Portal de investigación
Multiomics characterization of methicillin-resistant Staphylococcus aureus (MRSA) isolates with heterogeneous intermediate resistance to vancomycin (hVISA) in Latin America
Autores organización
Autores
- Rios R
- Vargas ML
- Cala MP
- León L
- Hanson B
- Dinh AQ
- Ortega-Recalde O
- Seas C
- Munita JM
- Arias CA
- Diaz L
Grupos de investigación
Resumen
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. © 2022 The Author(s). Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved.
© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Datos de la publicación
- ISSN/ISSNe:
- 0305-7453, 1460-2091
- Tipo:
- Article
- Páginas:
- 122-132
- DOI:
- 10.1093/jac/dkac363
- Enlace a otro recurso:
- www.scopus.com
Journal Of Antimicrobial Chemotherapy Oxford University Press
Citas Recibidas en Web of Science: 4
Citas Recibidas en Scopus: 7
Documentos
- No hay documentos
Filiaciones
Keywords
- Anti-Bacterial Agents; Bayes Theorem; Genome-Wide Association Study; Humans; Latin America; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Multiomics; Phylogeny; RNA, Transfer; Staphylococcal Infections; Staphylococcus aureus; Vancomycin; Vancomycin Resistance; Vancomycin-Resistant Staphylococcus aureus; amino acid; aminoacyl transfer RNA; arginine; autolysin; betaine; carbohydrate; coenzyme A; flavine adenine nucleotide; glycine; histidine; leucine; purine; pyrimidine; reduced nicotinamide adenine dinucleotide; threonine; transcriptome; transfer RNA; tyrosine; valine; vancomycin; virulence factor; antiinfective agent; transfer RNA; vancomycin; amino acid metabolism; amino acid substitution; Article; bacterial cell wall; bacterial gene; bacterial genome; bacterial metabolism; bacterial strain; bacterium adherence; bacterium isolate; Bayes theorem; biofilm; biosynthesis; capABCDE gene; carbohydrate metabolism; citric acid cycle; controlled study; core genome;
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Citar la publicación
Castro BE,Rios R,Carvajal LP,Vargas ML,Cala MP,León L,Hanson B,Dinh AQ,Ortega O,Seas C,Munita JM,Arias CA,Rincon S,Reyes J,Diaz L. Multiomics characterization of methicillin-resistant Staphylococcus aureus (MRSA) isolates with heterogeneous intermediate resistance to vancomycin (hVISA) in Latin America. J Antimicrob Chemother. 2023. 78. (1):p. 122-132. IF:3,900. (1).