Phage Therapy to Treat Cystic Fibrosis Complex Lung Infections: Perspectives and Challenges

Overview

Journal Front Microbiol

Specialty Microbiology

Date 2024 Nov 4

PMID 39493847

Authors

Jack S Canning

Daniel R Laucirica

Kak-Ming Ling

Mark P Nicol

Stephen M Stick

Anthony Kicic

Affiliations

Soon will be listed here.

Abstract

complex is a cause of serious lung infections in people with cystic fibrosis, exhibiting extremely high levels of antimicrobial resistance. These infections are difficult to treat and are associated with high morbidity and mortality. With a notable lack of new antibiotic classes currently in development, exploring alternative antimicrobial strategies for complex is crucial. One potential alternative seeing renewed interest is the use of bacteriophage (phage) therapy. This review summarises what is currently known about complex in cystic fibrosis, as well as challenges and insights for using phages to treat complex lung infections.

Citing Articles

Bacteriophages: A Challenge for Antimicrobial Therapy.

Segundo-Arizmendi N, Arellano-Maciel D, Rivera-Ramirez A, Pina-Gonzalez A, Lopez-Leal G, Hernandez-Baltazar E Microorganisms. 2025; 13(1).

PMID: 39858868 PMC: 11767365. DOI: 10.3390/microorganisms13010100.

References

Malik D, Sokolov I, Vinner G, Mancuso F, Cinquerrui S, Vladisavljevic G . Formulation, stabilisation and encapsulation of bacteriophage for phage therapy. Adv Colloid Interface Sci. 2017; 249:100-133. DOI: 10.1016/j.cis.2017.05.014. View

Blanchard A, Waters V . Microbiology of Cystic Fibrosis Airway Disease. Semin Respir Crit Care Med. 2019; 40(6):727-736. PMC: 7117079. DOI: 10.1055/s-0039-1698464. View

Howard-Varona C, Hargreaves K, Abedon S, Sullivan M . Lysogeny in nature: mechanisms, impact and ecology of temperate phages. ISME J. 2017; 11(7):1511-1520. PMC: 5520141. DOI: 10.1038/ismej.2017.16. View

Soyza A, Meachery G, Hester K, Nicholson A, Parry G, Tocewicz K . Lung transplantation for patients with cystic fibrosis and Burkholderia cepacia complex infection: a single-center experience. J Heart Lung Transplant. 2010; 29(12):1395-404. DOI: 10.1016/j.healun.2010.06.007. View

Bosso J, Liptak C, Seilheimer D, Harrison G . Toxicity of colistin in cystic fibrosis patients. DICP. 1991; 25(11):1168-70. DOI: 10.1177/106002809102501101. View

Summer E, Gonzalez C, Bomer M, Carlile T, Embry A, Kucherka A . Divergence and mosaicism among virulent soil phages of the Burkholderia cepacia complex. J Bacteriol. 2005; 188(1):255-68. PMC: 1317576. DOI: 10.1128/JB.188.1.255-268.2006. View

Bonyadi P, Saleh N, Dehghani M, Yamini M, Amini K . Prevalence of antibiotic resistance of Pseudomonas aeruginosa in cystic fibrosis infection: A systematic review and meta-analysis. Microb Pathog. 2022; 165:105461. DOI: 10.1016/j.micpath.2022.105461. View

Saluzzo F, Riberi L, Messore B, Lore N, Esposito I, Bignamini E . CFTR Modulator Therapies: Potential Impact on Airway Infections in Cystic Fibrosis. Cells. 2022; 11(7). PMC: 8998122. DOI: 10.3390/cells11071243. View

Bodier-Montagutelli E, Morello E, LHostis G, Guillon A, Dalloneau E, Respaud R . Inhaled phage therapy: a promising and challenging approach to treat bacterial respiratory infections. Expert Opin Drug Deliv. 2016; 14(8):959-972. DOI: 10.1080/17425247.2017.1252329. View

10.

Mayer-Hamblett N, Ramsey B, Kulasekara H, Wolter D, Houston L, Pope C . Pseudomonas aeruginosa phenotypes associated with eradication failure in children with cystic fibrosis. Clin Infect Dis. 2014; 59(5):624-31. PMC: 4148602. DOI: 10.1093/cid/ciu385. View

11.

Zablocki O, Adriaenssens E, Cowan D . Diversity and Ecology of Viruses in Hyperarid Desert Soils. Appl Environ Microbiol. 2015; 82(3):770-7. PMC: 4725269. DOI: 10.1128/AEM.02651-15. View

12.

Keen E, Bliskovsky V, Malagon F, Baker J, Prince J, Klaus J . Novel "Superspreader" Bacteriophages Promote Horizontal Gene Transfer by Transformation. mBio. 2017; 8(1). PMC: 5241400. DOI: 10.1128/mBio.02115-16. View

13.

Courtney J, Dunbar K, McDowell A, Moore J, Warke T, Stevenson M . Clinical outcome of Burkholderia cepacia complex infection in cystic fibrosis adults. J Cyst Fibros. 2004; 3(2):93-8. DOI: 10.1016/j.jcf.2004.01.005. View

14.

Regan K, Bhatt J . Eradication therapy for Burkholderia cepacia complex in people with cystic fibrosis. Cochrane Database Syst Rev. 2019; 4:CD009876. PMC: 6471232. DOI: 10.1002/14651858.CD009876.pub4. View

15.

Nzula S, Vandamme P, Govan J . Sensitivity of the Burkholderia cepacia complex and Pseudomonas aeruginosa to transducing bacteriophages. FEMS Immunol Med Microbiol. 2000; 28(4):307-12. DOI: 10.1111/j.1574-695X.2000.tb01491.x. View

16.

Lynch K, Stothard P, Dennis J . Comparative analysis of two phenotypically-similar but genomically-distinct Burkholderia cenocepacia-specific bacteriophages. BMC Genomics. 2012; 13:223. PMC: 3483164. DOI: 10.1186/1471-2164-13-223. View

17.

Jones A, Dodd M, Webb A . Burkholderia cepacia: current clinical issues, environmental controversies and ethical dilemmas. Eur Respir J. 2001; 17(2):295-301. DOI: 10.1183/09031936.01.17202950. View

18.

Ngiam L, Weynberg K, Guo J . Evolutionary and co-evolutionary phage training approaches enhance bacterial suppression and delay the emergence of phage resistance. ISME Commun. 2024; 4(1):ycae082. PMC: 11234896. DOI: 10.1093/ismeco/ycae082. View

19.

COWDERY J, Chace J, Yi A, Krieg A . Bacterial DNA induces NK cells to produce IFN-gamma in vivo and increases the toxicity of lipopolysaccharides. J Immunol. 1996; 156(12):4570-5. View

20.

Lynch K, Abdu A, Schobert M, Dennis J . Genomic characterization of JG068, a novel virulent podovirus active against Burkholderia cenocepacia. BMC Genomics. 2013; 14:574. PMC: 3765740. DOI: 10.1186/1471-2164-14-574. View