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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.author Castro, Betsy E.
dc.contributor.author Rios, Rafael
dc.contributor.author Carvajal, Lina P.
dc.contributor.author Vargas, Monica L.
dc.contributor.author Cala, Monica P.
dc.contributor.author Leon, Lizeth
dc.contributor.author Hanson, Blake
dc.contributor.author Dinh, An Q.
dc.contributor.author Ortega-Recalde, Oscar
dc.contributor.author Seas Ramos, Carlos Rafael
dc.contributor.author Munita, Jose M.
dc.contributor.author Arias, Cesar A.
dc.contributor.author Rincon, Sandra
dc.contributor.author Reyes, Jinnethe
dc.contributor.author Diaz, Lorena
dc.date.accessioned 2022-11-15T23:04:41Z
dc.date.available 2022-11-15T23:04:41Z
dc.date.issued 2022
dc.identifier.uri https://hdl.handle.net/20.500.12866/12592
dc.description.abstract BACKGROUND: 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. en_US
dc.language.iso eng
dc.publisher Oxford University Press
dc.relation.ispartofseries Journal of Antimicrobial Chemotherapy
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject methicillin-resistant Staphylococcus aureus (MRSA) en_US
dc.subject resistance en_US
dc.subject vancomycin (hVISA) en_US
dc.subject Latin America en_US
dc.title Multiomics characterization of methicillin-resistant Staphylococcus aureus (MRSA) isolates with heterogeneous intermediate resistance to vancomycin (hVISA) in Latin America. en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1093/jac/dkac363
dc.relation.issn 1460-2091


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