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BlaGES-6 producing Pseudomonas aeruginosa ST235 is involved in resistance to different β-lactams

2025-08-05Artigo científico Acesso aberto
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dc.contributor.authorde Sousa, Telma
dc.contributor.authorMachado, Sandro
dc.contributor.authorCarvalho, Márcia
dc.contributor.authorCaniça, Manuela
dc.contributor.authorRamos, Miguel J.N.
dc.contributor.authorSantos, Daniela
dc.contributor.authorBeyrouthy, Racha
dc.contributor.authorBonnet, Richard
dc.contributor.authorHébraud, Michel
dc.contributor.authorGomes, João Paulo
dc.contributor.authorIgrejas, Gilberto
dc.contributor.authorPoeta, Patrícia
dc.date.accessioned2026-02-05T11:06:36Z
dc.date.available2026-02-05T11:06:36Z
dc.date.issued2025-08-05
dc.description.abstractMultidrug resistance in Pseudomonas aeruginosa, particularly resistance to carbapenem, represents a major challenge for public health. This study investigated resistance mechanisms in three P. aeruginosa isolates: HU63 (blaGES-6 carbapenemase-positive), HU141 (carbapenem-resistant without carbapenemase), and PAO1 (control). Genomic analysis revealed distinct sequence types (ST235 for HU63, ST253 for HU141) and chromosomal integration of resistance genes. HU63 harbored diverse resistance mechanisms, including β-lactamases (bla, bla, bla) and efflux pumps. Minimum inhibitory concentration assays demonstrated HU63's resistance to all β-lactams tested (meropenem, imipenem-cilastatin, ceftazidime, piperacillin-tazobactam), while HU141 remained susceptible except to cefoxitin and cloxacillin. Time-kill assays revealed tolerance phenotypes, with HU63 showing regrowth after 8-24 h despite initial reductions in bacterial density. Gene expression varied significantlydepending on the antibiotic and the isolate. The HU63 isolate (GES-6 positive) stands out for its marked induction of bla in all the antibiotics tested, contributing to its resistance to carbapenems and broad-spectrum cephalosporins. These expression profiles corroborate the classic molecular mechanisms of resistance: regulation of entry pores (oprD), activation of efflux pumps (mexA) and production of β-lactamases (bla, ampC) adapted to each situation. These findings underscore the multifactorial nature of resistance in Carbapenem-resistant Pseudomonas aeruginosa (CRPA), combining enzymatic inactivation, efflux, and genetic adaptability. The study emphasizes the urgent need for genomic surveillance to track high-risk clones and develop therapies targeting tolerance mechanisms alongside traditional resistance.eng
dc.description.abstractHighlights: -GES-6-producing P. aeruginosa ST235 shows resistance to all tested β-lactams. -Time-kill assays reveal antibiotic tolerance with regrowth after initial suppression. -BlaGES-6 is significantly induced by ceftazidime, enhancing resistance expression. -Genomic surveillance is vital to track high-risk clones like ST235 in clinical settings.eng
dc.description.sponsorshipThis research was funded by FCT (Fundação para a Ciência e a Tecnologia) related toa Ph.D. grant through the reference 2020.05332.BD, and the projects UI/00772 and LAP/0059/2020. This work received support and help from FCT/MCTES (LA/P/0008/2020 DOI 10.54499/LA/P/0008/2020, UIDP/50006/2020 DOI 10.54499/UIDP/50006/2020 and UIDB/50006/2020 DOI 10.54499/UIDB/50006/2020), through national funds.Márcia Carvalho research was supported by national funds provided by the Portuguese Foundation for the Science and Technology (FCT) under the projects UIDB/04033/2020 (https://doi.org/10.54499/UIDB/04033/2020) and 2020.03997. CEECIND/CP1598/CT0001 (https://doi.org/10.54499/2020.03997. CEECIND/CP1598/CT0001).
dc.identifier.citationMicrob Pathog. 2025 Nov:208:107962. doi: 10.1016/j.micpath.2025.107962. Epub 2025 Aug 5
dc.identifier.doi10.1016/j.micpath.2025.107962
dc.identifier.eissn1096-1208
dc.identifier.issn0882-4010
dc.identifier.pmid40774566
dc.identifier.urihttp://hdl.handle.net/10400.18/10811
dc.language.isoeng
dc.peerreviewedyes
dc.publisherElsevier
dc.relationAssociate Laboratory for Animal and Veterinary Sciences
dc.relationCentre for the Research and Technology of Agro-Environmental and Biological Sciences
dc.relationEpidemiology of colistin-resistant Pseudomonas aeruginosa from humans, animals and ecosystems: a one health approach using omics tools OMIC4COLPA
dc.relationUIDB/04033/2020
dc.relation.hasversionhttps://www.sciencedirect.com/science/article/pii/S0882401025006874?via%3Dihub
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectAntimicrobial Resistance
dc.subjectGenomic Approach
dc.subjectMultidrug Resistance
dc.subjectP. aeruginosa
dc.subjectβ-lactamases
dc.subjectResistência aos Antimicrobianos
dc.titleBlaGES-6 producing Pseudomonas aeruginosa ST235 is involved in resistance to different β-lactamseng
dc.typejournal article
dcterms.referenceshttps://ars.els-cdn.com/content/image/1-s2.0-S0882401025006874-mmc1.docx
dspace.entity.typePublication
oaire.awardTitleAssociate Laboratory for Animal and Veterinary Sciences
oaire.awardTitleCentre for the Research and Technology of Agro-Environmental and Biological Sciences
oaire.awardTitleEpidemiology of colistin-resistant Pseudomonas aeruginosa from humans, animals and ecosystems: a one health approach using omics tools OMIC4COLPA
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/LA%2FP%2F0059%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04033%2F2020/PT
oaire.awardURIhttp://hdl.handle.net/10400.18/10810
oaire.citation.startPage107962
oaire.citation.titleMicrobial Pathogenesis
oaire.citation.volume208
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85
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
relation.isProjectOfPublication93de5af7-dedc-4696-ae11-592584b020a8
relation.isProjectOfPublication5081cbe6-f695-4d42-8494-4d9d84819ea9
relation.isProjectOfPublication74c5cbf6-71c5-423a-8907-2bd20a2e1bd2
relation.isProjectOfPublication.latestForDiscovery93de5af7-dedc-4696-ae11-592584b020a8

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