Therapeutic Application of Phage Capsule Depolymerases against K1, K5, and K30 Capsulated E. coli in Mice
Capsule depolymerase enzymes offer a promising class of new antibiotics. In vivo studies are encouraging but it is unclear how well this type of phage product will generalize in therapeutics, or whether different depolymerases against the same capsule function similarly. Here, in vivo efficacy was t...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-11-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fmicb.2017.02257/full |
| _version_ | 1819330639773564928 |
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| author | Han Lin Matthew L. Paff Matthew L. Paff Ian J. Molineux Ian J. Molineux James J. Bull James J. Bull James J. Bull |
| author_facet | Han Lin Matthew L. Paff Matthew L. Paff Ian J. Molineux Ian J. Molineux James J. Bull James J. Bull James J. Bull |
| author_sort | Han Lin |
| collection | DOAJ |
| description | Capsule depolymerase enzymes offer a promising class of new antibiotics. In vivo studies are encouraging but it is unclear how well this type of phage product will generalize in therapeutics, or whether different depolymerases against the same capsule function similarly. Here, in vivo efficacy was tested using cloned bacteriophage depolymerases against Escherichia coli strains with three different capsule types: K1, K5, and K30. When treating infections with the cognate capsule type in a mouse thigh model, the previously studied K1E depolymerase rescued poorly, whereas K1F, K1H, K5, and K30 depolymerases rescued well. K30 gp41 was identified as the catalytically active protein. In contrast to the in vivo studies, K1E enzyme actively degraded K1 capsule polysaccharide in vitro and sensitized K1 bacteria to serum killing. The only in vitro correlate of poor K1E performance in vivo was that the purified enzyme did not form the expected trimer. K1E appeared as an 18-mer which might limit its in vivo distribution. Overall, depolymerases were easily identified, cloned from phage genomes, and as purified proteins they proved generally effective. |
| first_indexed | 2024-12-24T14:01:44Z |
| format | Article |
| id | doaj.art-2deb309e886c424da8be64a0bca97e97 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-24T14:01:44Z |
| publishDate | 2017-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-2deb309e886c424da8be64a0bca97e972022-12-21T16:52:27ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2017-11-01810.3389/fmicb.2017.02257292603Therapeutic Application of Phage Capsule Depolymerases against K1, K5, and K30 Capsulated E. coli in MiceHan Lin0Matthew L. Paff1Matthew L. Paff2Ian J. Molineux3Ian J. Molineux4James J. Bull5James J. Bull6James J. Bull7Department of Integrative Biology, The University of Texas at Austin, Austin, TX, United StatesDepartment of Integrative Biology, The University of Texas at Austin, Austin, TX, United StatesInstitute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX, United StatesInstitute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX, United StatesDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX, United StatesDepartment of Integrative Biology, The University of Texas at Austin, Austin, TX, United StatesInstitute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX, United StatesCenter for Computational Biology and Bioinformatics, The University of Texas at Austin, Austin, TX, United StatesCapsule depolymerase enzymes offer a promising class of new antibiotics. In vivo studies are encouraging but it is unclear how well this type of phage product will generalize in therapeutics, or whether different depolymerases against the same capsule function similarly. Here, in vivo efficacy was tested using cloned bacteriophage depolymerases against Escherichia coli strains with three different capsule types: K1, K5, and K30. When treating infections with the cognate capsule type in a mouse thigh model, the previously studied K1E depolymerase rescued poorly, whereas K1F, K1H, K5, and K30 depolymerases rescued well. K30 gp41 was identified as the catalytically active protein. In contrast to the in vivo studies, K1E enzyme actively degraded K1 capsule polysaccharide in vitro and sensitized K1 bacteria to serum killing. The only in vitro correlate of poor K1E performance in vivo was that the purified enzyme did not form the expected trimer. K1E appeared as an 18-mer which might limit its in vivo distribution. Overall, depolymerases were easily identified, cloned from phage genomes, and as purified proteins they proved generally effective.http://journal.frontiersin.org/article/10.3389/fmicb.2017.02257/fullbacterial capsulephagecapsule depolymeraseinfectionantibiotic |
| spellingShingle | Han Lin Matthew L. Paff Matthew L. Paff Ian J. Molineux Ian J. Molineux James J. Bull James J. Bull James J. Bull Therapeutic Application of Phage Capsule Depolymerases against K1, K5, and K30 Capsulated E. coli in Mice Frontiers in Microbiology bacterial capsule phage capsule depolymerase infection antibiotic |
| title | Therapeutic Application of Phage Capsule Depolymerases against K1, K5, and K30 Capsulated E. coli in Mice |
| title_full | Therapeutic Application of Phage Capsule Depolymerases against K1, K5, and K30 Capsulated E. coli in Mice |
| title_fullStr | Therapeutic Application of Phage Capsule Depolymerases against K1, K5, and K30 Capsulated E. coli in Mice |
| title_full_unstemmed | Therapeutic Application of Phage Capsule Depolymerases against K1, K5, and K30 Capsulated E. coli in Mice |
| title_short | Therapeutic Application of Phage Capsule Depolymerases against K1, K5, and K30 Capsulated E. coli in Mice |
| title_sort | therapeutic application of phage capsule depolymerases against k1 k5 and k30 capsulated e coli in mice |
| topic | bacterial capsule phage capsule depolymerase infection antibiotic |
| url | http://journal.frontiersin.org/article/10.3389/fmicb.2017.02257/full |
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