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Multiomics characterization of methicillin-resistant Staphylococcus aureus (MRSA) isolates with heterogeneous intermediate resistance to vancomycin (hVISA) in Latin America

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dc.contributor.authorCastro, Betsy E.
dc.contributor.authorRíos, Rafael
dc.contributor.authorCarvajal, Lina P.
dc.contributor.authorVargas, Mónica L.
dc.contributor.authorCala, Mónica P.
dc.contributor.authorLeón, Lizeth
dc.contributor.authorHanson, Blake
dc.contributor.authorDinh, An Q.
dc.contributor.authorOrtega-Recalde, Oscar
dc.contributor.authorSeas, Carlos
dc.contributor.authorMunita, José
dc.contributor.authorArias, Cesar A.
dc.contributor.authorRincón, Sandra
dc.contributor.authorReyes, Jinnethe
dc.contributor.authorDíaz, Lorena
dc.date.accessioned2023-07-11T14:57:32Z
dc.date.available2023-07-11T14:57:32Z
dc.date.issued2023
dc.description.abstractBackground: Heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) compromise the clinical efficacy of vancomycin. The hVISA isolates spontaneously produce vancomycin-intermediate Staphylococcus aureus (VISA) cells generated by diverse and intriguing mechanisms. Objective: To characterize the biomolecular profile of clinical hVISA applying genomic, transcriptomic and metabolomic approaches. Methods: 39 hVISA and 305 VSSA and their genomes were included. Core genome-based Bayesian phylogenetic reconstructions were built and alterations in predicted proteins in VISA/hVISA were interrogated. Linear discriminant analysis and a Genome-Wide Association Study were performed. Differentially expressed genes were identified in hVISA-VSSA by RNA-sequencing. The undirected profiles of metabolites were determined by liquid chromatography and hydrophilic interaction in six CC5-MRSA. Results: Genomic relatedness of MRSA associated to hVISA phenotype was not detected. The change Try38 →His in Atl (autolysin) was identified in 92% of the hVISA. We identified SNPs and k-mers associated to hVISA in 11 coding regions with predicted functions in virulence, transport systems, carbohydrate metabolism and tRNA synthesis. Further, capABCDE, sdrD, esaA, esaD, essA and ssaA genes were overexpressed in hVISA, while lacABCDEFG genes were downregulated. Additionally, valine, threonine, leucine tyrosine, FAD and NADH were more abundant in VSSA, while arginine, glycine and betaine were more abundant in hVISA. Finally, we observed altered metabolic pathways in hVISA, including purine and pyrimidine pathway, CoA biosynthesis, amino acid metabolism and aminoacyl tRNA biosynthesis. Conclusions: Our results show that the mechanism of hVISA involves major changes in regulatory systems, expression of virulence factors and reduction in glycolysis via TCA cycle. This work contributes to the understanding of the development of this complex resistance mechanism in regional strains.
dc.description.versionVersión publicada
dc.identifier.citationBetsy E Castro and others, Multiomics characterization of methicillin-resistant Staphylococcus aureus (MRSA) isolates with heterogeneous intermediate resistance to vancomycin (hVISA) in Latin America, Journal of Antimicrobial Chemotherapy, Volume 78, Issue 1, January 2023, Pages 122–132, https://doi.org/10.1093/jac/dkac363
dc.identifier.doihttps://doi.org/10.1093/jac/dkac363
dc.identifier.urihttps://repositorio.udd.cl/handle/11447/7691
dc.language.isoen
dc.subjectVancomycin Resistance
dc.subjectAnti-Bacterial Agents
dc.subjectStaphylococcus aureus
dc.titleMultiomics characterization of methicillin-resistant Staphylococcus aureus (MRSA) isolates with heterogeneous intermediate resistance to vancomycin (hVISA) in Latin America
dc.typeArticle
dcterms.accessRightsAcceso abierto
dcterms.sourceJournal of antimicrobial Chemotherapy
dspace.entity.typePublication

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