Cargando…

Unpuzzling Friunavirus-Host Interactions One Piece at a Time: Phage Recognizes Acinetobacter pittii via a New K38 Capsule Depolymerase

Acinetobacter pittii is a species that belong to the Acinetobacter calcoaceticus-baumannii complex, increasingly recognized as major nosocomial bacterial pathogens, often associated with multiple drug-resistances. The capsule surrounding the bacteria represents a main virulence factor, helping cells...

Descripción completa

Detalles Bibliográficos
Autores principales: Domingues, Rita, Barbosa, Ana, Santos, Sílvio B., Pires, Diana Priscila, Save, Jonathan, Resch, Grégory, Azeredo, Joana, Oliveira, Hugo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8614642/
https://www.ncbi.nlm.nih.gov/pubmed/34827242
http://dx.doi.org/10.3390/antibiotics10111304
_version_ 1784603910007160832
author Domingues, Rita
Barbosa, Ana
Santos, Sílvio B.
Pires, Diana Priscila
Save, Jonathan
Resch, Grégory
Azeredo, Joana
Oliveira, Hugo
author_facet Domingues, Rita
Barbosa, Ana
Santos, Sílvio B.
Pires, Diana Priscila
Save, Jonathan
Resch, Grégory
Azeredo, Joana
Oliveira, Hugo
author_sort Domingues, Rita
collection PubMed
description Acinetobacter pittii is a species that belong to the Acinetobacter calcoaceticus-baumannii complex, increasingly recognized as major nosocomial bacterial pathogens, often associated with multiple drug-resistances. The capsule surrounding the bacteria represents a main virulence factor, helping cells avoid phage predation and host immunity. Accordingly, a better understanding of the phage infection mechanisms is required to efficiently develop phage therapy against Acinetobacter of different capsular types. Here, we report the isolation of the novel A. pittii-infecting Fri1-like phage vB_Api_3043-K38 (3043-K38) of the Podoviridae morphotype, from sewage samples. Its 41,580 bp linear double-stranded DNA genome harbours 53 open reading frames and 302 bp of terminal repeats. We show that all studied Acinetobacter Fri1-like viruses have highly similar genomes, which differentiate only at the genes coding for tailspike, likely to adapt to different host receptors. The isolated phage 3043-K38 specifically recognizes an untapped Acinetobacter K38 capsule type via a novel tailspike with K38 depolymerase activity. The recombinant K38 depolymerase region of the tailspike (center-end region) forms a thermostable trimer, and quickly degrades capsules. When the K38 depolymerase is applied to the cells, it makes them resistant to phage predation. Interestingly, while K38 depolymerase treatments do not synergize with antibiotics, it makes bacterial cells highly susceptible to the host serum complement. In summary, we characterized a novel phage-encoded K38 depolymerase, which not only advances our understanding of phage-host interactions, but could also be further explored as a new antibacterial agent against drug-resistant Acinetobacter.
format Online
Article
Text
id pubmed-8614642
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-86146422021-11-26 Unpuzzling Friunavirus-Host Interactions One Piece at a Time: Phage Recognizes Acinetobacter pittii via a New K38 Capsule Depolymerase Domingues, Rita Barbosa, Ana Santos, Sílvio B. Pires, Diana Priscila Save, Jonathan Resch, Grégory Azeredo, Joana Oliveira, Hugo Antibiotics (Basel) Article Acinetobacter pittii is a species that belong to the Acinetobacter calcoaceticus-baumannii complex, increasingly recognized as major nosocomial bacterial pathogens, often associated with multiple drug-resistances. The capsule surrounding the bacteria represents a main virulence factor, helping cells avoid phage predation and host immunity. Accordingly, a better understanding of the phage infection mechanisms is required to efficiently develop phage therapy against Acinetobacter of different capsular types. Here, we report the isolation of the novel A. pittii-infecting Fri1-like phage vB_Api_3043-K38 (3043-K38) of the Podoviridae morphotype, from sewage samples. Its 41,580 bp linear double-stranded DNA genome harbours 53 open reading frames and 302 bp of terminal repeats. We show that all studied Acinetobacter Fri1-like viruses have highly similar genomes, which differentiate only at the genes coding for tailspike, likely to adapt to different host receptors. The isolated phage 3043-K38 specifically recognizes an untapped Acinetobacter K38 capsule type via a novel tailspike with K38 depolymerase activity. The recombinant K38 depolymerase region of the tailspike (center-end region) forms a thermostable trimer, and quickly degrades capsules. When the K38 depolymerase is applied to the cells, it makes them resistant to phage predation. Interestingly, while K38 depolymerase treatments do not synergize with antibiotics, it makes bacterial cells highly susceptible to the host serum complement. In summary, we characterized a novel phage-encoded K38 depolymerase, which not only advances our understanding of phage-host interactions, but could also be further explored as a new antibacterial agent against drug-resistant Acinetobacter. MDPI 2021-10-26 /pmc/articles/PMC8614642/ /pubmed/34827242 http://dx.doi.org/10.3390/antibiotics10111304 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Domingues, Rita
Barbosa, Ana
Santos, Sílvio B.
Pires, Diana Priscila
Save, Jonathan
Resch, Grégory
Azeredo, Joana
Oliveira, Hugo
Unpuzzling Friunavirus-Host Interactions One Piece at a Time: Phage Recognizes Acinetobacter pittii via a New K38 Capsule Depolymerase
title Unpuzzling Friunavirus-Host Interactions One Piece at a Time: Phage Recognizes Acinetobacter pittii via a New K38 Capsule Depolymerase
title_full Unpuzzling Friunavirus-Host Interactions One Piece at a Time: Phage Recognizes Acinetobacter pittii via a New K38 Capsule Depolymerase
title_fullStr Unpuzzling Friunavirus-Host Interactions One Piece at a Time: Phage Recognizes Acinetobacter pittii via a New K38 Capsule Depolymerase
title_full_unstemmed Unpuzzling Friunavirus-Host Interactions One Piece at a Time: Phage Recognizes Acinetobacter pittii via a New K38 Capsule Depolymerase
title_short Unpuzzling Friunavirus-Host Interactions One Piece at a Time: Phage Recognizes Acinetobacter pittii via a New K38 Capsule Depolymerase
title_sort unpuzzling friunavirus-host interactions one piece at a time: phage recognizes acinetobacter pittii via a new k38 capsule depolymerase
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8614642/
https://www.ncbi.nlm.nih.gov/pubmed/34827242
http://dx.doi.org/10.3390/antibiotics10111304
work_keys_str_mv AT dominguesrita unpuzzlingfriunavirushostinteractionsonepieceatatimephagerecognizesacinetobacterpittiiviaanewk38capsuledepolymerase
AT barbosaana unpuzzlingfriunavirushostinteractionsonepieceatatimephagerecognizesacinetobacterpittiiviaanewk38capsuledepolymerase
AT santossilviob unpuzzlingfriunavirushostinteractionsonepieceatatimephagerecognizesacinetobacterpittiiviaanewk38capsuledepolymerase
AT piresdianapriscila unpuzzlingfriunavirushostinteractionsonepieceatatimephagerecognizesacinetobacterpittiiviaanewk38capsuledepolymerase
AT savejonathan unpuzzlingfriunavirushostinteractionsonepieceatatimephagerecognizesacinetobacterpittiiviaanewk38capsuledepolymerase
AT reschgregory unpuzzlingfriunavirushostinteractionsonepieceatatimephagerecognizesacinetobacterpittiiviaanewk38capsuledepolymerase
AT azeredojoana unpuzzlingfriunavirushostinteractionsonepieceatatimephagerecognizesacinetobacterpittiiviaanewk38capsuledepolymerase
AT oliveirahugo unpuzzlingfriunavirushostinteractionsonepieceatatimephagerecognizesacinetobacterpittiiviaanewk38capsuledepolymerase