Broad-range capsule-dependent lytic Sugarlandvirus against Klebsiella sp.
ABSTRACT The emergence of antibiotic-resistant bacteria has become a serious global health threat requiring the development of novel treatments. Klebsiella pneumoniae is an encapsulated bacterium considered a major concern due to its high resistance, prevalence, and mortality rates. Phage therapy ha...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2023-12-01
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| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.04298-22 |
| _version_ | 1797393633818705920 |
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| author | Robby Concha-Eloko Pilar Barberán-Martínez Rafael Sanjuán Pilar Domingo-Calap |
| author_facet | Robby Concha-Eloko Pilar Barberán-Martínez Rafael Sanjuán Pilar Domingo-Calap |
| author_sort | Robby Concha-Eloko |
| collection | DOAJ |
| description | ABSTRACT The emergence of antibiotic-resistant bacteria has become a serious global health threat requiring the development of novel treatments. Klebsiella pneumoniae is an encapsulated bacterium considered a major concern due to its high resistance, prevalence, and mortality rates. Phage therapy has been proposed as a very promising alternative to combat infections by Klebsiella sp. infections. However, most of the Klebsiella phages described so far present a high specificity, infecting one or a few capsular types due to the presence of depolymerases in their genomes, which limits their therapeutic potential. Here, we present three new Klebsiella phages isolated from the environment, vB_Kpn_K7PH164C4, vB_Kpn_K30λ2.2, and vB_Kpl_K32PH164C1, belonging to the family Demerecviridae and the genus Sugarlandvirus. The most important feature of these new Klebsiella phages is their broad host range, especially vB_Kpn_K7PH164C4 and vB_Kpn_K30λ2.2, which infects strains of more than 20 different capsular types, representing the broadest infection range observed for Klebsiella phages. Genomic analysis revealed the presence of three receptor-binding proteins lacking depolymerase domains. Nevertheless, capsule expression is suggested to be a determining factor in phage infectivity, despite the absence of depolymerase activity against capsular components. Our findings hold potential for the development of promising phage-based therapeutics directed against K. pneumoniae. IMPORTANCE The emergence of multi-drug resistant bacteria is a global health problem. Among them, Klebsiella pneumoniae is considered a high-priority pathogen, making it necessary to develop new therapeutic tools to reduce the bacterial burden in an effective and sustainable manner. Phages, bacterial viruses, are very promising tools. However, phages are highy specific, rendering large-scale therapeutics costly to implement. This is especially certain in Klebsiella, a capsular bacterium in which phages have been shown to be capsular type dependent, infecting one or a few capsular types through specific enzymes called depolymerases. In this study, we have isolated and characterized novel phages with lytic ability against bacteria from a wide variety of capsular types, representing the Klebsiella phages with the widest range of infection described. Remarkably, these broad-range phages showed capsule dependency, despite the absence of depolymerases in their genomes, implying that infectivity could be governed by alternative mechanisms yet to be uncovered. |
| first_indexed | 2024-03-09T00:06:40Z |
| format | Article |
| id | doaj.art-d5d7bef02b254ca2b4688813ff15ef0a |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-03-09T00:06:40Z |
| publishDate | 2023-12-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-d5d7bef02b254ca2b4688813ff15ef0a2023-12-12T13:17:19ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972023-12-0111610.1128/spectrum.04298-22Broad-range capsule-dependent lytic Sugarlandvirus against Klebsiella sp.Robby Concha-Eloko0Pilar Barberán-Martínez1Rafael Sanjuán2Pilar Domingo-Calap3Instituto de Biología Integrativa de Sistemas, Universitat de València-CSIC , Paterna, SpainInstituto de Biología Integrativa de Sistemas, Universitat de València-CSIC , Paterna, SpainInstituto de Biología Integrativa de Sistemas, Universitat de València-CSIC , Paterna, SpainInstituto de Biología Integrativa de Sistemas, Universitat de València-CSIC , Paterna, SpainABSTRACT The emergence of antibiotic-resistant bacteria has become a serious global health threat requiring the development of novel treatments. Klebsiella pneumoniae is an encapsulated bacterium considered a major concern due to its high resistance, prevalence, and mortality rates. Phage therapy has been proposed as a very promising alternative to combat infections by Klebsiella sp. infections. However, most of the Klebsiella phages described so far present a high specificity, infecting one or a few capsular types due to the presence of depolymerases in their genomes, which limits their therapeutic potential. Here, we present three new Klebsiella phages isolated from the environment, vB_Kpn_K7PH164C4, vB_Kpn_K30λ2.2, and vB_Kpl_K32PH164C1, belonging to the family Demerecviridae and the genus Sugarlandvirus. The most important feature of these new Klebsiella phages is their broad host range, especially vB_Kpn_K7PH164C4 and vB_Kpn_K30λ2.2, which infects strains of more than 20 different capsular types, representing the broadest infection range observed for Klebsiella phages. Genomic analysis revealed the presence of three receptor-binding proteins lacking depolymerase domains. Nevertheless, capsule expression is suggested to be a determining factor in phage infectivity, despite the absence of depolymerase activity against capsular components. Our findings hold potential for the development of promising phage-based therapeutics directed against K. pneumoniae. IMPORTANCE The emergence of multi-drug resistant bacteria is a global health problem. Among them, Klebsiella pneumoniae is considered a high-priority pathogen, making it necessary to develop new therapeutic tools to reduce the bacterial burden in an effective and sustainable manner. Phages, bacterial viruses, are very promising tools. However, phages are highy specific, rendering large-scale therapeutics costly to implement. This is especially certain in Klebsiella, a capsular bacterium in which phages have been shown to be capsular type dependent, infecting one or a few capsular types through specific enzymes called depolymerases. In this study, we have isolated and characterized novel phages with lytic ability against bacteria from a wide variety of capsular types, representing the Klebsiella phages with the widest range of infection described. Remarkably, these broad-range phages showed capsule dependency, despite the absence of depolymerases in their genomes, implying that infectivity could be governed by alternative mechanisms yet to be uncovered.https://journals.asm.org/doi/10.1128/spectrum.04298-22Klebsiellabacteriophagescapsulephage therapyinfection rangephage cocktail |
| spellingShingle | Robby Concha-Eloko Pilar Barberán-Martínez Rafael Sanjuán Pilar Domingo-Calap Broad-range capsule-dependent lytic Sugarlandvirus against Klebsiella sp. Microbiology Spectrum Klebsiella bacteriophages capsule phage therapy infection range phage cocktail |
| title | Broad-range capsule-dependent lytic Sugarlandvirus against Klebsiella sp. |
| title_full | Broad-range capsule-dependent lytic Sugarlandvirus against Klebsiella sp. |
| title_fullStr | Broad-range capsule-dependent lytic Sugarlandvirus against Klebsiella sp. |
| title_full_unstemmed | Broad-range capsule-dependent lytic Sugarlandvirus against Klebsiella sp. |
| title_short | Broad-range capsule-dependent lytic Sugarlandvirus against Klebsiella sp. |
| title_sort | broad range capsule dependent lytic sugarlandvirus against klebsiella sp |
| topic | Klebsiella bacteriophages capsule phage therapy infection range phage cocktail |
| url | https://journals.asm.org/doi/10.1128/spectrum.04298-22 |
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