Antimicrobial activity of Mycobacteriophage D29 Lysin B during Mycobacterium ulcerans infection

Detalhes bibliográficos
Autor(a) principal: Fraga, Alexandra G.
Data de Publicação: 2019
Outros Autores: Branquinho, Gabriela Alexandra Trigo, Murthy, Ramya K., Akhtar, Shamim, Hebbur, Madhavi, Pacheco, Ana Rita, Dominguez, Juan, Silva-Gomes, Rita, Gonçalves, Carine M., Oliveira, Hugo Alexandre Mendes, Castro, António G., Sharma, Umender, Azeredo, Joana, Pedrosa, Jorge
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Texto Completo: http://hdl.handle.net/1822/61425
Resumo: Buruli Ulcer (BU) is a necrotizing skin disease caused by Mycobacterium ulcerans. Although the current antibiotic treatment for BU is effective, daily administrations for a prolonged period of time, combined with potential risk of severe side effects, negatively impact on patient adherence. In that sense, we tested the efficacy of an alternative strategy based on Lysin B (LysB), a phage encoded lipolytic enzyme that degrades the mycolylarabinogalactan-peptidoglycan complex present in the mycobacterial cell wall. In this study, we show that LysB not only displays lytic activity against M. ulcerans isolates in vitro, but also leads to a decrease of M. ulcerans proliferation in infected mouse footpads. These findings highlight the potential use of lysins as a novel therapeutic approach against this neglected tropical disease.
id RCAP_856f01eadafed78111aa979069542e24
oai_identifier_str oai:repositorium.sdum.uminho.pt:1822/61425
network_acronym_str RCAP
network_name_str Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
repository_id_str https://opendoar.ac.uk/repository/7160
spelling Antimicrobial activity of Mycobacteriophage D29 Lysin B during Mycobacterium ulcerans infectionCiências Médicas::Ciências da SaúdeScience & TechnologyBuruli Ulcer (BU) is a necrotizing skin disease caused by Mycobacterium ulcerans. Although the current antibiotic treatment for BU is effective, daily administrations for a prolonged period of time, combined with potential risk of severe side effects, negatively impact on patient adherence. In that sense, we tested the efficacy of an alternative strategy based on Lysin B (LysB), a phage encoded lipolytic enzyme that degrades the mycolylarabinogalactan-peptidoglycan complex present in the mycobacterial cell wall. In this study, we show that LysB not only displays lytic activity against M. ulcerans isolates in vitro, but also leads to a decrease of M. ulcerans proliferation in infected mouse footpads. These findings highlight the potential use of lysins as a novel therapeutic approach against this neglected tropical disease.The projectwas developed withinthescopeof the projectsNORTE-01-0145-FEDER-000013and NORTE-01-0145-FEDER-000023,supported by the Northern Portugal Regional Operational Programme (NORTE2020),under the Portugal2020 Partnership Agreement through FEDER.This work was also supported by BioTecNorte operation (NORTE-01-0145-FEDER -000004) funded by the European Regional Development Fund under the scope of NORTE2020.This study was supportedby the Portuguese Foundation for Scienceand Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit; the Competitiveness Factors Operational Programme (COMPETE 2020) projectsPOCI-01-0145-FEDER-006684 and POCI-01-0145-FEDER-007038; and the project PTDC/BBB-BSS/6471/2014 (POCI-01-0145-FEDER-016678). This study was also supported by Infect-ERA grant Infect-ERA/0002/2015 :BU_SPONT_HEAL. AGF,GT, and HO wouldlike to acknowledge FCT for the individual fellowships SFRH/BPD/112903/2015, SFRH/BPD/64032/2009,and SFRH/BPD/111653/2015,respectively. CMG received an individual QRENfellowship (UMINHO/BPD/15/2014). GangaGen acknowledges CSIR/ OSDD,Govt of India,for funding this project.The funders had no role in study design,data collection and analysis, decision to publish, or preparation of the manuscriptinfo:eu-repo/semantics/publishedVersionPublic Library of ScienceUniversidade do MinhoFraga, Alexandra G.Branquinho, Gabriela Alexandra TrigoMurthy, Ramya K.Akhtar, ShamimHebbur, MadhaviPacheco, Ana RitaDominguez, JuanSilva-Gomes, RitaGonçalves, Carine M.Oliveira, Hugo Alexandre MendesCastro, António G.Sharma, UmenderAzeredo, JoanaPedrosa, Jorge2019-08-192019-08-19T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/61425engFraga, Alexandra G.; Branquinho, Gabriela Alexandra Trigo; Murthy, Ramya K.; Akhtar, Shamim; Hebbur, Madhavi; Pacheco, Ana Rita; Dominguez, Juan; Silva-Gomes, Rita; Gonçalves, Carine M.; Oliveira, Hugo; Castro, António G.; Sharma, Umender; Azeredo, Joana; Pedrosa, Jorge, Antimicrobial activity of Mycobacteriophage D29 Lysin B during Mycobacterium ulcerans infection. PLoS Neglected Tropical Diseases, 13(8), 1-17, 20191935-27271935-273510.1371/journal.pntd.000711331425525http://journals.plos.org/plosntds/info:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2024-05-11T06:10:32Zoai:repositorium.sdum.uminho.pt:1822/61425Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-28T15:43:29.352681Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
dc.title.none.fl_str_mv Antimicrobial activity of Mycobacteriophage D29 Lysin B during Mycobacterium ulcerans infection
title Antimicrobial activity of Mycobacteriophage D29 Lysin B during Mycobacterium ulcerans infection
spellingShingle Antimicrobial activity of Mycobacteriophage D29 Lysin B during Mycobacterium ulcerans infection
Fraga, Alexandra G.
Ciências Médicas::Ciências da Saúde
Science & Technology
title_short Antimicrobial activity of Mycobacteriophage D29 Lysin B during Mycobacterium ulcerans infection
title_full Antimicrobial activity of Mycobacteriophage D29 Lysin B during Mycobacterium ulcerans infection
title_fullStr Antimicrobial activity of Mycobacteriophage D29 Lysin B during Mycobacterium ulcerans infection
title_full_unstemmed Antimicrobial activity of Mycobacteriophage D29 Lysin B during Mycobacterium ulcerans infection
title_sort Antimicrobial activity of Mycobacteriophage D29 Lysin B during Mycobacterium ulcerans infection
author Fraga, Alexandra G.
author_facet Fraga, Alexandra G.
Branquinho, Gabriela Alexandra Trigo
Murthy, Ramya K.
Akhtar, Shamim
Hebbur, Madhavi
Pacheco, Ana Rita
Dominguez, Juan
Silva-Gomes, Rita
Gonçalves, Carine M.
Oliveira, Hugo Alexandre Mendes
Castro, António G.
Sharma, Umender
Azeredo, Joana
Pedrosa, Jorge
author_role author
author2 Branquinho, Gabriela Alexandra Trigo
Murthy, Ramya K.
Akhtar, Shamim
Hebbur, Madhavi
Pacheco, Ana Rita
Dominguez, Juan
Silva-Gomes, Rita
Gonçalves, Carine M.
Oliveira, Hugo Alexandre Mendes
Castro, António G.
Sharma, Umender
Azeredo, Joana
Pedrosa, Jorge
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade do Minho
dc.contributor.author.fl_str_mv Fraga, Alexandra G.
Branquinho, Gabriela Alexandra Trigo
Murthy, Ramya K.
Akhtar, Shamim
Hebbur, Madhavi
Pacheco, Ana Rita
Dominguez, Juan
Silva-Gomes, Rita
Gonçalves, Carine M.
Oliveira, Hugo Alexandre Mendes
Castro, António G.
Sharma, Umender
Azeredo, Joana
Pedrosa, Jorge
dc.subject.por.fl_str_mv Ciências Médicas::Ciências da Saúde
Science & Technology
topic Ciências Médicas::Ciências da Saúde
Science & Technology
description Buruli Ulcer (BU) is a necrotizing skin disease caused by Mycobacterium ulcerans. Although the current antibiotic treatment for BU is effective, daily administrations for a prolonged period of time, combined with potential risk of severe side effects, negatively impact on patient adherence. In that sense, we tested the efficacy of an alternative strategy based on Lysin B (LysB), a phage encoded lipolytic enzyme that degrades the mycolylarabinogalactan-peptidoglycan complex present in the mycobacterial cell wall. In this study, we show that LysB not only displays lytic activity against M. ulcerans isolates in vitro, but also leads to a decrease of M. ulcerans proliferation in infected mouse footpads. These findings highlight the potential use of lysins as a novel therapeutic approach against this neglected tropical disease.
publishDate 2019
dc.date.none.fl_str_mv 2019-08-19
2019-08-19T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/1822/61425
url http://hdl.handle.net/1822/61425
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Fraga, Alexandra G.; Branquinho, Gabriela Alexandra Trigo; Murthy, Ramya K.; Akhtar, Shamim; Hebbur, Madhavi; Pacheco, Ana Rita; Dominguez, Juan; Silva-Gomes, Rita; Gonçalves, Carine M.; Oliveira, Hugo; Castro, António G.; Sharma, Umender; Azeredo, Joana; Pedrosa, Jorge, Antimicrobial activity of Mycobacteriophage D29 Lysin B during Mycobacterium ulcerans infection. PLoS Neglected Tropical Diseases, 13(8), 1-17, 2019
1935-2727
1935-2735
10.1371/journal.pntd.0007113
31425525
http://journals.plos.org/plosntds/
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron:RCAAP
instname_str FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron_str RCAAP
institution RCAAP
reponame_str Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
collection Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
repository.name.fl_str_mv Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
repository.mail.fl_str_mv info@rcaap.pt
_version_ 1833595501314834432