Natural Products Lysobactin and Sorangicin A Show In Vitro Activity against Mycobacterium abscessus Complex

Abstract

ABSTRACT The prevalence of lung disease caused by Mycobacterium abscessus is increasing among patients with cystic fibrosis. M. abscessus is a multidrug resistant opportunistic pathogen that is notoriously difficult to treat due to a lack of efficacious therapeutic regimens. Currently, there are no standard regimens, and treatment guidelines are based empirically on drug susceptibility testing. Thus, novel antibiotics are required. Natural products represent a vast pool of biologically active compounds that have a history of being a good source of antibiotics. Here, we screened a library of 517 natural products purified from fermentations of various bacteria, fungi, and plants against M. abscessus ATCC 19977. Lysobactin and sorangicin A were active against the M. abscessus complex and drug resistant clinical isolates. These natural products merit further consideration to be included in the M. abscessus drug pipeline. IMPORTANCE The many thousands of people living with cystic fibrosis are at a greater risk of developing a chronic lung infection caused by Mycobacterium abscessus. Since M. abscessus is clinically resistant to most anti-TB drugs available, treatment options are limited to macrolides. Despite macrolide-based therapies, cure rates for M. abscessus lung infections are 50%. Using an in-house library of curated natural products, we identified lysobactin and sorangicin A as novel scaffolds for the future development of antimicrobials for patients with M. abscessus infections.

Keywords

• Mycobacterium abscessus
• natural products
• lysobactin
• sorangicin A