Phage therapy administered noninvasively could be effective in thin tubes subject to episodic flow despite washout: a simulation study
Bacteriophages (phages) have been proposed as candidates for the treatment of bacterial infections in light of emerging antibiotic-resistant microorganisms. Bacterial growth within thin tubes is a particular concern, such as in urinary tract infections and colonization of catheters. However, it is n...
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Published in | Physical biology Vol. 16; no. 5; p. 54001 |
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Main Authors | , |
Format | Journal Article |
Language | English |
Published |
England
IOP Publishing
22.07.2019
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Online Access | Get full text |
ISSN | 1478-3967 1478-3975 1478-3975 |
DOI | 10.1088/1478-3975/ab2ea0 |
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Abstract | Bacteriophages (phages) have been proposed as candidates for the treatment of bacterial infections in light of emerging antibiotic-resistant microorganisms. Bacterial growth within thin tubes is a particular concern, such as in urinary tract infections and colonization of catheters. However, it is not clear whether phage administration to the urinary tract or in catheters could be effective in the context of flow to the outside (i.e. voiding or saline flush). Here, we adapt a previous model of phage infection to a thin tube geometry mimicking the spatial organization of the urinary tract, including bacterial motility and episodic flow during which phages are washed out of the system. We show that density-dependent dynamics permit propagation of the phage infection and that washout has little effect on the timing of bacterial clearance. In addition, instillation of phage at the bottom ~0.1 mm of the tract is effective in our computational model, suggesting that therapeutic phage introduced non-invasively could be efficacious in such situations. |
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AbstractList | Bacteriophages (phages) have been proposed as candidates for the treatment of bacterial infections in light of emerging antibiotic-resistant microorganisms. Bacterial growth within thin tubes is a particular concern, such as in urinary tract infections and colonization of catheters. However, it is not clear whether phage administration to the urinary tract or in catheters could be effective in the context of flow to the outside (i.e. voiding or saline flush). Here, we adapt a previous model of phage infection to a thin tube geometry mimicking the spatial organization of the urinary tract, including bacterial motility and episodic flow during which phages are washed out of the system. We show that density-dependent dynamics permit propagation of the phage infection and that washout has little effect on the timing of bacterial clearance. In addition, instillation of phage at the bottom ~0.1 mm of the tract is effective in our computational model, suggesting that therapeutic phage introduced non-invasively could be efficacious in such situations. Bacteriophages (phages) have been proposed as candidates for the treatment of bacterial infections in light of emerging antibiotic-resistant microorganisms. Bacterial growth within thin tubes is a particular concern, such as in urinary tract infections and colonization of catheters. However, it is not clear whether phage administration to the urinary tract or in catheters could be effective in the context of flow to the outside (i.e. voiding or saline flush). Here, we adapt a previous model of phage infection to a thin tube geometry mimicking the spatial organization of the urinary tract, including bacterial motility and episodic flow during which phages are washed out of the system. We show that density-dependent dynamics permit propagation of the phage infection and that washout has little effect on the timing of bacterial clearance. In addition, instillation of phage at the bottom ~0.1 mm of the tract is effective in our computational model, suggesting that therapeutic phage introduced non-invasively could be efficacious in such situations.Bacteriophages (phages) have been proposed as candidates for the treatment of bacterial infections in light of emerging antibiotic-resistant microorganisms. Bacterial growth within thin tubes is a particular concern, such as in urinary tract infections and colonization of catheters. However, it is not clear whether phage administration to the urinary tract or in catheters could be effective in the context of flow to the outside (i.e. voiding or saline flush). Here, we adapt a previous model of phage infection to a thin tube geometry mimicking the spatial organization of the urinary tract, including bacterial motility and episodic flow during which phages are washed out of the system. We show that density-dependent dynamics permit propagation of the phage infection and that washout has little effect on the timing of bacterial clearance. In addition, instillation of phage at the bottom ~0.1 mm of the tract is effective in our computational model, suggesting that therapeutic phage introduced non-invasively could be efficacious in such situations. |
Author | Blanco, Celia Chen, Irene A |
AuthorAffiliation | 1 Department of Chemistry and Biochemistry 9510, University of California, Santa Barbara, CA 93106, United States of America 4 Author to whom any correspondence should be addressed 2 Program in Biomolecular Sciences and Engineering, University of California, Santa Barbara, CA 93106, United States of America 3 Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, CA 90095, United States of America |
AuthorAffiliation_xml | – name: 3 Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, CA 90095, United States of America – name: 1 Department of Chemistry and Biochemistry 9510, University of California, Santa Barbara, CA 93106, United States of America – name: 2 Program in Biomolecular Sciences and Engineering, University of California, Santa Barbara, CA 93106, United States of America – name: 4 Author to whom any correspondence should be addressed |
Author_xml | – sequence: 1 givenname: Celia orcidid: 0000-0003-1536-1493 surname: Blanco fullname: Blanco, Celia organization: University of California Department of Chemistry and Biochemistry 9510, Santa Barbara, CA 93106, United States of America – sequence: 2 givenname: Irene A orcidid: 0000-0001-6040-7927 surname: Chen fullname: Chen, Irene A email: chen@chem.ucsb.edu organization: Author to whom any correspondence should be addressed |
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SubjectTerms | Bacteria - growth & development Bacteria - virology Bacterial Infections - therapy Bacteriophages - physiology computational model Models, Biological phage therapy Phage Therapy - methods urinary tract infection |
Title | Phage therapy administered noninvasively could be effective in thin tubes subject to episodic flow despite washout: a simulation study |
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