title: Evolution of metabolic divergence in Pseudomonas aeruginosa during long-term infection facilitates a proto-cooperative interspecies interaction.
abstract: The effect of polymicrobial interactions on pathogen physiology and how it can act either to limit pathogen colonization or to potentiate pathogen expansion and virulence are not well understood. Pseudomonas aeruginosa and Staphylococcus aureus are opportunistic pathogens commonly found together in polymicrobial human infections. However, we have previously shown that the interactions between these two bacterial species are strain dependent. Whereas P. aeruginosa PAO1, a commonly used laboratory strain, effectively suppressed S. aureus growth, we observed a commensal-like interaction between the human host-adapted strain, DK2-P2M24-2003, and S. aureus. In this study, characterization by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) imaging mass spectrometry (IMS) and mass spectral (MS) molecular networking revealed a significant metabolic divergence between P. aeruginosa PAO1 and DK2-P2M24-2003, which comprised several virulence factors and signaling 4-hydroxy-2-alkylquinoline (HAQ) molecules. Strikingly, a further modulation of the HAQ profile was observed in DK2-P2M24-2003 during interaction with S. aureus, resulting in an area with thickened colony morphology at the P. aeruginosa-S. aureus interface. In addition, we found an HAQ-mediated protection of S. aureus by DK2-P2M24-2003 from the killing effect of tobramycin. Our findings suggest a model where the metabolic divergence manifested in human host-adapted P. aeruginosa is further modulated during interaction with S. aureus and facilitate a proto-cooperative P. aeruginosa-S. aureus relationship.
authors.affiliation: Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Frydenlund Michelsen
authors.affiliation: Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.
authors.forename: Seyed Mohammad
authors.initials: SM
authors.lastname: Hossein Khademi
authors.affiliation: Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark.|The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Hørsholm, Denmark.
authors.forename: Helle
authors.initials: H
authors.lastname: Krogh Johansen
authors.affiliation: Department of Veterinary Disease Biology, Food Safety and Zoonoses, University of Copenhagen, Frederiksberg C, Denmark.
authors.forename: Hanne
authors.initials: H
authors.lastname: Ingmer
authors.affiliation: Department of Pharmacology, University of California at San Diego, La Jolla, CA, USA.|Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, CA, USA.|Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, La Jolla, CA, USA.
authors.forename: Pieter C
authors.initials: PC
authors.lastname: Dorrestein
authors.affiliation: Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Jelsbak
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D005075:Biological Evolution; D018920:Coculture Techniques; D060085:Coinfection; D054884:Host-Pathogen Interactions; D006801:Humans; D056265:Microbial Interactions; D008954:Models, Biological; D016254:Mutagenesis, Insertional; D010641:Phenotype; D011552:Pseudomonas Infections / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D011804:Quinolines / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013203:Staphylococcal Infections / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D014031:Tobramycin / Q000494:pharmacology; D037521:Virulence Factors
chemical_list: D000900:Anti-Bacterial Agents; D011804:Quinolines; D037521:Virulence Factors; C037219:quinoline; D014031:Tobramycin