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Published December 2023 | Published
Journal Article Open

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

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.

Copyright and License

© 2023 Cobián Güemes et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

Acknowledgement

We thank the UCSD Clinical Microbiology Laboratory for their participation in this work. We also thank the CDC for their generous sharing of the PSA isolates. We thank Dr. Elizabeth Villa and the EPI consortium for fruitful discussions.

This work was supported by the Howard Hughes Medical Institute Emerging Pathogens Initiative grant (#30207345).

D.T.P. and R.T.S. conceived and designed the project. A.G.C.G., P.G., A.N.B., A.G., J.L., J.O., M.C., P.K., and M.P. performed the experiments. A.G.C.G., P.G., A.N.B., A.G., D.T.P., and R.T.S. analyzed the data. A.G.C.G., P.G., J.P., D.T.P., and R.T.S. wrote and edited the manuscript. S.K. and R.K. provided materials for the study. All authors have reviewed the manuscript.

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Additional details

Created:
December 21, 2023
Modified:
December 21, 2023