Pyochelin Biotransformation by Staphylococcus aureus Shapes Bacterial Competition With Pseudomonas aeruginosa in Polymicrobial Infections

Abstract

Pseudomonas aeruginosa and Staphylococcus aureus are among the most frequently isolated bacterial species from polymicrobial infections of cystic fibrosis patients and chronic wounds. We applied mass spectrometry guided interaction studies to determine how chemical interaction shapes the fitness and community structure during co-infection of these two pathogens. We demonstrate that S. aureus is equipped with an elegant mechanism to inactivate pyochelin via the yet uncharacterized methyltransferase Spm (staphylococcal pyochelin methyltransferase). Methylation of pyochelin abolishes the siderophore activity of pyochelin and significantly lowers pyochelin-mediated intracellular ROS production in S. aureus. In a murine wound co-infection model, a S. aureus mutant unable to methylate pyochelin shows significantly lower fitness as compared to its parental strain. Thus, Spm mediated pyochelin methylation is a novel mechanism to increase S. aureus survival during in vivo competition with P. aeruginosa.

Funding Information: Supported by Swiss National Science Foundation Early PostDoc mobility Fellowship P2ZHP3_168585 (C.J.), by American Heart Association (AHA) postdoctoral fellowship 20POST35220011 (K.S.), NIH public health service grant AI083211, AI153185, AI166805 (A.R.H.) and DE022350 (C.M.), and NIH NIGMS R35 GM128690 (V.V.P.).

Declaration of Interests: Authors declare that they have no competing interests.

Ethics Approval Statement: All animal studies described herein were performed in accordance with best practices outlined by the Office of Laboratory Animal Resources (OLAR) and Institutional Animal Care and Use Committee (IACUC) at the University of Colorado (protocol #00987).

Keywords: Staphylococcus aureus, MRSA, pyochelin, biotransformation, Pseudomonas aeruginosa