http://purl.uniprot.org/citations/35736238 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/35736238 | http://www.w3.org/2000/01/rdf-schema#comment | "Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterial pathogen that presents great health concerns. Treatment requires the use of last-line antibiotics, such as members of the oxazolidinone family, of which linezolid is the first member to see regular use in the clinic. Here, we report a short time scale selection experiment in which strains of MRSA were subjected to linezolid treatment. Clonal isolates which had evolved a linezolid-resistant phenotype were characterized by whole-genome sequencing. Linezolid-resistant mutants were identified which had accumulated mutations in the ribosomal protein uL3. Multiple clones which had two mutations in uL3 exhibited resistance to linezolid, 2-fold higher than the clinical breakpoint. Ribosomes from this strain were isolated and subjected to single-particle cryo-electron microscopic analysis and compared to the ribosomes from the parent strain. We found that the mutations in uL3 lead to a rearrangement of a loop that makes contact with Helix 90, propagating a structural change over 15 Å away. This distal change swings nucleotide U2504 into the binding site of the antibiotic, causing linezolid resistance. IMPORTANCE Antibiotic resistance poses a critical problem to human health and decreases the utility of these lifesaving drugs. Of particular concern is the "superbug" methicillin-resistant Staphylococcus aureus (MRSA), for which treatment of infection requires the use of last-line antibiotics, including linezolid. In this paper, we characterize the atomic rearrangements which the ribosome, the target of linezolid, undergoes during its evolutionary journey toward becoming drug resistant. Using cryo-electron microscopy, we describe a particular molecular mechanism which MRSA uses to become resistant to linezolid."xsd:string |
http://purl.uniprot.org/citations/35736238 | http://purl.org/dc/terms/identifier | "doi:10.1128/spectrum.00583-22"xsd:string |
http://purl.uniprot.org/citations/35736238 | http://purl.uniprot.org/core/author | "Wright A."xsd:string |
http://purl.uniprot.org/citations/35736238 | http://purl.uniprot.org/core/author | "Bamert R.S."xsd:string |
http://purl.uniprot.org/citations/35736238 | http://purl.uniprot.org/core/author | "Belousoff M.J."xsd:string |
http://purl.uniprot.org/citations/35736238 | http://purl.uniprot.org/core/author | "Lithgow T."xsd:string |
http://purl.uniprot.org/citations/35736238 | http://purl.uniprot.org/core/author | "Johnson R.M."xsd:string |
http://purl.uniprot.org/citations/35736238 | http://purl.uniprot.org/core/author | "Tan K.S."xsd:string |
http://purl.uniprot.org/citations/35736238 | http://purl.uniprot.org/core/author | "Lupton D."xsd:string |
http://purl.uniprot.org/citations/35736238 | http://purl.uniprot.org/core/author | "Piper S.J."xsd:string |
http://purl.uniprot.org/citations/35736238 | http://purl.uniprot.org/core/author | "Stubenrauch C.J."xsd:string |
http://purl.uniprot.org/citations/35736238 | http://purl.uniprot.org/core/author | "Perlaza-Jimenez L."xsd:string |
http://purl.uniprot.org/citations/35736238 | http://purl.uniprot.org/core/date | "2022"xsd:gYear |
http://purl.uniprot.org/citations/35736238 | http://purl.uniprot.org/core/name | "Microbiol Spectr"xsd:string |
http://purl.uniprot.org/citations/35736238 | http://purl.uniprot.org/core/pages | "e0058322"xsd:string |
http://purl.uniprot.org/citations/35736238 | http://purl.uniprot.org/core/title | "A Structurally Characterized Staphylococcus aureus Evolutionary Escape Route from Treatment with the Antibiotic Linezolid."xsd:string |
http://purl.uniprot.org/citations/35736238 | http://purl.uniprot.org/core/volume | "10"xsd:string |
http://purl.uniprot.org/citations/35736238 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/35736238 |
http://purl.uniprot.org/citations/35736238 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/35736238 |
http://purl.uniprot.org/uniprot/#_P0A0F8-mappedCitation-35736238 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/35736238 |
http://purl.uniprot.org/uniprot/#_P0A0G2-mappedCitation-35736238 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/35736238 |
http://purl.uniprot.org/uniprot/#_Q2FJE0-mappedCitation-35736238 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/35736238 |
http://purl.uniprot.org/uniprot/#_Q2FUQ0-mappedCitation-35736238 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/35736238 |
http://purl.uniprot.org/uniprot/#_Q2FW06-mappedCitation-35736238 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/35736238 |