title: Staphylococcus aureus alters growth activity, autolysis, and antibiotic tolerance in a human host-adapted Pseudomonas aeruginosa lineage.
abstract: Interactions among members of polymicrobial infections or between pathogens and the commensal flora may determine disease outcomes. Pseudomonas aeruginosa and Staphylococcus aureus are important opportunistic human pathogens and are both part of the polymicrobial infection communities in human hosts. In this study, we analyzed the in vitro interaction between S. aureus and a collection of P. aeruginosa isolates representing different evolutionary steps of a dominant lineage, DK2, that have evolved through decades of growth in chronically infected patients. While the early adapted P. aeruginosa DK2 strains outcompeted S. aureus during coculture on agar plates, we found that later P. aeruginosa DK2 strains showed a commensal-like interaction, where S. aureus was not inhibited by P. aeruginosa and the growth activity of P. aeruginosa was enhanced in the presence of S. aureus. This effect is mediated by one or more extracellular S. aureus proteins greater than 10 kDa, which also suppressed P. aeruginosa autolysis and prevented killing by clinically relevant antibiotics through promoting small-colony variant (SCV) formation. The commensal interaction was abolished with S. aureus strains mutated in the agr quorum sensing system or in the SarA transcriptional virulence regulator, as well as with strains lacking the proteolytic subunit, ClpP, of the Clp protease. Our results show that during evolution of a dominant cystic fibrosis lineage of P. aeruginosa, a commensal interaction potential with S. aureus has developed.
authors.affiliation: Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.
authors.forename: Charlotte Frydenlund
authors.initials: CF
authors.lastname: Michelsen
authors.affiliation: Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.
authors.forename: Anne-Mette Juel
authors.initials: AM
authors.lastname: Christensen
authors.affiliation: Department of Veterinary Disease Biology, Food Safety and Zoonoses, University of Copenhagen, Frederiksberg, Denmark.
authors.forename: Martin Saxtorph
authors.initials: MS
authors.lastname: Bojer
authors.affiliation: Institute for International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Høiby
authors.affiliation: Department of Veterinary Disease Biology, Food Safety and Zoonoses, University of Copenhagen, Frederiksberg, Denmark.
authors.forename: Hanne
authors.initials: H
authors.lastname: Ingmer
authors.affiliation: Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark lj@bio.dtu.dk.
authors.forename: Lars
authors.initials: L
authors.lastname: Jelsbak
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001431:Bacteriological Techniques; D002939:Ciprofloxacin / Q000494:pharmacology; D018920:Coculture Techniques; D024881:Drug Resistance, Bacterial / Q000502:physiology*; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D005839:Gentamicins / Q000494:pharmacology; D058507:Host Specificity; D006801:Humans; D011550:Pseudomonas aeruginosa / Q000145:classification / Q000187:drug effects* / Q000254:growth & development*; D053038:Quorum Sensing; D013211:Staphylococcus aureus / Q000502:physiology*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D005839:Gentamicins; D002939:Ciprofloxacin