Mycobacterium abscessus (Mab) is a rapidly growing mycobacterium that causes chronic pulmonary infections in people with cystic fibrosis (CF). High rates of antimicrobial resistance are seen in Mab, and people experience multiple relapses with low cure rates.
Currently, the therapy of Mab infections involves anti-mycobacterial drugs identified to treat M. tuberculosis infection that is a completely different microorganism for its structure, biochemical patterns, mode of growth and physio-pathogenicity. To date, no drugs completely designed to be active against Mab infections have been introduced in therapy. Research about anti-Mab drugs is still in its infancy due to the poor knowledge about this emerging pathogen.
The project aims to contribute to contrast Mab spread by a two-pronged strategy. In the first strategy researchers will exploit an in-house library of compounds or others selected from the literature testing those against a laboratory strain of the pathogen (Mab ATCC 19977). The second one will take advantage of High Throughput Screening (HTS) procedures already reported in literature, selecting Hit compounds not yet developed by other medicinal chemistry groups, to find interesting anti-Mab compounds among available molecules A cycle of design/chemical modification/biological evaluation will be performed on the most promising compounds to improve their anti-Mab and anti-biofilm activity, and improve the drug-like properties, thus obtaining anti-Mab compounds ready for studies on clinical isolates.
The main objective is to identify some very interesting molecules, endowed with potent anti-Mab activity, low toxicity for the patient, with oral or aerosol administration ready to be tested in animal models of infection.
Results collected in this study could advance knowledge in the field of nontuberculous mycobacteria, opening the way to an effective anti-Mab therapy able also to reduce the time of treatment; and to the future identification of effective therapies for other species such as Mycobacterium avium complex or other threatening pathogens.