Publication
Insights into macrolide resistance in Arcobacter butzleri: potential resistance mechanisms and impact on bacterial fitness and virulence
| dc.contributor.author | Couto, Francisca | |
| dc.contributor.author | Martins, Inês | |
| dc.contributor.author | Vale, Filipa | |
| dc.contributor.author | Domingues, Fernanda | |
| dc.contributor.author | Oleastro, Mónica | |
| dc.contributor.author | Ferreira, Susana | |
| dc.date.accessioned | 2025-04-02T13:38:45Z | |
| dc.date.available | 2025-04-02T13:38:45Z | |
| dc.date.issued | 2024-10-01 | |
| dc.description.abstract | Background: Macrolides are recommended for treating the emerging enteropathogen Arcobacter butzleri; nonetheless, this bacterium often exhibits highly variable resistance rates, and the mechanisms behind this resistance phenotype remain largely unexplored. Objectives: To understand the phenotypic and genotypic consequences associated with the acquisition of erythromycin resistance in A. butzleri, as well as the effects on the fitness of this species. Methods: Resistant strains resulting from spontaneous mutations and adaptive laboratory evolution under increasing erythromycin concentrations were examined regarding their cross-resistance and collateral susceptibility profiles. Genetic causes of phenotypic antibiotic resistance were analysed by sequencing and bioinformatics, with functional correlation through ethidium bromide accumulation assays. Growth profiles in the presence and absence of erythromycin, motility and biofilm formation abilities were assessed to detect potential changes in fitness and virulence. Results: Clones from spontaneous mutation rate evolution demonstrated decreased susceptibility to erythromycin and other classes of antibiotics, associated with mutations in the transcriptional repressor areR, causing overexpression of the AreABC efflux pump. In turn, WGS analysis of the evolved strain showed additional mutations in the ribosomal proteins L4 and L22 and in the areR gene. Furthermore, the acquisition of macrolide resistance altered A. butzleri virulence and entailed a high biological cost. Conclusions: The findings of this study have proved that efflux activity contributes synergistically with mutations in the ribosomal proteins L4 and L22 to A. butzleri's high-level macrolide resistance. The results further suggest an impact on the bacterial physiology and virulence, with the increased fitness cost justifying the low worldwide prevalence of high-level resistant circulating strains. | eng |
| dc.description.sponsorship | This work was supported by funds from the CICS-UBI base funding (https://doi.org/10.54499/UIDB/00709/2020) and programme funding (https://doi.org/10.54499/UIDP/00709/2020) with national funds registered in the budget of the Foundation for Science and Technology. | |
| dc.identifier.citation | J Antimicrob Chemother. 2024 Oct 1;79(10):2708-2717. doi: 10.1093/jac/dkae287 | |
| dc.identifier.doi | 10.1093/jac/dkae287 | |
| dc.identifier.issn | 0305-7453 | |
| dc.identifier.pmid | 39159041 | |
| dc.identifier.uri | http://hdl.handle.net/10400.18/10467 | |
| dc.language.iso | eng | |
| dc.peerreviewed | yes | |
| dc.publisher | Oxford University Press | |
| dc.relation | Health Sciences Research Centre | |
| dc.relation | Health Sciences Research Centre | |
| dc.relation.hasversion | https://academic.oup.com/jac/article/79/10/2708/7736047 | |
| dc.rights.uri | N/A | |
| dc.subject | Arcobacter butzleri | |
| dc.subject | A. butzleri | |
| dc.subject | AMR | |
| dc.subject | Macrolides | |
| dc.subject | Efflux Pumps | |
| dc.subject | Infecções Gastrointestinais | |
| dc.title | Insights into macrolide resistance in Arcobacter butzleri: potential resistance mechanisms and impact on bacterial fitness and virulence | eng |
| dc.type | clinical study | |
| dspace.entity.type | Publication | |
| oaire.awardTitle | Health Sciences Research Centre | |
| oaire.awardTitle | Health Sciences Research Centre | |
| oaire.awardURI | info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F00709%2F2020/PT | |
| oaire.awardURI | info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F00709%2F2020/PT | |
| oaire.citation.endPage | 2717 | |
| oaire.citation.issue | 10 | |
| oaire.citation.startPage | 2708 | |
| oaire.citation.title | Journal of Antimicrobial Chemotherapy | |
| oaire.citation.volume | 79 | |
| oaire.fundingStream | 6817 - DCRRNI ID | |
| oaire.fundingStream | 6817 - DCRRNI ID | |
| oaire.version | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |
| project.funder.identifier | http://doi.org/10.13039/501100001871 | |
| project.funder.identifier | http://doi.org/10.13039/501100001871 | |
| project.funder.name | Fundação para a Ciência e a Tecnologia | |
| project.funder.name | Fundação para a Ciência e a Tecnologia | |
| relation.isProjectOfPublication | ced21566-cfde-4640-afff-0536a07c1f8f | |
| relation.isProjectOfPublication | e0fbaa7c-391a-479d-9bcf-efb7997d4004 | |
| relation.isProjectOfPublication.latestForDiscovery | ced21566-cfde-4640-afff-0536a07c1f8f |