Pyochelin biotransformation by Staphylococcus aureus shapes bacterial competition with Pseudomonas aeruginosa in polymicrobial infections

• Published in: Cell reports (Cambridge) 2023-06, Vol.42 (6), p.112540-112540, Article 112540
• Main Authors: Jenul, Christian, Keim, Klara C., Jens, Justin N., Zeiler, Michael J., Schilcher, Katrin, Schurr, Michael J., Melander, Christian, Phelan, Vanessa V., Horswill, Alexander R.
• Format: Article
• Language: English
• Subjects: Animals; biotransformation; Coinfection - microbiology; CP: Microbiology; Humans; Mice; MRSA; Pseudomonas aeruginosa; Pseudomonas aeruginosa - metabolism; pyochelin; Staphylococcal Infections - microbiology; Staphylococcus aureus; Staphylococcus aureus - physiology
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2023.112540

Pseudomonas aeruginosa and Staphylococcus aureus are among the most frequently isolated bacterial species from polymicrobial infections of patients with cystic fibrosis and chronic wounds. We apply 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 reactive oxygen species (ROS) production in S. aureus. In a murine wound co-infection model, an S. aureus mutant unable to methylate pyochelin shows significantly lower fitness compared with its parental strain. Thus, Spm-mediated pyochelin methylation is a mechanism to increase S. aureus survival during in vivo competition with P. aeruginosa. [Display omitted] •Staphylococcus aureus methylates pyochelin produced by Pseudomonas aeruginosa•Pyochelin is methylated by the staphylococcal pyochelin methyltransferase (Spm)•Pyochelin loses its biological activity upon Spm-mediated methylation•Pyochelin methylation increases S. aureus fitness in co-infections with P. aeruginosa Jenul et al. report that Staphylococcus aureus inactivates the Pseudomonas aeruginosa-derived siderophore pyochelin by methylation. Pyochelin methylation is dependent on the enzyme staphylococcal pyochelin methyltransferase (Spm) and increases S. aureus fitness in co-infections with P. aeruginosa.