Pyochelin biotransformation shapes bacterial competition Christian Jenul 1 , Klara Keim 1 , Justin Jens 2 , Michael J. Zeiler 3 , Katrin Schilcher 1 , Michael Schurr 1 , Christian Melander 3 , Vanessa V. Phelan 2 , Alexander R. Horswill 1, 4 1 Department of Immunology and Microbiology, University of Colorado,USA, 2 Department of Pharmaceutical Sciences, University of Colorado, USA, 3 Department of Chemistry and Biochemistry, University of Notre Dame, USA, 4 Department of Veterans Affairs, Eastern Colorado Health Care System, USA It has become evident that numerous infections are polymicrobial and Pseudomonas aeruginosa and Staphylococcus aureus are among the most frequently co-isolated bacterial species from cystic fibrosis lung infections and chronic wounds (1-4). We applied mass spectrometry guided interaction studies and molecular networking 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, inactivation of the siderophore pyochelin via the yet uncharacterized methyltransferase Spm ( s taphylococcal p yochelin m ethyltransferase), to increase its survival during in vivo competition with P. aeruginosa . 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 significant lower fitness compared to its parental strain. References 1. C. F. F. P. Registry, 2019 Annual Data Report. ©2020 Cystic Fibrosis Foundation , (2019).K. Gjodsbol et al. , Multiple bacterial species reside in chronic wounds: a longitudinal study. Int Wound J 3 , 225-231 (2006). 2. A. Korber et al. , Bacterial colonization of chronic leg ulcers: current results compared with data 5 years ago in a specialized dermatology department. J Eur Acad Dermatol Venereol 24 , 1017-1025 (2010). 3. L. J. Bessa, P. Fazii, M. Di Giulio, L. Cellini, Bacterial isolates from infected wounds and their antibiotic susceptibility pattern: some remarks about wound infection. Int Wound J 12 , 47-52 (2015).
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