Journal article
Exogenous Alginate Protects Staphylococcus aureus from Killing by Pseudomonas aeruginosa
Journal of bacteriology, Vol.202(8), e00559-19
03/26/2020
DOI: 10.1128/JB.00559-19
PMCID: PMC7099135
PMID: 31792010
Abstract
Cystic fibrosis (CF) patients chronically infected with both Pseudomonas aeruginosa and Staphylococcus aureus have worse health outcomes than patients who are monoinfected with either P. aeruginosa or S. aureus We showed previously that mucoid strains of P. aeruginosa can coexist with S. aureus in vitro due to the transcriptional downregulation of several toxic exoproducts typically produced by P. aeruginosa, including siderophores, rhamnolipids, and HQNO (2-heptyl-4-hydroxyquinoline N-oxide). Here, we demonstrate that exogenous alginate protects S. aureus from P. aeruginosa in both planktonic and biofilm coculture models under a variety of nutritional conditions. S. aureus protection in the presence of exogenous alginate is due to the transcriptional downregulation of pvdA, a gene required for the production of the iron-scavenging siderophore pyoverdine as well as the downregulation of the PQS (Pseudomonas quinolone signal) (2-heptyl-3,4-dihydroxyquinoline) quorum sensing system. The impact of exogenous alginate is independent of endogenous alginate production. We further demonstrate that coculture of mucoid P. aeruginosa with nonmucoid P. aeruginosa strains can mitigate the killing of S. aureus by the nonmucoid strain of P. aeruginosa, indicating that the mechanism that we describe here may function in vivo in the context of mixed infections. Finally, we investigated a panel of mucoid clinical isolates that retain the ability to kill S. aureus at late time points and show that each strain has a unique expression profile, indicating that mucoid isolates can overcome the S. aureus-protective effects of mucoidy in a strain-specific manner.IMPORTANCE CF patients are chronically infected by polymicrobial communities. The two dominant bacterial pathogens that infect the lungs of CF patients are P. aeruginosa and S. aureus, with ∼30% of patients coinfected by both species. Such coinfected individuals have worse outcomes than monoinfected patients, and both species persist within the same physical space. A variety of host and environmental factors have been demonstrated to promote P. aeruginosa-S. aureus coexistence, despite evidence that P. aeruginosa kills S. aureus when these organisms are cocultured in vitro Thus, a better understanding of P. aeruginosa-S. aureus interactions, particularly mechanisms by which these microorganisms are able to coexist in proximal physical space, will lead to better-informed treatments for chronic polymicrobial infections.
Details
- Title: Subtitle
- Exogenous Alginate Protects Staphylococcus aureus from Killing by Pseudomonas aeruginosa
- Creators
- Courtney E Price - Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hannover, New Hampshire, USADustin G Brown - Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, Colorado, USADominique H Limoli - Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa, USAVanessa V Phelan - Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, Colorado, USAGeorge A O'Toole - Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hannover, New Hampshire, USA georgeo@dartmouth.edu
- Resource Type
- Journal article
- Publication Details
- Journal of bacteriology, Vol.202(8), e00559-19
- Publisher
- United States
- DOI
- 10.1128/JB.00559-19
- PMID
- 31792010
- PMCID
- PMC7099135
- ISSN
- 0021-9193
- eISSN
- 1098-5530
- Grant note
- R37 AI083256 / NIAID NIH HHS T32 AI007363 / NIAID NIH HHS R35 GM128690 / NIGMS NIH HHS P30 DK117469 / NIDDK NIH HHS P30 DK054759 / NIDDK NIH HHS
- Language
- English
- Date published
- 03/26/2020
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984067699402771
Metrics
17 Record Views