Nueva Publicación de nuestro investigador Carlos Seas en Journal of Antimicrobial Chemotherapy. 

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

Betsy E Castro 1Rafael Rios 1Lina P Carvajal 1Mónica L Vargas 1Mónica P Cala 2Lizeth León 2Blake Hanson 3An Q Dinh 3 4 5Oscar Ortega-Recalde 5Carlos Seas 6Jose M Munita 7 8Cesar A Arias 4 9Sandra Rincon 1Jinnethe Reyes 1Lorena Diaz 1 7 8

Affiliations

  1. Molecular Genetics and Antimicrobial Resistance Unit, Universidad El Bosque, Bogota, Colombia.
  2. Metabolomics Core Facility-MetCore, Vice-Presidency for Research, Universidad de los Andes, Bogotá, Colombia.
  3. Center for Infectious Diseases, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA.
  4. Division of Infectious Diseases, Houston Methodist Hospital, Houston, TX, USA.
  5. Center for Research in Genetics and Genomics-CIGGUR, GENIUROS Research Group, School of Medicine and Health Sciences, Universidad Del Rosario, Bogotá, Colombia.
  6. Instituto de Medicina Tropical Alexander Von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru.
  7. Millennium Initiative for Collaborative Research on Bacterial Resistance (MICROB-R), Santiago, Chile.
  8. Genomics and Resistant Microbes (GeRM) Group. Clínica Alemana de Santiago, Universidad del Desarrollo School of Medicine, Santiago, Chile.
  9. Center for Infectious Diseases, Houston Methodist Research Institute, Houston, TX, USA.

 PMID: 36322484       DOI: 10.1093/jac/dkac363

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.

© 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: Esta dirección de correo electrónico está siendo protegida contra los robots de spam. Necesita tener JavaScript habilitado para poder verlo..

 

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