Identification and characterization of mutations responsible for the β-lactam resistance in oxacillin-susceptible mecA-positive Staphylococcus aureus
| Autor: | Feng-Yu Li, Longzhu Cui, Remi Takenouchi, Teppei Sasahara, Aa Haeruman Azam, Shinya Watanabe, Yusuke Taki, Xin-Ee Tan, Yuancheng Zhang, Tanit Boonsiri, Kotaro Kiga, Tomofumi Kawaguchi, Ryu Narimatsu, Kosuke Sasaki, Yoshifumi Aiba, Kanate Thitiananpakorn, Yusuke Sato’o |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Staphylococcus aureus Transcription Genetic Stringent response Operon 030106 microbiology Mutant lcsh:Medicine Down-Regulation Microbial Sensitivity Tests Biology medicine.disease_cause Microbiology Article beta-Lactam Resistance 03 medical and health sciences chemistry.chemical_compound Bacterial Proteins Transcription (biology) RNA polymerase medicine Genetics Humans lcsh:Science Gene Phylogeny Oxacillin Multidisciplinary Genome lcsh:R DNA-Directed RNA Polymerases Gene Expression Regulation Bacterial biochemical phenomena metabolism and nutrition Staphylococcal Infections Anti-Bacterial Agents Up-Regulation 030104 developmental biology chemistry Transfer RNA Mutation lcsh:Q Genome-Wide Association Study |
| Zdroj: | Scientific Reports Scientific Reports, Vol 10, Iss 1, Pp 1-22 (2020) |
| ISSN: | 2045-2322 |
| Popis: | Staphylococcus aureus strains that are susceptible to the β-lactam antibiotic oxacillin despite carrying mecA (OS-MRSA) cause serious clinical problems globally because of their ability to easily acquire β-lactam resistance. Understanding the genetic mechanism(s) of acquisition of the resistance is therefore crucial for infection control management. For this purpose, a whole-genome sequencing-based analysis was performed using 43 clinical OS-MRSA strains and 100 mutants with reduced susceptibility to oxacillin (MICs 1.0–256 µg/mL) generated from 26 representative OS-MRSA strains. Genome comparison between the mutants and their respective parent strains identified a total of 141 mutations in 46 genes and 8 intergenic regions. Among them, the mutations are frequently found in genes related to RNA polymerase (rpoBC), purine biosynthesis (guaA, prs, hprT), (p)ppGpp synthesis (relSau), glycolysis (pykA, fbaA, fruB), protein quality control (clpXP, ftsH), and tRNA synthase (lysS, gltX), whereas no mutations existed in mec and bla operons. Whole-genome transcriptional profile of the resistant mutants demonstrated that expression of genes associated with purine biosynthesis, protein quality control, and tRNA synthesis were significantly inhibited similar to the massive transcription downregulation seen in S. aureus during the stringent response, while the levels of mecA expression and PBP2a production were varied. We conclude that a combination effect of mecA upregulation and stringent-like response may play an important role in acquisition of β-lactam resistance in OS-MRSA. |
| Databáze: | OpenAIRE |
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