Mycobacteria methylate antibacterial compounds
Pseudomonas aeruginosa, a ubiquitous environmental bacterium, is a major cause of nosocomial infections and one of the most prevalent species in infections of the cystic fibrosis lung. It produces an arsenal of virulence factors, among them a range of secondary metabolites which affect host cells and act as antimicrobials. The P. aeruginosa product 2‐heptyl‐1‐hydroxyquinolin‐4(1H)‐one (2‐heptyl‐4‐hydroxyquinoline N‐oxide, HQNO), for example, is a potent inhibitor of respiratory electron transfer.
Mycobacteroides abscessus lives in soil and water, but is increasingly recognized as an opportunistic pathogen in immunocompromised and cystic fibrosis patients, causing accelerated lung damage. Interestingly, M. abscessus is capable of modifying and thus detoxifying the P. aeruginosa toxin HQNO by O-methylation (Thierbach et al. 2017, ACS Chem. Biol. 2(9):2305-2312). In this study, published in The FEBS Journal, the enzyme responsible for HQNO methylation was identified. Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), was found to contain an isofunctional enzyme. The methyltransferases, besides catalyzing the modification of HQNO, also mediate O-methylation of a range of related bio-active compounds and moreover N-methylate the scaffold of an antimycobacterial drug. The newly identified „heterocyclic toxin methyltransferases“ likely contribute to resistance of mycobacteria toward antimicrobial natural compounds as well as drugs.
Institutions involved and funding:
Besides the University or Münster, the Vrije Universiteit Brussels, Belgium, was involved in this study, which received financial support from the German Research Foundation (DFG; FE 383/25-1).
Original publication:
Sartor P, Bock J, Hennecke U, Thierbach S, Fetzner S (2020). Modification of the Pseudomonas aeruginosa toxin 2-heptyl-1-hydroxyquinolin-4(1H)-one and other secondary metabolites by methyltransferases from mycobacteria. First published: 16 October 2020. The FEBS Journal.