Screening of antimicrobial peptides with potential to treat mycobacterial infections

SALVADORI, LUCIA; MARTINI MARÍA CARLA; DEL PAPA MARÍA FLORENCIA

Congreso; SAIB 2022; 2022

Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), is one of the first causes of death worldwide and other mycobacterial infections are increasing globally. Mycobacterium abscessus (Mab) causes pulmonary disease and is particularly deadly among cystic fibrosis and other immunocompromised patients. The failure of mycobacterial treatments is due, in part, to development and spread of drug-resistant and multidrug-resistant strains, for which the available antibiotics are poorly or not at all efficient, in addition to produce severe side effects in patients. Despite of the exhaustive research in the academic and private sector, only a few compounds have been proved to be efficient against mycobacteria and safe for humans, highlighting the need for expanding the horizons to less conventional or less explored compounds. Such is the case of antimicrobial peptides (AMPs), a diverse class of short peptides, usually between 10 and 60 amino acids long and a net positive charge, produced as a first defense line by a variety of organisms, ranging from procaryotesprokaryotes to humans. Here we focus on the screening of AMPs with antimycobacterial activity produced by soil bacteria. We developed a modified version of the traditional supernatant-agar method for selecting those bacteria capable of inhibiting mycobacterial growth. We screened over a hundred isolates from three diverse bacterial collections previously established in our lab. A total of 12 and 5 strains displayed promising growth-inhibition activity against the non-pathogenic and fast-growing bacterium M. smegmatis (Msm, a model mycobacterial organism) and Mab, respectively. The bacteria displaying inhibition against mycobacteria belong to the genus genera Terribacillus, Staphylococcus, Curtobacterium, Microbacterium, Pseudomonas, Paenibacillus, Serratia, and Pantoea, most of which have not been reported to produce antimycobacterial compounds. Those isolates that exhibited inhibition against Msm or Mab are currently being assayed against Mtb. Overall, our results show several promising isolates secreting toxic compounds for mycobacteria and point out the soil as an important reservoir of bacteria-producing natural compounds with potential to treat mycobacterial infections. Future studies are needed to establish the mechanistic of growth-inhibition activity.