Involvement of a Phage-Encoded Wzy Protein in the Polymerization of K127 Units To Form the Capsular Polysaccharide of Acinetobacter baumannii Isolate 36-1454
ABSTRACT A comprehensive understanding of capsular polysaccharide (CPS) diversity is critical to implementation of phage therapy to treat panresistant Acinetobacter baumannii infections. Predictions from genome sequences can assist identification of the CPS type but can be complicated if genes outsi...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2022-06-01
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| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.01503-21 |
| _version_ | 1818255482157006848 |
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| author | Nikolay P. Arbatsky Anastasiya A. Kasimova Alexander S. Shashkov Mikhail M. Shneider Anastasiya V. Popova Dmitry A. Shagin Andrey A. Shelenkov Yuliya V. Mikhailova Yurii G. Yanushevich Ruth M. Hall Yuriy A. Knirel Johanna J. Kenyon |
| author_facet | Nikolay P. Arbatsky Anastasiya A. Kasimova Alexander S. Shashkov Mikhail M. Shneider Anastasiya V. Popova Dmitry A. Shagin Andrey A. Shelenkov Yuliya V. Mikhailova Yurii G. Yanushevich Ruth M. Hall Yuriy A. Knirel Johanna J. Kenyon |
| author_sort | Nikolay P. Arbatsky |
| collection | DOAJ |
| description | ABSTRACT A comprehensive understanding of capsular polysaccharide (CPS) diversity is critical to implementation of phage therapy to treat panresistant Acinetobacter baumannii infections. Predictions from genome sequences can assist identification of the CPS type but can be complicated if genes outside the K locus (CPS biosynthesis gene cluster) are involved. Here, the CPS produced by A. baumannii clinical isolate 36-1454 carrying a novel K locus, KL127, was determined and compared to other CPSs. KL127 differs from KL128 in only two of the glycosyltransferase (gtr) genes. The K127 unit in 36-1454 CPS was the pentasaccharide β-d-Glcp-(1→6)-d-β-GalpNAc-(1→6)-α-d-Galp-(1→6)-β-d-Glсp-(1→3)-β-d-GalpNAc in which d-Glcp at position 4 replaces d-Galp in K128, and the glycosyltransferases encoded by the different gtr genes form the surrounding linkages. However, although the KL127 and KL128 gene clusters encode nearly identical Wzy polymerases, the linkages between K units that form the CPS chains are different, i.e., β-d-GalpNAc-(1→3)-d-Galp in 36-1454 (K127) and β-d-GalpNAc-(1→4)-d-Galp in KZ-1093 (K128). The linkage between K127 units in 36-1454 is the same as the K-unit linkage in five known CPS structures, and a gene encoding a Wzy protein related to the Wzy of the corresponding K loci was found encoded in a prophage genome in the 36-1454 chromosome. Closely related Wzy proteins were encoded in unrelated phage in available KL127-carrying genomes. However, a clinical isolate, KZ-1257, carrying KL127 but not the prophage was found, and K127 units in the KZ-1257 CPS were β-d-GalpNAc-(1→4)-d-Galp linked, confirming that WzyKL127 forms this linkage and thus that the phage-encoded WzyPh1 forms the β-d-GalpNAc-(1→3)-d-Galp linkage in 36-1454. IMPORTANCE Bacteriophage therapy is an attractive innovative treatment for infections caused by extensively drug resistant Acinetobacter baumannii, for which there are few effective antibiotic treatments remaining. Capsular polysaccharide (CPS) is a primary receptor for many lytic bacteriophages, and thus knowledge of the chemical structures of CPS produced by the species will underpin the identification of suitable phages for therapeutic cocktails. However, recent research has shown that some isolates carry additional genes outside of the CPS biosynthesis K locus, which can modify the CPS structure. These changes can subsequently alter phage receptor sites and may be a method utilized for natural phage resistance. Hence, it is critical to understand the genetics that drive CPS synthesis and the extent to which genes outside of the K locus can affect the CPS structure. |
| first_indexed | 2024-12-12T17:12:33Z |
| format | Article |
| id | doaj.art-686ef2aeae784cb7b44c910f7b8b8922 |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-12-12T17:12:33Z |
| publishDate | 2022-06-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-686ef2aeae784cb7b44c910f7b8b89222022-12-22T00:17:51ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972022-06-0110310.1128/spectrum.01503-21Involvement of a Phage-Encoded Wzy Protein in the Polymerization of K127 Units To Form the Capsular Polysaccharide of Acinetobacter baumannii Isolate 36-1454Nikolay P. Arbatsky0Anastasiya A. Kasimova1Alexander S. Shashkov2Mikhail M. Shneider3Anastasiya V. Popova4Dmitry A. Shagin5Andrey A. Shelenkov6Yuliya V. Mikhailova7Yurii G. Yanushevich8Ruth M. Hall9Yuriy A. Knirel10Johanna J. Kenyon11N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, RussiaN. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, RussiaN. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, RussiaM. M. Shemyakin & Y. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, RussiaState Research Center for Applied Microbiology and Biotechnology, Obolensk, Moscow, RussiaCentral Scientific Research Institute of Epidemiology, Moscow, RussiaCentral Scientific Research Institute of Epidemiology, Moscow, RussiaCentral Scientific Research Institute of Epidemiology, Moscow, RussiaCentral Scientific Research Institute of Epidemiology, Moscow, RussiaSchool of Life and Environmental Sciences, University of Sydney, Sydney, AustraliaN. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, RussiaCentre for Immunology and Infection Control, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, AustraliaABSTRACT A comprehensive understanding of capsular polysaccharide (CPS) diversity is critical to implementation of phage therapy to treat panresistant Acinetobacter baumannii infections. Predictions from genome sequences can assist identification of the CPS type but can be complicated if genes outside the K locus (CPS biosynthesis gene cluster) are involved. Here, the CPS produced by A. baumannii clinical isolate 36-1454 carrying a novel K locus, KL127, was determined and compared to other CPSs. KL127 differs from KL128 in only two of the glycosyltransferase (gtr) genes. The K127 unit in 36-1454 CPS was the pentasaccharide β-d-Glcp-(1→6)-d-β-GalpNAc-(1→6)-α-d-Galp-(1→6)-β-d-Glсp-(1→3)-β-d-GalpNAc in which d-Glcp at position 4 replaces d-Galp in K128, and the glycosyltransferases encoded by the different gtr genes form the surrounding linkages. However, although the KL127 and KL128 gene clusters encode nearly identical Wzy polymerases, the linkages between K units that form the CPS chains are different, i.e., β-d-GalpNAc-(1→3)-d-Galp in 36-1454 (K127) and β-d-GalpNAc-(1→4)-d-Galp in KZ-1093 (K128). The linkage between K127 units in 36-1454 is the same as the K-unit linkage in five known CPS structures, and a gene encoding a Wzy protein related to the Wzy of the corresponding K loci was found encoded in a prophage genome in the 36-1454 chromosome. Closely related Wzy proteins were encoded in unrelated phage in available KL127-carrying genomes. However, a clinical isolate, KZ-1257, carrying KL127 but not the prophage was found, and K127 units in the KZ-1257 CPS were β-d-GalpNAc-(1→4)-d-Galp linked, confirming that WzyKL127 forms this linkage and thus that the phage-encoded WzyPh1 forms the β-d-GalpNAc-(1→3)-d-Galp linkage in 36-1454. IMPORTANCE Bacteriophage therapy is an attractive innovative treatment for infections caused by extensively drug resistant Acinetobacter baumannii, for which there are few effective antibiotic treatments remaining. Capsular polysaccharide (CPS) is a primary receptor for many lytic bacteriophages, and thus knowledge of the chemical structures of CPS produced by the species will underpin the identification of suitable phages for therapeutic cocktails. However, recent research has shown that some isolates carry additional genes outside of the CPS biosynthesis K locus, which can modify the CPS structure. These changes can subsequently alter phage receptor sites and may be a method utilized for natural phage resistance. Hence, it is critical to understand the genetics that drive CPS synthesis and the extent to which genes outside of the K locus can affect the CPS structure.https://journals.asm.org/doi/10.1128/spectrum.01503-21Acinetobacter baumanniicapsular polysaccharideK locusK127phageWzy polymerase |
| spellingShingle | Nikolay P. Arbatsky Anastasiya A. Kasimova Alexander S. Shashkov Mikhail M. Shneider Anastasiya V. Popova Dmitry A. Shagin Andrey A. Shelenkov Yuliya V. Mikhailova Yurii G. Yanushevich Ruth M. Hall Yuriy A. Knirel Johanna J. Kenyon Involvement of a Phage-Encoded Wzy Protein in the Polymerization of K127 Units To Form the Capsular Polysaccharide of Acinetobacter baumannii Isolate 36-1454 Microbiology Spectrum Acinetobacter baumannii capsular polysaccharide K locus K127 phage Wzy polymerase |
| title | Involvement of a Phage-Encoded Wzy Protein in the Polymerization of K127 Units To Form the Capsular Polysaccharide of Acinetobacter baumannii Isolate 36-1454 |
| title_full | Involvement of a Phage-Encoded Wzy Protein in the Polymerization of K127 Units To Form the Capsular Polysaccharide of Acinetobacter baumannii Isolate 36-1454 |
| title_fullStr | Involvement of a Phage-Encoded Wzy Protein in the Polymerization of K127 Units To Form the Capsular Polysaccharide of Acinetobacter baumannii Isolate 36-1454 |
| title_full_unstemmed | Involvement of a Phage-Encoded Wzy Protein in the Polymerization of K127 Units To Form the Capsular Polysaccharide of Acinetobacter baumannii Isolate 36-1454 |
| title_short | Involvement of a Phage-Encoded Wzy Protein in the Polymerization of K127 Units To Form the Capsular Polysaccharide of Acinetobacter baumannii Isolate 36-1454 |
| title_sort | involvement of a phage encoded wzy protein in the polymerization of k127 units to form the capsular polysaccharide of acinetobacter baumannii isolate 36 1454 |
| topic | Acinetobacter baumannii capsular polysaccharide K locus K127 phage Wzy polymerase |
| url | https://journals.asm.org/doi/10.1128/spectrum.01503-21 |
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