Development of a Phage Cocktail to Control Proteus Mirabilis Catheter-associated Urinary Tract Infections

Overview

Journal Front Microbiol

Specialty Microbiology

Date 2016 Jul 23

PMID 27446059

Citations 57

Authors

Luis D R Melo

Patricia Veiga

Nuno Cerca

Andrew M Kropinski

Carina Almeida

Joana Azeredo

Sanna Sillankorva

Affiliations

Soon will be listed here.

Abstract

Proteus mirabilis is an enterobacterium that causes catheter-associated urinary tract infections (CAUTIs) due to its ability to colonize and form crystalline biofilms on the catheters surface. CAUTIs are very difficult to treat, since biofilm structures are highly tolerant to antibiotics. Phages have been used widely to control a diversity of bacterial species, however, a limited number of phages for P. mirabilis have been isolated and studied. Here we report the isolation of two novel virulent phages, the podovirus vB_PmiP_5460 and the myovirus vB_PmiM_5461, which are able to target, respectively, 16 of the 26 and all the Proteus strains tested in this study. Both phages have been characterized thoroughly and sequencing data revealed no traces of genes associated with lysogeny. To further evaluate the phages' ability to prevent catheter's colonization by Proteus, the phages adherence to silicone surfaces was assessed. Further tests in phage-coated catheters using a dynamic biofilm model simulating CAUTIs, have shown a significant reduction of P. mirabilis biofilm formation up to 168 h of catheterization. These results highlight the potential usefulness of the two isolated phages for the prevention of surface colonization by this bacterium.

Citing Articles

The rise, fall, and resurgence of phage therapy for urinary tract infection.

Zulk J, Patras K, Maresso A EcoSal Plus. 2024; 12(1):eesp00292023.

PMID: 39665540 PMC: 11636367. DOI: 10.1128/ecosalplus.esp-0029-2023.

Plasma activated water pre-treatment substantially enhances phage activity against biofilms.

Shambharkar A, Thompson T, McClenaghan L, Bourke P, Gilmore B, Skvortsov T Biofilm. 2024; 8:100230.

PMID: 39498232 PMC: 11532937. DOI: 10.1016/j.bioflm.2024.100230.

Synergistic effects of bacteriophage cocktail and antibiotics combinations against extensively drug-resistant Acinetobacter baumannii.

Rastegar S, Skurnik M, Tadjrobehkar O, Samareh A, Samare-Najaf M, Lotfian Z BMC Infect Dis. 2024; 24(1):1208.

PMID: 39455951 PMC: 11515142. DOI: 10.1186/s12879-024-10081-0.

Characterization and genomic analysis phage PmP19, a novel Proteus mirabilis phage with a broad host range.

Han S, Li S, Hu G, Lei M, Li C, Xiao L Arch Virol. 2024; 169(11):221.

PMID: 39412589 DOI: 10.1007/s00705-024-06154-9.

The Development of a Biomimetic Model of Bacteria Migration on Indwelling Urinary Catheter Surfaces.

Cortese Y, Fayne J, Colbert D, Devine D, Fogarty A Biomimetics (Basel). 2024; 9(8).

PMID: 39194470 PMC: 11353059. DOI: 10.3390/biomimetics9080491.

References

Morris N, Stickler D, McLean R . The development of bacterial biofilms on indwelling urethral catheters. World J Urol. 2000; 17(6):345-50. DOI: 10.1007/s003450050159. View

Hadas H, Einav M, Fishov I, Zaritsky A . Bacteriophage T4 development depends on the physiology of its host Escherichia coli. Microbiology (Reading). 1997; 143 ( Pt 1):179-185. DOI: 10.1099/00221287-143-1-179. View

Siddiq D, Darouiche R . New strategies to prevent catheter-associated urinary tract infections. Nat Rev Urol. 2012; 9(6):305-14. DOI: 10.1038/nrurol.2012.68. View

Kropinski A, Mazzocco A, Waddell T, Lingohr E, Johnson R . Enumeration of bacteriophages by double agar overlay plaque assay. Methods Mol Biol. 2008; 501:69-76. DOI: 10.1007/978-1-60327-164-6_7. View

Viertel T, Ritter K, Horz H . Viruses versus bacteria-novel approaches to phage therapy as a tool against multidrug-resistant pathogens. J Antimicrob Chemother. 2014; 69(9):2326-36. DOI: 10.1093/jac/dku173. View

Reardon S . Phage therapy gets revitalized. Nature. 2014; 510(7503):15-6. DOI: 10.1038/510015a. View

Zafar N, Mazumder R, Seto D . CoreGenes: a computational tool for identifying and cataloging "core" genes in a set of small genomes. BMC Bioinformatics. 2002; 3:12. PMC: 111185. DOI: 10.1186/1471-2105-3-12. View

Melo L, Sillankorva S, Ackermann H, Kropinski A, Azeredo J, Cerca N . Isolation and characterization of a new Staphylococcus epidermidis broad-spectrum bacteriophage. J Gen Virol. 2013; 95(Pt 2):506-515. DOI: 10.1099/vir.0.060590-0. View

Bailly-Bechet M, Vergassola M, Rocha E . Causes for the intriguing presence of tRNAs in phages. Genome Res. 2007; 17(10):1486-95. PMC: 1987346. DOI: 10.1101/gr.6649807. View

10.

Saint S, Kowalski C, Kaufman S, Hofer T, Kauffman C, Olmsted R . Preventing hospital-acquired urinary tract infection in the United States: a national study. Clin Infect Dis. 2008; 46(2):243-50. DOI: 10.1086/524662. View

11.

Vinogradov E, Perry M . Structural analysis of the core region of lipopolysaccharides from Proteus mirabilis serotypes O6, O48 and O57. Eur J Biochem. 2000; 267(8):2439-46. DOI: 10.1046/j.1432-1327.2000.01262.x. View

12.

Rahman M, Kim S, Kim S, Seol S, Kim J . Characterization of induced Staphylococcus aureus bacteriophage SAP-26 and its anti-biofilm activity with rifampicin. Biofouling. 2011; 27(10):1087-93. DOI: 10.1080/08927014.2011.631169. View

13.

Ackermann H . Basic phage electron microscopy. Methods Mol Biol. 2008; 501:113-26. DOI: 10.1007/978-1-60327-164-6_12. View

14.

Kall L, Sonnhammer E . Reliability of transmembrane predictions in whole-genome data. FEBS Lett. 2002; 532(3):415-8. DOI: 10.1016/s0014-5793(02)03730-4. View

15.

Gu J, Liu X, Li Y, Han W, Lei L, Yang Y . A method for generation phage cocktail with great therapeutic potential. PLoS One. 2012; 7(3):e31698. PMC: 3291564. DOI: 10.1371/journal.pone.0031698. View

16.

Stickler D, Feneley R . The encrustation and blockage of long-term indwelling bladder catheters: a way forward in prevention and control. Spinal Cord. 2010; 48(11):784-90. DOI: 10.1038/sc.2010.32. View

17.

Azeredo J, Sutherland I . The use of phages for the removal of infectious biofilms. Curr Pharm Biotechnol. 2008; 9(4):261-6. DOI: 10.2174/138920108785161604. View

18.

Wilkins M, Gasteiger E, Bairoch A, Sanchez J, Williams K, Appel R . Protein identification and analysis tools in the ExPASy server. Methods Mol Biol. 1999; 112:531-52. DOI: 10.1385/1-59259-584-7:531. View

19.

Rocha E, Danchin A . Base composition bias might result from competition for metabolic resources. Trends Genet. 2002; 18(6):291-4. DOI: 10.1016/S0168-9525(02)02690-2. View

20.

Lavigne R, Sun W, Volckaert G . PHIRE, a deterministic approach to reveal regulatory elements in bacteriophage genomes. Bioinformatics. 2004; 20(5):629-35. DOI: 10.1093/bioinformatics/btg456. View