TY - JOUR

T1 - Staphylococcus aureus alters growth activity, autolysis and antibiotic tolerance in a human host-adapted Pseudomonas aeruginosa lineage

AU - Michelsen, Charlotte Frydenlund

AU - Christensen, Anne-Mette Juel

AU - Bojer, Martin Saxtorph

AU - Høiby, Niels

AU - Ingmer, Hanne

AU - Jelsbak, Lars

N1 - Copyright © 2014, American Society for Microbiology. All Rights Reserved.

PY - 2014

Y1 - 2014

N2 - 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 co-culture 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 the transcriptional virulence regulator, SarA 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.

AB - 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 co-culture 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 the transcriptional virulence regulator, SarA 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.

U2 - 10.1128/JB.02006-14

DO - 10.1128/JB.02006-14

M3 - Journal article

C2 - 25182495

VL - 196

SP - 3903

EP - 3911

JO - Journal of Bacteriology

JF - Journal of Bacteriology

SN - 0021-9193

IS - 22

ER -