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

Journal
Journal of Antimicrobial Chemotherapy
ISSN
0305-7453
Date Issued
2022
Author(s)
Betsy E Castro
Rafael Rios
Lina P Carvajal
Mónica L Vargas
Mónica P Cala
Lizeth León
Blake Hanson
An Q Dinh
Oscar Ortega-Recalde
Carlos Seas
Cesar A Arias
Sandra Rincon
Jinnethe Reyes
Type
Resource Types::text::journal::journal article
Scopus ID
2-s2.0-85144597523
WoS ID
WOS:000877750300001
DOI
URL
URL Institutional Repository
Abstract
<jats:title>Abstract</jats:title>
<jats:sec>
<jats:title>Background</jats:title>
<jats:p>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.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Objective</jats:title>
<jats:p>To characterize the biomolecular profile of clinical hVISA applying genomic, transcriptomic and metabolomic approaches.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Methods</jats:title>
<jats:p>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.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Results</jats:title>
<jats:p>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.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Conclusions</jats:title>
<jats:p>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.</jats:p>
</jats:sec>
Cite this document
Castro, B. E., Rios, R., Carvajal, L. P., Vargas, M. L., Cala, M. P., León, L., Hanson, B., Dinh, A. Q., Ortega-Recalde, O., Seas, C., Munita, J. M., Arias, C. A., Rincon, S., Reyes, J., & Diaz, L. (2023). Multiomics characterization of methicillin-resistant Staphylococcus aureus (Mrsa) isolates with heterogeneous intermediate resistance to vancomycin (Hvisa) in Latin America. Journal of Antimicrobial Chemotherapy, 78(1), 122-132. https://doi.org/10.1093/jac/dkac363
Project(s)
Subjects
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

; 

differential gene expression

; 

discriminant analysis

; 

down regulation

; 

esaa gene

; 

esad gene

; 

gene expression level

; 

gene overexpression

; 

genome-wide association study

; 

genomics

; 

glycolysis

; 

hydrophilicity

; 

lacabcdefg gene

; 

liquid chromatography

; 

metabolic fingerprinting

; 

metabolite

; 

metabolomics

; 

methicillin resistant staphylococcus aureus

; 

molecular biology

; 

multiomics

; 

nonhuman

; 

phenotype

; 

phylogeny

; 

protein expression level

; 

regulatory mechanism

; 

rna sequencing

; 

rna synthesis

; 

sdrd gene

; 

single nucleotide polymorphism

; 

south and central america

; 

ssaa gene

; 

transcriptomics

; 

vancomycin intermediate staphylococcus aureus

; 

vancomycin resistance

; 

vancomycin susceptible staphylococcus aureus

; 

genetics

; 

human

; 

microbial sensitivity test

; 

staphylococcus aureus

; 

staphylococcus infection

; 

vancomycin resistance