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Published on: March 14, 2019
Novel single-nucleotide variations associated with vancomycin resistance in vancomycin-intermediate Staphylococcus
Lee-Chung Lin1, Shih-Cheng Chang1,2, Mao-Cheng Ge1
1Department of Laboratory Medicine, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.
Abstract:
Prolonged vancomycin usage may cause methicillin-resistant Staphylococcus aureus to become vancomycin-intermediate S. aureus (VISA) and heterogeneous VISA (hVISA). Mechanisms of vancomycin resistance of VISA and hVISA are still unclear. In this study, analyses of nucleotide sequence variations in 30 vancomycin-sensitive S. aureus (VSSA), 41 hVISA and 16 VISA isolates revealed 29 single-nucleotide variations in 12 genes (fmtC, graR, graS, htrA, mecA, pbp2, pbp4, srtA, tcaA, upps, vicK and vraR) that are related to cell wall synthesis or the two-component system. Six of these 29 single-nucleotide variations were novel and resulted in the following amino acid changes: Q692E in FmtC; T278I, P306L and I311T in HtrA; and I63V and K101E in Upps. Since P306L and I311T in HtrA and I63V in Upps were present in the majority (76.7%-86.7%) of VSSA isolates, these three amino acid variations may not be associated with vancomycin resistance. The other three amino acid variations (T278I in HtrA, K101E in Upps and Q692E in FmtC) were present in the majority (87.5%-93.8%) of hVISA and VISA isolates, but only in a small number (22.9%-25.7%) of VSSA isolates, suggesting that they are associated with vancomycin resistance.
Insights
Prolonged vancomycin use can lead to vancomycin-intermediate Staphylococcus aureus (VISA). This study identified novel genetic variations in VISA and heterogeneous VISA strains, suggesting specific amino acid changes in FmtC, HtrA, and Upps are linked to vancomycin resistance.
Area of Science:
- Microbiology
- Genetics
- Molecular Biology
Background:
- Prolonged vancomycin treatment can induce resistance in Staphylococcus aureus, leading to vancomycin-intermediate (VISA) and heterogeneous (hVISA) strains.
- The precise genetic mechanisms underlying VISA and hVISA development remain incompletely understood.
Purpose of the Study:
- To investigate nucleotide sequence variations in genes associated with cell wall synthesis and two-component systems in vancomycin-sensitive (VSSA), hVISA, and VISA isolates.
- To identify potential genetic markers associated with vancomycin resistance in Staphylococcus aureus.
Main Methods:
- Analysis of nucleotide sequences from 30 VSSA, 41 hVISA, and 16 VISA isolates.
- Identification and comparison of single-nucleotide variations across 12 key genes.
Main Results:
- Twenty-nine single-nucleotide variations were identified in 12 genes.
- Six novel variations resulted in amino acid changes: Q692E in FmtC; T278I, P306L, I311T in HtrA; and I63V, K101E in Upps.
- Three specific amino acid variations (T278I in HtrA, K101E in Upps, Q692E in FmtC) were significantly more prevalent in hVISA and VISA isolates compared to VSSA isolates.
Conclusions:
- The study suggests that specific amino acid substitutions in FmtC, HtrA, and Upps are associated with the development of vancomycin resistance in Staphylococcus aureus.
- These findings contribute to understanding the genetic basis of VISA and hVISA, potentially aiding in the development of future diagnostic or therapeutic strategies.
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