Jumbo phages are active against extensively drug-resistant eyedrop-associated Pseudomonas aeruginosa infections

Author:

Cobián Güemes Ana Georgina1ORCID,Ghatbale Pooja1,Blanc Alisha N.1,Morgan Chase J.2,Garcia Andrew1,Leonard Jesse1,Huang Lina1,Kovalick Grace1,Proost Marissa1,Chiu Megan1,Kuo Peiting1,Oh Joseph1,Karthikeyan Smruthi34,Knight Rob4567ORCID,Pogliano Joe28,Schooley Robert T.9,Pride David T.189ORCID

Affiliation:

1. Department of Pathology, University of California San Diego, La Jolla, California, USA

2. Department of Biology, University of California San Diego, La Jolla, California, USA

3. Department of Environmental Science and Engineering, Division of Engineering and Applied Science, California Institute of Technology, Pasadena, California, USA

4. Department of Pediatrics, University of California San Diego, La Jolla, California, USA

5. Center for Microbiome Innovation, University of California San Diego, La Jolla, California, USA

6. Department of Bioengineering, University of California San Diego, La Jolla, California, USA

7. Department of Computer Sciences & Engineering, University of California San Diego, La Jolla, California, USA

8. Howard Hughes Medical Institute, University of California San Diego, La Jolla, California, USA

9. Department of Medicine, University of California San Diego, La Jolla, California, USA

Abstract

ABSTRACT Antibiotic-resistant bacteria present an emerging challenge to human health. Their prevalence has been increasing across the globe due in part to the liberal use of antibiotics that has pressured them to develop resistance. Those bacteria that acquire mobile genetic elements are especially concerning because those plasmids may be shared readily with other microbes that can then also become antibiotic resistant. Serious infections have recently been related to the contamination of preservative-free eyedrops with extensively drug-resistant (XDR) isolates of Pseudomonas aeruginosa , already resulting in three deaths. These drug-resistant isolates cannot be managed with most conventional antibiotics. We sought to identify alternatives to conventional antibiotics for the lysis of these XDR isolates and identified multiple bacteriophages (viruses that attack bacteria) that killed them efficiently. We found both jumbo phages (>200 kb in genome size) and non-jumbo phages that were active against these isolates, the former killing more efficiently. Jumbo phages effectively killed the three separate XDR P. aeruginosa isolates both on solid and liquid medium. Given the ongoing nature of the XDR P. aeruginosa eyedrop outbreak, the identification of phages active against them provides physicians with several novel potential alternatives for treatment.

Funder

Howard Hughes Medical Institute

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

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