Publicação
A new endolysin to combat Helicobacter pylori infections and gastric cancer prevention
| Resumo: | Helicobacter pylori is a Gram-negative microaerobic bacterium. This bacterium causes the most common chronic infection worldwide, affecting more than half of the world’s population, and is therefore considered the major human pathogen. H. pylori infections are difficult to cure, owing to this species rising resistance to standard antibiotic-based therapies. Recently, novel therapies are being developed to treat bacterial infections, such as therapy with bacteriophages (phages) and phage lytic proteins, named endolysins and holins. However, to date, there is minimal information about endolysins in the phage genomes of H. pylori. The main goal of this project is to develop a new therapy based on phage lytic proteins for the treatment of H. pylori infections. Bioinformatics analysis of H. pylori prophage genomes enabled the identification of seven potential lytic proteins coding sequences, which were cloned into pET-28a(+) and expressed in E. coli. Protein expression was only successful for HPy1Rgp29, HPy3RCgp27 and GFP-HPy1Rgp29. The previously reported endolysin ABgp46 from an Acinetobacter phage was also expressed as a positive control. For both assays carried out against H. pylori strain 11507, the positive control in question did not work, so it was not possible to draw any conclusions about the muralytic or antibacterial activity of the proteins considered. The lack of activity of the expressed proteins could be related to the lack of information concerning endolysins on H. pylori phages or the proteins chosen for this work may not be actual endolysins, among others reasons. To better understand the function of these proteins, more extensive work involving for example the fusion of GFP with these proteins might be an interesting approach in future works. In conclusion, while the technology used has great potential, as shown for other pathogens, further research is needed to assess the use of lytic proteins as a treatment for H. pylori infections. |
|---|---|
| Autores principais: | Rocha, Maria Inês Pinto |
| Assunto: | Helicobacter pylori Treatment Bacteriophages Lytic proteins Endolysin Holin Tratamento Bacteriófagos Proteínas líticas Endolisina Holina Engenharia e Tecnologia::Engenharia Médica |
| Ano: | 2023 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| _version_ | 1867439728858497024 |
|---|---|
| author | Rocha, Maria Inês Pinto |
| author_facet | Rocha, Maria Inês Pinto |
| author_role | author |
| contributor_name_str_mv | Melo, Luís Daniel Rodrigues Santos, Sílvio Roberto Branco RepositóriUM - Universidade do Minho |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Rocha, Maria Inês Pinto\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Melo, Luís Daniel Rodrigues Santos, Sílvio Roberto Branco RepositóriUM - Universidade do Minho |
| datacite.creators.creator.creatorName.fl_str_mv | Rocha, Maria Inês Pinto |
| datacite.date.Accepted.fl_str_mv | 2023-12-21T00:00:00Z |
| datacite.date.available.fl_str_mv | 2025-01-15T14:27:21Z |
| datacite.date.embargoed.fl_str_mv | 2025-01-15T14:27:21Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | Helicobacter pylori Treatment Bacteriophages Lytic proteins Endolysin Holin Tratamento Bacteriófagos Proteínas líticas Endolisina Holina Engenharia e Tecnologia::Engenharia Médica |
| datacite.titles.title.fl_str_mv | A new endolysin to combat Helicobacter pylori infections and gastric cancer prevention |
| dc.contributor.none.fl_str_mv | Melo, Luís Daniel Rodrigues Santos, Sílvio Roberto Branco RepositóriUM - Universidade do Minho |
| dc.creator.none.fl_str_mv | Rocha, Maria Inês Pinto |
| dc.date.Accepted.fl_str_mv | 2023-12-21T00:00:00Z |
| dc.date.available.fl_str_mv | 2025-01-15T14:27:21Z |
| dc.date.embargoed.fl_str_mv | 2025-01-15T14:27:21Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | https://hdl.handle.net/1822/94466 |
| dc.language.none.fl_str_mv | eng |
| dc.rights.cclincense.fl_str_mv | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.rights.rights.copyright.fl_str_mv | openAccess |
| dc.subject.none.fl_str_mv | Helicobacter pylori Treatment Bacteriophages Lytic proteins Endolysin Holin Tratamento Bacteriófagos Proteínas líticas Endolisina Holina Engenharia e Tecnologia::Engenharia Médica |
| dc.title.fl_str_mv | A new endolysin to combat Helicobacter pylori infections and gastric cancer prevention |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_bdcc |
| description | Helicobacter pylori is a Gram-negative microaerobic bacterium. This bacterium causes the most common chronic infection worldwide, affecting more than half of the world’s population, and is therefore considered the major human pathogen. H. pylori infections are difficult to cure, owing to this species rising resistance to standard antibiotic-based therapies. Recently, novel therapies are being developed to treat bacterial infections, such as therapy with bacteriophages (phages) and phage lytic proteins, named endolysins and holins. However, to date, there is minimal information about endolysins in the phage genomes of H. pylori. The main goal of this project is to develop a new therapy based on phage lytic proteins for the treatment of H. pylori infections. Bioinformatics analysis of H. pylori prophage genomes enabled the identification of seven potential lytic proteins coding sequences, which were cloned into pET-28a(+) and expressed in E. coli. Protein expression was only successful for HPy1Rgp29, HPy3RCgp27 and GFP-HPy1Rgp29. The previously reported endolysin ABgp46 from an Acinetobacter phage was also expressed as a positive control. For both assays carried out against H. pylori strain 11507, the positive control in question did not work, so it was not possible to draw any conclusions about the muralytic or antibacterial activity of the proteins considered. The lack of activity of the expressed proteins could be related to the lack of information concerning endolysins on H. pylori phages or the proteins chosen for this work may not be actual endolysins, among others reasons. To better understand the function of these proteins, more extensive work involving for example the fusion of GFP with these proteins might be an interesting approach in future works. In conclusion, while the technology used has great potential, as shown for other pathogens, further research is needed to assess the use of lytic proteins as a treatment for H. pylori infections. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | masterThesis |
| fulltext.url.fl_str_mv | https://repositorium.uminho.pt/bitstreams/348043cc-0156-4ff6-a1fb-ae64b68cae26/download |
| id | rum_df08e1ad4684ceddc97fb54e2b04870e |
| identifier.url.fl_str_mv | https://hdl.handle.net/1822/94466 |
| instacron_str | repositorium |
| institution | Universidade do Minho |
| instname_str | Universidade do Minho |
| language | eng |
| network_acronym_str | rum |
| network_name_str | RepositóriUM - Universidade do Minho |
| oai_identifier_str | oai:repositorium.uminho.pt:1822/94466 |
| organization_str_mv | urn:organizationAcronym:repositorium |
| person_str_mv | Rocha, Maria Inês Pinto |
| publishDate | 2023 |
| reponame_str | RepositóriUM - Universidade do Minho |
| repository_id_str | urn:repositoryAcronym:rum |
| service_str_mv | urn:repositoryAcronym:rum |
| spelling | engporHelicobacter pylori is a Gram-negative microaerobic bacterium. This bacterium causes the most common chronic infection worldwide, affecting more than half of the world’s population, and is therefore considered the major human pathogen. H. pylori infections are difficult to cure, owing to this species rising resistance to standard antibiotic-based therapies. Recently, novel therapies are being developed to treat bacterial infections, such as therapy with bacteriophages (phages) and phage lytic proteins, named endolysins and holins. However, to date, there is minimal information about endolysins in the phage genomes of H. pylori. The main goal of this project is to develop a new therapy based on phage lytic proteins for the treatment of H. pylori infections. Bioinformatics analysis of H. pylori prophage genomes enabled the identification of seven potential lytic proteins coding sequences, which were cloned into pET-28a(+) and expressed in E. coli. Protein expression was only successful for HPy1Rgp29, HPy3RCgp27 and GFP-HPy1Rgp29. The previously reported endolysin ABgp46 from an Acinetobacter phage was also expressed as a positive control. For both assays carried out against H. pylori strain 11507, the positive control in question did not work, so it was not possible to draw any conclusions about the muralytic or antibacterial activity of the proteins considered. The lack of activity of the expressed proteins could be related to the lack of information concerning endolysins on H. pylori phages or the proteins chosen for this work may not be actual endolysins, among others reasons. To better understand the function of these proteins, more extensive work involving for example the fusion of GFP with these proteins might be an interesting approach in future works. In conclusion, while the technology used has great potential, as shown for other pathogens, further research is needed to assess the use of lytic proteins as a treatment for H. pylori infections.application/pdfporA new endolysin to combat Helicobacter pylori infections and gastric cancer preventionRocha, Maria Inês PintoMelo, Luís Daniel RodriguesSantos, Sílvio Roberto BrancoHostingInstitutionOrganizationalRepositóriUM - Universidade do Minhoe-mailmailto:repositorium@usdb.uminho.ptrepositorium@usdb.uminho.ptTID2037075592025-01-15T14:27:21Z2023-12-212023-102023-12-21T00:00:00ZHandlehttps://hdl.handle.net/1822/94466http://purl.org/coar/access_right/c_abf2open accessHelicobacter pyloriTreatmentBacteriophagesLytic proteinsEndolysinHolinTratamentoBacteriófagosProteínas líticasEndolisinaHolinahttp://www.oecd.org/science/inno/38235147.pdfFields of Science and Technology (FOS)Engenharia e Tecnologia::Engenharia Médica12713733 bytesliteraturehttp://purl.org/coar/resource_type/c_bdccmaster thesis2023-12-21http://creativecommons.org/licenses/by-nc-nd/4.0/openAccesshttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://repositorium.uminho.pt/bitstreams/348043cc-0156-4ff6-a1fb-ae64b68cae26/download |
| spellingShingle | A new endolysin to combat Helicobacter pylori infections and gastric cancer prevention Rocha, Maria Inês Pinto Helicobacter pylori Treatment Bacteriophages Lytic proteins Endolysin Holin Tratamento Bacteriófagos Proteínas líticas Endolisina Holina Engenharia e Tecnologia::Engenharia Médica |
| status | SINGLETON |
| subject.fl_str_mv | Helicobacter pylori Treatment Bacteriophages Lytic proteins Endolysin Holin Tratamento Bacteriófagos Proteínas líticas Endolisina Holina |
| subject.other.fl_str_mv | Engenharia e Tecnologia::Engenharia Médica |
| title | A new endolysin to combat Helicobacter pylori infections and gastric cancer prevention |
| title_full | A new endolysin to combat Helicobacter pylori infections and gastric cancer prevention |
| title_fullStr | A new endolysin to combat Helicobacter pylori infections and gastric cancer prevention |
| title_full_unstemmed | A new endolysin to combat Helicobacter pylori infections and gastric cancer prevention |
| title_short | A new endolysin to combat Helicobacter pylori infections and gastric cancer prevention |
| title_sort | A new endolysin to combat Helicobacter pylori infections and gastric cancer prevention |
| topic | Helicobacter pylori Treatment Bacteriophages Lytic proteins Endolysin Holin Tratamento Bacteriófagos Proteínas líticas Endolisina Holina Engenharia e Tecnologia::Engenharia Médica |
| topic_facet | Helicobacter pylori Treatment Bacteriophages Lytic proteins Endolysin Holin Tratamento Bacteriófagos Proteínas líticas Endolisina Holina Engenharia e Tecnologia::Engenharia Médica |
| url | https://hdl.handle.net/1822/94466 |
| visible | 1 |