title: Environmental Pseudomonads Inhibit Cystic Fibrosis Patient-Derived Pseudomonas aeruginosa.
abstract: Pseudomonas aeruginosa is an opportunistic pathogen which is evolving resistance to many currently used antibiotics. While much research has been devoted to the roles of pathogenic P. aeruginosa in cystic fibrosis (CF) patients, less is known of its ecological properties. P. aeruginosa dominates the lungs during chronic infection in CF patients, yet its abundance in some environments is less than that of other diverse groups of pseudomonads. Here, we sought to determine if clinical isolates of P. aeruginosa are vulnerable to environmental pseudomonads that dominate soil and water habitats in one-to-one competitions which may provide a source of inhibitory factors. We isolated a total of 330 pseudomonads from diverse habitats of soil and freshwater ecosystems and competed these strains against one another to determine their capacity for antagonistic activity. Over 900 individual inhibitory events were observed. Extending the analysis to P. aeruginosa isolates revealed that clinical isolates, including ones with increased alginate production, were susceptible to competition by multiple environmental strains. We performed transposon mutagenesis on one isolate and identified an ∼14.8-kb locus involved in antagonistic activity. Only two other environmental isolates were observed to carry the locus, suggesting the presence of additional unique compounds or interactions among other isolates involved in outcompeting P. aeruginosa This collection of strains represents a source of compounds that are active against multiple pathogenic strains. With the evolution of resistance of P. aeruginosa to currently used antibiotics, these environmental strains provide opportunities for novel compound discovery against drug-resistant clinical strains.
  
  
  
  We demonstrate that clinical CF-derived isolates of P. aeruginosa are susceptible to competition in the presence of environmental pseudomonads. We observed that many diverse environmental strains exhibited varied antagonistic profiles against a panel of clinical P. aeruginosa isolates, suggesting the presence of distinct mechanisms of inhibition among these ecological strains. Understanding the properties of these antagonistic events offers the potential for discoveries of antimicrobial compounds or metabolic pathways important to the development of novel treatments for P. aeruginosa infections.
authors.affiliation: Department of Biological Sciences, Bowling Green State University, Bowling Green, Ohio, USA.
authors.forename: Payel
authors.initials: P
authors.lastname: Chatterjee
authors.affiliation: Department of Biological Sciences, Bowling Green State University, Bowling Green, Ohio, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Davis
authors.affiliation: Life Sciences Institute and Departments of Medicinal Chemistry, Chemistry and Microbiology & Immunology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Fengan
authors.initials: F
authors.lastname: Yu
authors.affiliation: Department of Biological Sciences, Bowling Green State University, Bowling Green, Ohio, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: James
authors.affiliation: Department of Biological Sciences, Bowling Green State University, Bowling Green, Ohio, USA.
authors.forename: Julia H
authors.initials: JH
authors.lastname: Wildschutte
authors.affiliation: Department of Biological Sciences, Bowling Green State University, Bowling Green, Ohio, USA.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Wiegmann
authors.affiliation: Life Sciences Institute and Departments of Medicinal Chemistry, Chemistry and Microbiology & Immunology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Sherman
authors.affiliation: Department of Biological Sciences, Bowling Green State University, Bowling Green, Ohio, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: McKay
authors.affiliation: Department of Pediatrics, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: LiPuma
authors.affiliation: Department of Biological Sciences, Bowling Green State University, Bowling Green, Ohio, USA hansw@bgsu.edu.
authors.forename: Hans
authors.initials: H
authors.lastname: Wildschutte
mesh_terms: D000898:Antibiosis; D003550:Cystic Fibrosis / Q000382:microbiology*; D004783:Environmental Microbiology; D006801:Humans; D011549:Pseudomonas / Q000502:physiology*; D011552:Pseudomonas Infections / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000502:physiology*
keywords: Pseudomonas aeruginosa; antagonistic; kynurenine; pseudomonads; siderophore; thioquinolobactin