scholarly journals Contribution of vraSR and graSR Point Mutations to Vancomycin Resistance in Vancomycin-Intermediate Staphylococcus aureus

2009 ◽  
Vol 53 (3) ◽  
pp. 1231-1234 ◽  
Author(s):  
Longzhu Cui ◽  
Hui-min Neoh ◽  
Mitsutaka Shoji ◽  
Keiichi Hiramatsu
Keyword(s):  
Staphylococcus Aureus ◽  
Genetic Analysis ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Genome Engineering ◽  
Point Mutations ◽  
Vancomycin Resistance ◽  
Whole Genome ◽  
Stepwise Evolution

ABSTRACT We describe here the genetic analysis of a vancomycin-susceptible Staphylococcus aureus (VSSA) strain, Mu50Ω, a strain related to vancomycin-intermediate S. aureus (VISA) strain Mu50. Using a combination of Mu50Ω whole-genome sequencing and genome engineering, we observed a stepwise evolution of vancomycin resistance from VSSA to VISA after the mutated vraS and graR genes of Mu50 were engineered into Mu50Ω.

scholarly journals Whole Genome Sequencing and Complete Genetic Analysis Reveals Novel Pathways to Glycopeptide Resistance in Staphylococcus aureus

PLoS ONE ◽  
2011 ◽  
Vol 6 (6) ◽  
pp. e21577 ◽  
Author(s):  
Adriana Renzoni ◽  
Diego O. Andrey ◽  
Ambre Jousselin ◽  
Christine Barras ◽  
Antoinette Monod ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Genetic Analysis ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Whole Genome ◽  
Glycopeptide Resistance

scholarly journals Mutated Response Regulator graR Is Responsible for Phenotypic Conversion of Staphylococcus aureus from Heterogeneous Vancomycin-Intermediate Resistance to Vancomycin-Intermediate Resistance

2007 ◽  
Vol 52 (1) ◽  
pp. 45-53 ◽  
Author(s):  
Hui-min Neoh ◽  
Longzhu Cui ◽  
Harumi Yuzawa ◽  
Fumihiko Takeuchi ◽  
Miki Matsuo ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Response Regulator ◽  
Regulatory System ◽  
Vancomycin Resistance ◽  
Whole Genome ◽  
Two Component ◽  
Intermediate Resistance ◽  
Mrsa Strains

ABSTRACT Multistep genetic alteration is required for methicillin-resistant Staphylococcus aureus (MRSA) to achieve the level of vancomycin resistance of vancomycin-intermediate S. aureus (VISA). In the progression of vancomycin resistance, strains with heterogeneous vancomycin resistance, designated hetero-VISA, are observed. In studying the whole-genome sequencing of the representative hetero-VISA strain Mu3 and comparing it with that of closely related MRSA strains Mu50 (VISA) and N315 (vancomycin-susceptible S. aureus [VSSA]), we identified a mutation in the response regulator of the graSR two-component regulatory system. Introduction of mutated graR, designated graR*, but not intact graR, designated graRn, could convert the hetero-VISA phenotype of Mu3 into a VISA phenotype which was comparable to that of Mu50. The same procedure did not appreciably increase the vancomycin resistance of VSSA strain N315, indicating that graR* expression was effective only in the physiological milieu of hetero-VISA cell to achieve a VISA phenotype. Interestingly, the overexpression of graR* increased the daptomycin MICs in both Mu3 and N315 and decreased the oxacillin MIC in N315.

scholarly journals Integrative Analysis of Whole Genome Sequencing and Phenotypic Resistance Toward Prediction of Trimethoprim-Sulfamethoxazole Resistance in Staphylococcus aureus

2021 ◽  
Vol 11 ◽  
Author(s):  
Dennis Nurjadi ◽  
Elfi Zizmann ◽  
Quan Chanthalangsy ◽  
Klaus Heeg ◽  
Sébastien Boutin
Keyword(s):  
Staphylococcus Aureus ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Point Mutations ◽  
Genetic Lineage ◽  
Whole Genome ◽  
Single Mutation ◽  
Protein Sequence Analysis ◽  
Sequencing Data ◽  
Phenotypic Resistance

As whole genome sequencing is becoming more accessible and affordable for clinical microbiological diagnostics, the reliability of genotypic antimicrobial resistance (AMR) prediction from sequencing data is an important issue to address. Computational AMR prediction can be performed at multiple levels. The first-level approach, such as simple AMR search relies heavily on the quality of the information fed into the database. However, AMR due to mutations are often undetected, since this is not included in the database or poorly documented. Using co-trimoxazole (trimethoprim-sulfamethoxazole) resistance in Staphylococcus aureus, we compared single-level and multi-level analysis to investigate the strengths and weaknesses of both approaches. The results revealed that a single mutation in the AMR gene on the nucleotide level may produce false positive results, which could have been detected if protein sequence analysis would have been performed. For AMR predictions based on chromosomal mutations, such as the folP gene of S. aureus, natural genetic variations should be taken into account to differentiate between variants linked to genetic lineage (MLST) and not over-estimate the potential resistant variants. Our study showed that careful analysis of the whole genome data and additional criterion such as lineage-independent mutations may be useful for identification of mutations leading to phenotypic resistance. Furthermore, the creation of reliable database for point mutations is needed to fully automatized AMR prediction.

scholarly journals Whole Genome Sequencing and Antimicrobial Resistance of Staphylococcus aureus from Surgical Site Infections in Ghana

Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 196
Author(s):  
Beverly Egyir ◽  
Jeannette Bentum ◽  
Naiki Attram ◽  
Anne Fox ◽  
Noah Obeng-Nkrumah ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Meca Gene ◽  
Surgical Site Infections ◽  
Illumina Miseq ◽  
Multi Drug Resistance ◽  
Toxin Gene ◽  
Whole Genome ◽  
Flight Mass Spectrometry

Staphylococcus aureus (S. aureus) is a common cause of surgical site infections (SSIs) globally. Data on the occurrence of methicillin-susceptible S. aureus (MSSA) as well as methicillin-resistant S. aureus (MRSA) among patients with surgical site infections (SSIs) in sub-Saharan African are scarce. We characterized S. aureus from SSIs in Ghana using molecular methods and antimicrobial susceptibility testing (AST). Wound swabs or aspirate samples were collected from subjects with SSIs. S. aureus was identified by matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF-MS); AST was performed by Kirby-Bauer disk diffusion, and results were interpreted according to the Clinical and Laboratory Standards Institute (CLSI) guideline. Detection of spa, mecA, and pvl genes was performed by polymerase chain reaction (PCR). Whole-genome sequencing (WGS) was done using the Illumina MiSeq platform. Samples were collected from 112 subjects, with 13 S. aureus isolates recovered. Of these, 92% were sensitive to co-trimoxazole, 77% to clindamycin, and 54% to erythromycin. Multi-drug resistance was detected in 5 (38%) isolates. The four mecA gene-positive MRSA isolates detected belonged to ST152 (n = 3) and ST5 (n = 1). In total, 62% of the isolates were positive for the Panton-Valentine leukocidin (pvl) toxin gene. This study reports, for the first time, a pvl-positive ST152-t355 MRSA clone from SSIs in Ghana. The occurrence of multi-drug-resistant S. aureus epidemic clones suggests that continuous surveillance is required to monitor the spread and resistance trends of S. aureus in hospital settings in the country.

Divergent variant patterns among 19 patients with Rubinstein‐Taybi syndrome uncovered by comprehensive genetic analysis including whole genome sequencing

2021 ◽  
Author(s):  
Yumi Enomoto ◽  
Takayuki Yokoi ◽  
Yoshinori Tsurusaki ◽  
Hiroaki Murakami ◽  
Makiko Tominaga ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Whole Genome
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