Loss of a Branch Sugar in the Acinetobacter baumannii K3-Type Capsular Polysaccharide Due To Frameshifts in the gtr6 Glycosyltransferase Gene Leads To Susceptibility To Phage APK37.1
ABSTRACT The type of capsular polysaccharide (CPS) on the cell surface of Acinetobacter baumannii can determine the specificity of lytic bacteriophage under consideration for therapeutic use. Here, we report the isolation of a phage on an extensively antibiotic resistant ST2 A. baumannii isolate AB5...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2023-02-01
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| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.03631-22 |
| _version_ | 1811164364534710272 |
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| author | Olga Y. Timoshina Anastasiya A. Kasimova Mikhail M. Shneider Nikolay P. Arbatsky Alexander S. Shashkov Andrey A. Shelenkov Yuliya V. Mikhailova Anastasiya V. Popova Ruth M. Hall Yuriy A. Knirel Johanna J. Kenyon |
| author_facet | Olga Y. Timoshina Anastasiya A. Kasimova Mikhail M. Shneider Nikolay P. Arbatsky Alexander S. Shashkov Andrey A. Shelenkov Yuliya V. Mikhailova Anastasiya V. Popova Ruth M. Hall Yuriy A. Knirel Johanna J. Kenyon |
| author_sort | Olga Y. Timoshina |
| collection | DOAJ |
| description | ABSTRACT The type of capsular polysaccharide (CPS) on the cell surface of Acinetobacter baumannii can determine the specificity of lytic bacteriophage under consideration for therapeutic use. Here, we report the isolation of a phage on an extensively antibiotic resistant ST2 A. baumannii isolate AB5001 that carries the KL3 CPS biosynthesis gene cluster predicting a K3-type CPS. As the phage did not infect isolates carrying KL3 or KL22 and known to produce K3 CPS, the structure of the CPS isolated from A. baumannii AB5001 was determined. AB5001 produced a variant CPS form, K3-v1, that lacks the β-d-GlсpNAc side chain attached to the d-Galp residue in the K3 structure. Inspection of the KL3 sequence in the genomes of AB5001 and other phage-susceptible isolates with a KL3 locus revealed single-base deletions in gtr6, causing loss of the Gtr6 glycosyltransferase that adds the missing d-GlсpNAc side chain to the K3 CPS. Hence, the presence of this sugar profoundly restricts the ability of the phage to digest the CPS. The 41-kb linear double-stranded DNA (dsDNA) phage genome was identical to the genome of a phage isolated on a K37-producing isolate and thus was named APK37.1. APK37.1 also infected isolates carrying KL116. Consistent with this, K3-v1 resembles the K37 and K116 structures. APK37.1 is a Friunavirus belonging to the Autographiviridae family. The phage-encoded tail spike depolymerase DpoAPK37.1 was not closely related to Dpo encoded by other sequenced Friunaviruses, including APK37 and APK116. IMPORTANCE Lytic bacteriophage have potential for the treatment of otherwise untreatable extensively antibiotic-resistant bacteria. For Acinetobacter baumannii, most phage exhibit specificity for the type of capsular polysaccharide (CPS) produced on the cell surface. However, resistance can arise via mutations in CPS genes that abolish this phage receptor. Here, we show that single-base deletions in a CPS gene result in alteration of the final structure rather than deletion of the capsule layer and hence affect the ability of a newly reported podophage to infect strains producing the K3 CPS. |
| first_indexed | 2024-04-10T15:20:22Z |
| format | Article |
| id | doaj.art-5183c3720d6148d2a8d5fe9ed1bbaccc |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-04-10T15:20:22Z |
| publishDate | 2023-02-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-5183c3720d6148d2a8d5fe9ed1bbaccc2023-02-14T14:15:50ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972023-02-0111110.1128/spectrum.03631-22Loss of a Branch Sugar in the Acinetobacter baumannii K3-Type Capsular Polysaccharide Due To Frameshifts in the gtr6 Glycosyltransferase Gene Leads To Susceptibility To Phage APK37.1Olga Y. Timoshina0Anastasiya A. Kasimova1Mikhail M. Shneider2Nikolay P. Arbatsky3Alexander S. Shashkov4Andrey A. Shelenkov5Yuliya V. Mikhailova6Anastasiya V. Popova7Ruth M. Hall8Yuriy A. Knirel9Johanna J. Kenyon10M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, RussiaN. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, RussiaM. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic 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, RussiaCentral Scientific Research Institute of Epidemiology, Moscow, RussiaCentral Scientific Research Institute of Epidemiology, Moscow, RussiaState Research Center for Applied Microbiology and Biotechnology, Obolensk, RussiaSchool of Life and Environmental Science, 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 The type of capsular polysaccharide (CPS) on the cell surface of Acinetobacter baumannii can determine the specificity of lytic bacteriophage under consideration for therapeutic use. Here, we report the isolation of a phage on an extensively antibiotic resistant ST2 A. baumannii isolate AB5001 that carries the KL3 CPS biosynthesis gene cluster predicting a K3-type CPS. As the phage did not infect isolates carrying KL3 or KL22 and known to produce K3 CPS, the structure of the CPS isolated from A. baumannii AB5001 was determined. AB5001 produced a variant CPS form, K3-v1, that lacks the β-d-GlсpNAc side chain attached to the d-Galp residue in the K3 structure. Inspection of the KL3 sequence in the genomes of AB5001 and other phage-susceptible isolates with a KL3 locus revealed single-base deletions in gtr6, causing loss of the Gtr6 glycosyltransferase that adds the missing d-GlсpNAc side chain to the K3 CPS. Hence, the presence of this sugar profoundly restricts the ability of the phage to digest the CPS. The 41-kb linear double-stranded DNA (dsDNA) phage genome was identical to the genome of a phage isolated on a K37-producing isolate and thus was named APK37.1. APK37.1 also infected isolates carrying KL116. Consistent with this, K3-v1 resembles the K37 and K116 structures. APK37.1 is a Friunavirus belonging to the Autographiviridae family. The phage-encoded tail spike depolymerase DpoAPK37.1 was not closely related to Dpo encoded by other sequenced Friunaviruses, including APK37 and APK116. IMPORTANCE Lytic bacteriophage have potential for the treatment of otherwise untreatable extensively antibiotic-resistant bacteria. For Acinetobacter baumannii, most phage exhibit specificity for the type of capsular polysaccharide (CPS) produced on the cell surface. However, resistance can arise via mutations in CPS genes that abolish this phage receptor. Here, we show that single-base deletions in a CPS gene result in alteration of the final structure rather than deletion of the capsule layer and hence affect the ability of a newly reported podophage to infect strains producing the K3 CPS.https://journals.asm.org/doi/10.1128/spectrum.03631-22Acinetobacter baumanniicapsular polysaccharideK locusKL3K3-v1APK37.1 |
| spellingShingle | Olga Y. Timoshina Anastasiya A. Kasimova Mikhail M. Shneider Nikolay P. Arbatsky Alexander S. Shashkov Andrey A. Shelenkov Yuliya V. Mikhailova Anastasiya V. Popova Ruth M. Hall Yuriy A. Knirel Johanna J. Kenyon Loss of a Branch Sugar in the Acinetobacter baumannii K3-Type Capsular Polysaccharide Due To Frameshifts in the gtr6 Glycosyltransferase Gene Leads To Susceptibility To Phage APK37.1 Microbiology Spectrum Acinetobacter baumannii capsular polysaccharide K locus KL3 K3-v1 APK37.1 |
| title | Loss of a Branch Sugar in the Acinetobacter baumannii K3-Type Capsular Polysaccharide Due To Frameshifts in the gtr6 Glycosyltransferase Gene Leads To Susceptibility To Phage APK37.1 |
| title_full | Loss of a Branch Sugar in the Acinetobacter baumannii K3-Type Capsular Polysaccharide Due To Frameshifts in the gtr6 Glycosyltransferase Gene Leads To Susceptibility To Phage APK37.1 |
| title_fullStr | Loss of a Branch Sugar in the Acinetobacter baumannii K3-Type Capsular Polysaccharide Due To Frameshifts in the gtr6 Glycosyltransferase Gene Leads To Susceptibility To Phage APK37.1 |
| title_full_unstemmed | Loss of a Branch Sugar in the Acinetobacter baumannii K3-Type Capsular Polysaccharide Due To Frameshifts in the gtr6 Glycosyltransferase Gene Leads To Susceptibility To Phage APK37.1 |
| title_short | Loss of a Branch Sugar in the Acinetobacter baumannii K3-Type Capsular Polysaccharide Due To Frameshifts in the gtr6 Glycosyltransferase Gene Leads To Susceptibility To Phage APK37.1 |
| title_sort | loss of a branch sugar in the acinetobacter baumannii k3 type capsular polysaccharide due to frameshifts in the gtr6 glycosyltransferase gene leads to susceptibility to phage apk37 1 |
| topic | Acinetobacter baumannii capsular polysaccharide K locus KL3 K3-v1 APK37.1 |
| url | https://journals.asm.org/doi/10.1128/spectrum.03631-22 |
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