Cell Wall Biosynthesis Genes Variability in Methicillin-Resistant Staphylococcus Aureus with Reduced Vancomycin Susceptibility

The problem of formation and spread of S.aureus isolates with reduced sensitivity to vancomycin (Vancomycin intermediate S.aureus, VISA) limits the use of this antibiotic for the treatment of infections caused by MRSA. The formation of such a phenotype is complex and is associated with the accumulat...

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Main Authors: V. V. Gostev, O. S. Kalinogorskaya, O. A. Dmitrenko, S'. M. Yudin, A. V. Kudryavtseva, S. V. Sydorenko
Format: Article
Language:Russian
Published: LLC "Publishing House OKI" 2020-05-01
Series:Антибиотики и Химиотерапия
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Online Access:https://www.antibiotics-chemotherapy.ru/jour/article/view/90
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author V. V. Gostev
O. S. Kalinogorskaya
O. A. Dmitrenko
S'. M. Yudin
A. V. Kudryavtseva
S. V. Sydorenko
author_facet V. V. Gostev
O. S. Kalinogorskaya
O. A. Dmitrenko
S'. M. Yudin
A. V. Kudryavtseva
S. V. Sydorenko
author_sort V. V. Gostev
collection DOAJ
description The problem of formation and spread of S.aureus isolates with reduced sensitivity to vancomycin (Vancomycin intermediate S.aureus, VISA) limits the use of this antibiotic for the treatment of infections caused by MRSA. The formation of such a phenotype is complex and is associated with the accumulation of mutations in the genes involved in the biosynthesis of the cell wall. Genomic sequencing of seven isolates with different sensitivity to vancomycin and belonging to the same genetic line was carried out in the study: ST8 - t008 - SCCmec IVc. PAP analysis of isolates with reduced sensitivity to vancomycin did not reveal hVISA/VISA phenotypes, while PAP/AUC was 0.53-0.7. Comparison of 83% of the core parts of isolates’ genomes with MIC = 1 mg/ml and 2 mg/ml, as well as control genomes (NCBI GenBank) with known sensitivity, revealed different clustering, the isolates with MIC=2 mg/ml were localized in one cluster. Comparison of the nucleotide concatenate composed of 44 genes involved in the assembly of the cell wall also showed that the isolates were assembled into one cluster. Unique mutations were identified for isolates with MIC=2 mg/ml in murZ (T353A), rpoB (Y946C), and fdh2 (G446S). Thus, isolates with reduced sensitivity to vancomycin did not have the hVISA or VISA phenotype. However, the identified mutations in the «key» genes of peptidoglycan biosynthesis may indicate the initial stage of selection of resistance to vancomycin with the formation of pre-hVISA.
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series Антибиотики и Химиотерапия
spelling doaj-art-0a5ebfffb322482d8ae56576edf85e332025-08-20T03:42:02ZrusLLC "Publishing House OKI"Антибиотики и Химиотерапия0235-29902020-05-01637-8111689Cell Wall Biosynthesis Genes Variability in Methicillin-Resistant Staphylococcus Aureus with Reduced Vancomycin SusceptibilityV. V. Gostev0O. S. Kalinogorskaya1O. A. Dmitrenko2S'. M. Yudin3A. V. Kudryavtseva4S. V. Sydorenko5Pediatric Research and Clinical Center for Infectious Diseases; North-West State Medical University named after I. I. MechnikovPediatric Research and Clinical Center for Infectious DiseasesCenter for Strategic Planning and Management of Biomedical Health RisksN. F. Gamaleya Federal Research Center for Epidemiology & MicrobiologyEngelhardt Institute of Molecular BiologyPediatric Research and Clinical Center for Infectious Diseases; North-West State Medical University named after I. I. MechnikovThe problem of formation and spread of S.aureus isolates with reduced sensitivity to vancomycin (Vancomycin intermediate S.aureus, VISA) limits the use of this antibiotic for the treatment of infections caused by MRSA. The formation of such a phenotype is complex and is associated with the accumulation of mutations in the genes involved in the biosynthesis of the cell wall. Genomic sequencing of seven isolates with different sensitivity to vancomycin and belonging to the same genetic line was carried out in the study: ST8 - t008 - SCCmec IVc. PAP analysis of isolates with reduced sensitivity to vancomycin did not reveal hVISA/VISA phenotypes, while PAP/AUC was 0.53-0.7. Comparison of 83% of the core parts of isolates’ genomes with MIC = 1 mg/ml and 2 mg/ml, as well as control genomes (NCBI GenBank) with known sensitivity, revealed different clustering, the isolates with MIC=2 mg/ml were localized in one cluster. Comparison of the nucleotide concatenate composed of 44 genes involved in the assembly of the cell wall also showed that the isolates were assembled into one cluster. Unique mutations were identified for isolates with MIC=2 mg/ml in murZ (T353A), rpoB (Y946C), and fdh2 (G446S). Thus, isolates with reduced sensitivity to vancomycin did not have the hVISA or VISA phenotype. However, the identified mutations in the «key» genes of peptidoglycan biosynthesis may indicate the initial stage of selection of resistance to vancomycin with the formation of pre-hVISA.https://www.antibiotics-chemotherapy.ru/jour/article/view/90mrsavisahvisamrsavancomycinvisahvisagenomic sequencingcell wall
spellingShingle V. V. Gostev
O. S. Kalinogorskaya
O. A. Dmitrenko
S'. M. Yudin
A. V. Kudryavtseva
S. V. Sydorenko
Cell Wall Biosynthesis Genes Variability in Methicillin-Resistant Staphylococcus Aureus with Reduced Vancomycin Susceptibility
Антибиотики и Химиотерапия
mrsa
visa
hvisa
mrsa
vancomycin
visa
hvisa
genomic sequencing
cell wall
title Cell Wall Biosynthesis Genes Variability in Methicillin-Resistant Staphylococcus Aureus with Reduced Vancomycin Susceptibility
title_full Cell Wall Biosynthesis Genes Variability in Methicillin-Resistant Staphylococcus Aureus with Reduced Vancomycin Susceptibility
title_fullStr Cell Wall Biosynthesis Genes Variability in Methicillin-Resistant Staphylococcus Aureus with Reduced Vancomycin Susceptibility
title_full_unstemmed Cell Wall Biosynthesis Genes Variability in Methicillin-Resistant Staphylococcus Aureus with Reduced Vancomycin Susceptibility
title_short Cell Wall Biosynthesis Genes Variability in Methicillin-Resistant Staphylococcus Aureus with Reduced Vancomycin Susceptibility
title_sort cell wall biosynthesis genes variability in methicillin resistant staphylococcus aureus with reduced vancomycin susceptibility
topic mrsa
visa
hvisa
mrsa
vancomycin
visa
hvisa
genomic sequencing
cell wall
url https://www.antibiotics-chemotherapy.ru/jour/article/view/90
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AT oadmitrenko cellwallbiosynthesisgenesvariabilityinmethicillinresistantstaphylococcusaureuswithreducedvancomycinsusceptibility
AT smyudin cellwallbiosynthesisgenesvariabilityinmethicillinresistantstaphylococcusaureuswithreducedvancomycinsusceptibility
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