Functional domains of Acinetobacter bacteriophage tail fibers
A rapid increase in antimicrobial resistant bacterial infections around the world is causing a global health crisis. The Gram-negative bacterium Acinetobacter baumannii is categorized as a Priority 1 pathogen for research and development of new antimicrobials by the World Health Organization due to...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-04-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2024.1230997/full |
| _version_ | 1797205910069706752 |
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| author | Danielle L. Peters Francis Gaudreault Wangxue Chen Wangxue Chen |
| author_facet | Danielle L. Peters Francis Gaudreault Wangxue Chen Wangxue Chen |
| author_sort | Danielle L. Peters |
| collection | DOAJ |
| description | A rapid increase in antimicrobial resistant bacterial infections around the world is causing a global health crisis. The Gram-negative bacterium Acinetobacter baumannii is categorized as a Priority 1 pathogen for research and development of new antimicrobials by the World Health Organization due to its numerous intrinsic antibiotic resistance mechanisms and ability to quickly acquire new resistance determinants. Specialized phage enzymes, called depolymerases, degrade the bacterial capsule polysaccharide layer and show therapeutic potential by sensitizing the bacterium to phages, select antibiotics, and serum killing. The functional domains responsible for the capsule degradation activity are often found in the tail fibers of select A. baumannii phages. To further explore the functional domains associated with depolymerase activity, tail-associated proteins of 71 sequenced and fully characterized phages were identified from published literature and analyzed for functional domains using InterProScan. Multisequence alignments and phylogenetic analyses were conducted on the domain groups and assessed in the context of noted halo formation or depolymerase characterization. Proteins derived from phages noted to have halo formation or a functional depolymerase, but no functional domain hits, were modeled with AlphaFold2 Multimer, and compared to other protein models using the DALI server. The domains associated with depolymerase function were pectin lyase-like (SSF51126), tailspike binding (cd20481), (Trans)glycosidases (SSF51445), and potentially SGNH hydrolases. These findings expand our knowledge on phage depolymerases, enabling researchers to better exploit these enzymes for therapeutic use in combating the antimicrobial resistance crisis. |
| first_indexed | 2024-04-24T08:58:37Z |
| format | Article |
| id | doaj.art-6db7587099944488b786cc410333c073 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-24T08:58:37Z |
| publishDate | 2024-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-6db7587099944488b786cc410333c0732024-04-16T05:00:40ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2024-04-011510.3389/fmicb.2024.12309971230997Functional domains of Acinetobacter bacteriophage tail fibersDanielle L. Peters0Francis Gaudreault1Wangxue Chen2Wangxue Chen3Human Health Therapeutics (HHT) Research Center, National Research Council Canada, Ottawa, ON, CanadaHHT Research Center, NRC, Montreal, QC, CanadaHuman Health Therapeutics (HHT) Research Center, National Research Council Canada, Ottawa, ON, CanadaDepartment of Biology, Brock University, St. Catharines, ON, CanadaA rapid increase in antimicrobial resistant bacterial infections around the world is causing a global health crisis. The Gram-negative bacterium Acinetobacter baumannii is categorized as a Priority 1 pathogen for research and development of new antimicrobials by the World Health Organization due to its numerous intrinsic antibiotic resistance mechanisms and ability to quickly acquire new resistance determinants. Specialized phage enzymes, called depolymerases, degrade the bacterial capsule polysaccharide layer and show therapeutic potential by sensitizing the bacterium to phages, select antibiotics, and serum killing. The functional domains responsible for the capsule degradation activity are often found in the tail fibers of select A. baumannii phages. To further explore the functional domains associated with depolymerase activity, tail-associated proteins of 71 sequenced and fully characterized phages were identified from published literature and analyzed for functional domains using InterProScan. Multisequence alignments and phylogenetic analyses were conducted on the domain groups and assessed in the context of noted halo formation or depolymerase characterization. Proteins derived from phages noted to have halo formation or a functional depolymerase, but no functional domain hits, were modeled with AlphaFold2 Multimer, and compared to other protein models using the DALI server. The domains associated with depolymerase function were pectin lyase-like (SSF51126), tailspike binding (cd20481), (Trans)glycosidases (SSF51445), and potentially SGNH hydrolases. These findings expand our knowledge on phage depolymerases, enabling researchers to better exploit these enzymes for therapeutic use in combating the antimicrobial resistance crisis.https://www.frontiersin.org/articles/10.3389/fmicb.2024.1230997/fullAcinetobacterbacteriophageprotein domainsdepolymerasepectin lyasetail spike |
| spellingShingle | Danielle L. Peters Francis Gaudreault Wangxue Chen Wangxue Chen Functional domains of Acinetobacter bacteriophage tail fibers Frontiers in Microbiology Acinetobacter bacteriophage protein domains depolymerase pectin lyase tail spike |
| title | Functional domains of Acinetobacter bacteriophage tail fibers |
| title_full | Functional domains of Acinetobacter bacteriophage tail fibers |
| title_fullStr | Functional domains of Acinetobacter bacteriophage tail fibers |
| title_full_unstemmed | Functional domains of Acinetobacter bacteriophage tail fibers |
| title_short | Functional domains of Acinetobacter bacteriophage tail fibers |
| title_sort | functional domains of acinetobacter bacteriophage tail fibers |
| topic | Acinetobacter bacteriophage protein domains depolymerase pectin lyase tail spike |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2024.1230997/full |
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