-tuberculosis therapies. In addition, further research can be planned to understand how MTB would respond to modified synthetic PAMs, leading to a better understanding of the mechanism of action of these molecules on bacterial virulence.

Keywords: Antimicrobial peptides (AMPs), LL-37-derived peptides, Membrane permeability, Anti-tuberculosis therapy innovation.