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Antimicrobial activity of prophage endolysins against critical Enterobacteriaceae antibiotic-resistant bacteria

2023-12-30Journal article Open access
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dc.contributor.authorGonçalves, Tiago
dc.contributor.authorMarques, Andreia T.
dc.contributor.authorManageiro, Vera
dc.contributor.authorTanoeiro, Luis
dc.contributor.authorVital, Joana S.
dc.contributor.authorDuarte, Aida
dc.contributor.authorVítor, Jorge M.B.
dc.contributor.authorCaniça, Manuela
dc.contributor.authorGaspar, Maria Manuela
dc.contributor.authorVale, Filipa F.
dc.date.accessioned2024-01-25T12:33:26Z
dc.date.available2024-01-25T12:33:26Z
dc.date.issued2023-12-30
dc.description.abstractEnterobacteriaceae species are part of the 2017 World Health Organization antibiotic-resistant priority pathogens list for development of novel medicines. Multidrug-resistant Klebsiella pneumoniae is an increasing threat to public health and has become a relevant human pathogen involved in life-threatening infections. Phage therapy involves the use of phages or their lytic endolysins as bioagents for the treatment of bacterial infectious diseases. Gram-negative bacteria have an outer membrane, making difficult the access of endolysins to the peptidoglycan. Here, three endolysins from prophages infecting three distinct Enterobacterales species, Kp2948-Lys from K. pneumoniae, Ps3418-Lys from Providencia stuartii, and Kaer26608-Lys from Klebsiella aerogenes, were purified and exhibited antibacterial activity against their specific bacterium species verified by zymogram assays. These three endolysins were successfully associated to liposomes composed of dimyristoyl phosphatidyl choline (DMPC), dioleoyl phosphatidyl ethanolamine (DOPE) and cholesteryl hemisuccinate (CHEMS) at a molar ratio (4:4:2), with an encapsulation efficiency ranging from 24 to 27%. Endolysins encapsulated in liposomes resulted in higher antibacterial activity compared to the respective endolysin in the free form, suggesting that the liposome-mediated delivery system enhances fusion with outer membrane and delivery of endolysins to the target peptidoglycan. Obtained results suggest that Kp2948-Lys appears to be specific for K. pneumoniae, while Ps3418-Lys and Kaer26608-Lys appear to have a broader antibacterial spectrum. Endolysins incorporated in liposomes constitute a promising weapon, applicable in the several dimensions (human, animals and environment) of the One Health approach, against multidrug-resistant Enterobacteriaceae.pt_PT
dc.description.sponsorshipF.F.V. was funded by Fundação para a Ciência e a Tecnologia (FCT) through a project grant (PTDC/BTM-SAL/28978/2017) that supported this work. The work is partially supported by National funds from FCT, projects UIDB/04138/2020, UIDP/04138/2020, UIDB/00211/2020 and UIDB/04046/2020 (DOI https://doi.org/10.54499/UIDB/0404 6/2020)pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationInt J Pharm. 2023 Dec 30:651:123758. doi: 10.1016/j.ijpharm.2023.123758. Online ahead of print.pt_PT
dc.identifier.doi10.1016/j.ijpharm.2023.123758pt_PT
dc.identifier.issn0378-5173
dc.identifier.urihttp://hdl.handle.net/10400.18/8983
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationPhage-Enzybiotic: dealing with critical pathogenic antibiotic-resistant bacteria
dc.relationResearch Institute for Medicines
dc.relationResearch Institute for Medicines
dc.relationCenter for the Study of Animal Science
dc.relationBiosystems and Integrative Sciences Institute
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/pii/S0378517323011808?via%3Dihubpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectAntibiotic Resistancept_PT
dc.subjectEndolysinpt_PT
dc.subjectEndolysinpt_PT
dc.subjectEnterobacteriaceaept_PT
dc.subjectKlebsiella pneumoniaept_PT
dc.subjectLiposomept_PT
dc.subjectPhage Therapypt_PT
dc.subjectResistência aos Antimicrobianospt_PT
dc.titleAntimicrobial activity of prophage endolysins against critical Enterobacteriaceae antibiotic-resistant bacteriapt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitlePhage-Enzybiotic: dealing with critical pathogenic antibiotic-resistant bacteria
oaire.awardTitleResearch Institute for Medicines
oaire.awardTitleResearch Institute for Medicines
oaire.awardTitleCenter for the Study of Animal Science
oaire.awardTitleBiosystems and Integrative Sciences Institute
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FBTM-SAL%2F28978%2F2017/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04138%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F04138%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F00211%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04046%2F2020/PT
oaire.citation.startPage123758pt_PT
oaire.citation.titleInternational Journal of Pharmaceuticspt_PT
oaire.citation.volume651pt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.embargofctAcesso de acordo com a página web da revista.pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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