Pyochelin biotransformation by Staphylococcus aureus shapes bacterial competition with Pseudomonas aeruginosa in polymicrobial infections
Christian Jenul,
Klara C. Keim,
Justin N. Jens,
Michael J. Zeiler,
Katrin Schilcher,
Michael J. Schurr,
Christian Melander,
Vanessa V. Phelan,
Alexander R. Horswill
Affiliations
Christian Jenul
Department of Immunology and Microbiology, School of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Genetics and Genome Biology, University of Leicester, Leicester LE1 7RH, UK
Klara C. Keim
Department of Immunology and Microbiology, School of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA
Justin N. Jens
Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA
Michael J. Zeiler
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA
Katrin Schilcher
Department of Immunology and Microbiology, School of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Genetics and Genome Biology, University of Leicester, Leicester LE1 7RH, UK
Michael J. Schurr
Department of Immunology and Microbiology, School of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA
Christian Melander
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA
Vanessa V. Phelan
Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA; Corresponding author
Alexander R. Horswill
Department of Immunology and Microbiology, School of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Veterans Affairs, Eastern Colorado Health Care System, Aurora, CO 80045, USA; Corresponding author
Summary: 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.
