Designing a new antimycobacterial peptide to tackle Mycobacterium avium

The incidence of nontuberculous mycobacteria (NTM) infections has been increasing over the last decades and the most prominent NTM infection is caused by the Mycobacterium avium complex (MAC). M. avium is considered an opportunistic pathogen, causing disease in individuals with a history of chronic lung disease or immunosuppression. Treatment of this infection requires a multi-drug regimen, lasting until the patient is culture-negative for one year. Highly toxic to the patient, it is imperative to find new antimicrobial agents.

Antimicrobial peptides (AMP) have taken the role of being the most promising substitute for antibiotics over the last few decades. Found in every living organism, they not only display direct antimicrobial efficacy against viruses, fungi and bacteria but also display anti-inflammatory, anti-cancer and wound healing properties.

Therefore, this work is aimed at testing existing peptides, with reported good activities towards Gram-positive and Gram-negative bacteria, against M. avium. Moreover, using previous knowledge on peptides with good activity against M. avium, we intended to understand what are the key structural and physicochemical properties determining the antimycobacterial effect of a peptide. Taking advantage of in silico predictors of AMP’s antimicrobial activity and toxicity, several peptides were designed and one was chosen for synthesis and for testing against M. avium in vitro.