scholarly journals Identification of a novel tedizolid resistance mutation in rpoB of methicillin-resistant Staphylococcus aureus

2019 ◽  
Author(s):  
Tianwei Shen ◽  
Kelsi Penewit ◽  
Adam Waalkes ◽  
Libin Xu ◽  
Stephen J. Salipante ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Resistance Mutation ◽  
Serial Passage ◽  
Resistant Isolate ◽  
Cross Resistance ◽  
Whole Genome ◽  
Single Nucleotide ◽  
First Time ◽  
Ribosomal Complex

AbstractA tedizolid-resistant isolate of MRSA was selected by serial passage. Whole genome sequencing revealed only a single nucleotide variant in rpoB. Cross-resistance to linezolid, chloramphenicol, and quinupristin-dalfopristin was observed but susceptibility to other drugs including rifampin was unchanged. Models of the RNA-polymerase-ribosomal complex revealed that the mutated residue was unlikely to interact directly with the oxazolidinone binding site. This is the first time that rpoB mutation has been associated with resistance to the PhLOPSa antimicrobials.

scholarly journals Whole-Genome Sequence for Methicillin-Resistant Staphylococcus aureus Strain ATCC BAA-1680

2015 ◽  
Vol 3 (2) ◽  
Author(s):  
Luke T. Daum ◽  
Violet V. Bumah ◽  
Daniela S. Masson-Meyers ◽  
Manjeet Khubbar ◽  
John D. Rodriguez ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Genome Sequence ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Whole Genome Sequence ◽  
Aureus Strain ◽  
Whole Genome ◽  
Strain Atcc ◽  
Methicillin Resistant

scholarly journals Current Status of Staphylococcal Cassette Chromosome mec (SCCmec)

Antibiotics ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 86
Author(s):  
Yuki Uehara
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Sccmec Type ◽  
Current Status ◽  
Whole Genome ◽  
Identification Methods ◽  
Sccmec Types ◽  
Staphylococcal Cassette Chromosome ◽  
Conventional Sequencing

Staphylococcal cassette chromosome mec (SCCmec) typing was established in the 2000s and has been employed as a tool for the molecular epidemiology of methicillin-resistant Staphylococcus aureus, as well as the evolution investigation of Staphylococcus species. Molecular cloning and the conventional sequencing of SCCmec have been adopted to verify the presence and structure of a novel SCCmec type, while convenient PCR-based SCCmec identification methods have been used in practical settings for many years. In addition, whole-genome sequencing has been widely used, and various SCCmec and similar structures have been recently identified in various species. The current status of the SCCmec types, SCCmec subtypes, rules for nomenclature, and multiple methods for identifying SCCmec types and subtypes were summarized in this review, according to the perspective of the International Working Group on the Classification of Staphylococcal Cassette Chromosome Elements.

scholarly journals Identification of a novel tedizolid resistance mutation in rpoB of MRSA after in vitro serial passage

2020 ◽  
Author(s):  
Tianwei Shen ◽  
Kelsi Penewit ◽  
Adam Waalkes ◽  
Libin Xu ◽  
Stephen J Salipante ◽  
...  
Keyword(s):  
Protein Function ◽  
Homology Modelling ◽  
Resistance Mutation ◽  
Laboratory Strain ◽  
Serial Passage ◽  
Cross Resistance ◽  
Σ Factor ◽  
Rpob Mutation ◽  
Stable Mutant

Abstract Objectives Tedizolid is an oxazolidinone antimicrobial with activity against Gram-positive bacteria, including MRSA. Tedizolid resistance is uncommon and tedizolid’s capacity to select for cross-resistance to other antimicrobials is incompletely understood. The objective of this study was to further explore the phenotypic and genetic basis of tedizolid resistance in MRSA. Methods We selected for tedizolid resistance in an MRSA laboratory strain, N315, by serial passage until an isolate with an MIC ≥1 log2 dilution above the breakpoint for resistance (≥2 mg/L) was recovered. This isolate was subjected to WGS and susceptibility to a panel of related and unrelated antimicrobials was tested in order to determine cross-resistance. Homology modelling was performed to evaluate the potential impact of the mutation on target protein function. Results After 10 days of serial passage we recovered a phenotypically stable mutant with a tedizolid MIC of 4 mg/L. WGS revealed only one single nucleotide variant (A1345G) in rpoB, corresponding to amino acid substitution D449N. MICs of linezolid, chloramphenicol, retapamulin and quinupristin/dalfopristin increased by ≥2 log2 dilutions, suggesting the emergence of the so-called ‘PhLOPSa’ resistance phenotype. Susceptibility to other drugs, including rifampicin, was largely unchanged. Homology models revealed that the mutated residue of RNA polymerase would be unlikely to directly affect oxazolidinone action. Conclusions To the best of our knowledge, this is the first time that an rpoB mutation has been implicated in resistance to PhLOPSa antimicrobials. The mechanism of resistance remains unclear, but is likely indirect, involving σ-factor binding or other alterations in transcriptional regulation.

scholarly journals Formyl-Peptide Receptor Activation Enhances Phagocytosis of Community-Acquired Methicillin-Resistant Staphylococcus aureus

2019 ◽  
Author(s):  
Elisabeth Weiß ◽  
Katja Schlatterer ◽  
Christian Beck ◽  
Andreas Peschel ◽  
Dorothee Kretschmer
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Receptor Activation ◽  
Formyl Peptide Receptor ◽  
Peptide Receptors ◽  
Highly Pathogenic ◽  
Methicillin Resistant ◽  
Formyl Peptide Receptors ◽  
Formyl Peptide ◽  
First Time

Abstract Background Formyl-peptide receptors (FPRs) are important pattern recognition receptors that sense specific bacterial peptides. Formyl-peptide receptors are highly expressed on neutrophils and monocytes, and their activation promotes the migration of phagocytes to sites of infection. It is currently unknown whether FPRs may also influence subsequent processes such as bacterial phagocytosis and killing. Staphylococcus aureus, especially highly pathogenic community-acquired methicillin-resistant S aureus strains, release high amounts of FPR2 ligands, the phenol-soluble modulins. Methods We demonstrate that FPR activation leads to upregulation of complement receptors 1 and 3 as well as FCγ receptor I on neutrophils and, consequently, increased opsonic phagocytosis of S aureus and other pathogens. Results Increased phagocytosis promotes killing of S aureus and interleukin-8 release by neutrophils. Conclusions We show here for the first time that FPRs govern opsonic phagocytosis. Manipulation of FPR2 activation could open new therapeutic opportunities against bacterial pathogens.

scholarly journals Carriage Methicillin-Resistant Staphylococcus aureus in Poultry and Cattle in Northern Algeria

2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Saliha Bounar-Kechih ◽  
Mossadak Taha Hamdi ◽  
Hebib Aggad ◽  
Nacima Meguenni ◽  
Zafer Cantekin
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Resistance ◽  
Broiler Chickens ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Laying Hens ◽  
Methicillin Resistance ◽  
Public Health Problem ◽  
Cross Resistance ◽  
Isolation And Identification ◽  
Methicillin Resistant

Multiresistant and especially Methicillin-Resistant Staphylococcus aureus (MRSA) poses a serious public health problem that requires their immediate identification and antibiotic resistance characteristics. In order to determine antibiotic resistance S. aureus poultry and bovine origin, 8840 samples were collected from slaughterhouses in the northern region of Algeria between years 2009 and 2014. 8375 samples were from an avian origin (1875 from laying hens and 6500 from broiler chickens) and the rest was from bovine origin. Bacteriological isolation and identification were made by classical culture method and antibiotic resistance patterns were determined by disc diffusion test. The prevalence of S. aureus was 42% in laying hens, 12% in broilers, and 55% in bovine samples. The prevalence of MRSA was 57%, 50%, and 31% in laying hens, broiler chickens, and bovine, respectively. While MRSA strains isolated from poultry showed cross-resistance to aminoglycosides, fluoroquinolones, macrolides, sulphonamides, and cyclins, those isolated from bovine also revealed similar multiresistance except for sulphonamide. This high percentage of methicillin resistance and multidrug resistance in S. aureus poultry and bovine origin may have importance for human health and curing of human infections.

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