Academic Journal
Identification of genetic mutations conferring tedizolid resistance in MRSA mutants.
| Τίτλος: | Identification of genetic mutations conferring tedizolid resistance in MRSA mutants. |
|---|---|
| Συγγραφείς: | Goda NB; Microbiology and Immunology Department, Faculty of Pharmacy, Egyptian Russian University, Badr, Egypt. nesma-barbary@eru.edu.eg., El-Ganiny AM; Microbiology and Immunology Department, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt., El-Khamissy TR; Microbiology and Immunology Department, Faculty of Pharmacy, Egyptian Russian University, Badr, Egypt., Najar FZ; High-Performance Computing Center MS #105, Oklahoma State University, Stillwater, OK, 74078, USA., Kadry AA; Microbiology and Immunology Department, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt. |
| Πηγή: | European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology [Eur J Clin Microbiol Infect Dis] 2025 Aug; Vol. 44 (8), pp. 1917-1924. Date of Electronic Publication: 2025 May 13. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Springer Country of Publication: Germany NLM ID: 8804297 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1435-4373 (Electronic) Linking ISSN: 09349723 NLM ISO Abbreviation: Eur J Clin Microbiol Infect Dis Subsets: MEDLINE |
| Imprint Name(s): | Publication: Berlin : Springer Original Publication: [Wiesbaden, Federal Republic of Germany] : Vieweg, [c1988- |
| Ιατρικοί όροι (MeSH): | Anti-Bacterial Agents*/pharmacology , Methicillin-Resistant Staphylococcus aureus*/genetics , Methicillin-Resistant Staphylococcus aureus*/drug effects , Methicillin-Resistant Staphylococcus aureus*/isolation & purification , Oxazolidinones*/pharmacology , Drug Resistance, Bacterial*/genetics , Mutation*, Bacterial Proteins/genetics ; Linezolid/pharmacology ; Staphylococcal Infections/microbiology ; Humans ; Microbial Sensitivity Tests ; Whole Genome Sequencing ; Ribosomal Protein L3 ; Tetrazoles |
| Περίληψη: | Purpose: In light of previous studies eliminating the involvement of gene-mediated mechanisms in developing tedizolid resistance, our study elucidates the ability of mutation-mediated mechanisms to confer oxazolidinones cross-resistance in methicillin-resistant Staphylococcus aureus (MRSA). With further investigation of the identified mutations and their relation to tedizolid resistance. Additionally, the involvement of rpoB mutations in acquiring resistance to tedizolid was also investigated. Methods: Five cfr-negative, methicillin-resistant Staphylococcus aureus clinical isolates were subjected to in vitro selection to develop linezolid-resistant mutants. The resultant mutants were tested for acquiring tedizolid cross-resistance, whole genome sequencing was performed twice, followed by variant calling and annotation. Detected mutations were analyzed for their relatedness to the developed resistance. Results: Mutations considered relevant to tedizolid resistance were detected in rpoB gene encoding β-subunit of the RNA polymerase enzyme and rplC gene encoding the 50S ribosomal protein L3. Additionally, mutations in mepB gene, part of the mepRAB operon were detected and believed to contribute to acquiring linezolid resistance. Conclusion: To the best of our knowledge, our findings are the first to report the 50S ribosomal protein L3 mutation Gly152Asp to solely confer cross-resistance to both linezolid and tedizolid oxazolidinones. In addition, we report the emergence of cross-resistance between oxazolidinone antibiotics and rifampin through a single amino-acid substitution occurring within the Rifampin Resistance Determining Region (RRDR). Furthermore, mepB mutations reported in our results support a theory implying a second MepR-independent mechanism regulating the mepRAB operon, and are believed to be responsible for the acquired linezolid resistance in our study. (© 2025. The Author(s).) |
| Competing Interests: | Declarations. Ethical approval: Not applicable. Informed consent: Not applicable. Competing interests: The authors declare no competing interests. |
| References: | Nucleic Acids Res. 2014 Feb;42(4):2774-88. (PMID: 24293644) Antimicrob Agents Chemother. 1999 Nov;43(11):2813-6. (PMID: 10543773) Int J Mol Sci. 2012;13(4):4484-4495. (PMID: 22605991) J Infect Public Health. 2018 Sep - Oct;11(5):605-610. (PMID: 29706316) Antimicrob Agents Chemother. 2010 Dec;54(12):5337-43. (PMID: 20837751) Lancet. 1993 Mar 13;341(8846):647-50. (PMID: 8095569) Antimicrob Agents Chemother. 2015 Oct;59(10):6262-5. (PMID: 26248355) Antimicrob Agents Chemother. 2009 Dec;53(12):5265-74. (PMID: 19752277) J Antimicrob Chemother. 2016 Jan;71(1):152-5. (PMID: 26476277) J Clin Microbiol. 2005 Oct;43(10):5026-33. (PMID: 16207957) Ann Clin Microbiol Antimicrob. 2022 Aug 17;21(1):37. (PMID: 35978400) Antimicrob Agents Chemother. 2005 May;49(5):1857-64. (PMID: 15855507) Antimicrob Agents Chemother. 2006 Apr;50(4):1276-81. (PMID: 16569840) BMC Microbiol. 2010 Mar 04;10:68. (PMID: 20202188) Molecules. 2021 Jul 14;26(14):. (PMID: 34299555) Protein Sci. 2014 May;23(5):594-602. (PMID: 24501097) J Antimicrob Chemother. 2021 Jan 19;76(2):292-296. (PMID: 33057715) Infect Drug Resist. 2021 Oct 05;14:4119-4128. (PMID: 34675557) Lancet. 2001 Jul 21;358(9277):207-8. (PMID: 11476839) PLoS One. 2015 Nov 24;10(11):e0143670. (PMID: 26599635) Microb Drug Resist. 2021 Feb;27(2):145-153. (PMID: 32456543) RNA Biol. 2004 May;1(1):59-65. (PMID: 17194937) Tuber Lung Dis. 1998;79(1):3-29. (PMID: 10645439) J Clin Microbiol. 2016 May;54(5):1289-94. (PMID: 26935728) Antimicrob Agents Chemother. 2006 Apr;50(4):1156-63. (PMID: 16569824) Med Sci Monit. 2011 Feb;17(2):BR48-53. (PMID: 21278685) J Bacteriol. 2013 Aug;195(16):3651-62. (PMID: 23749979) J Glob Antimicrob Resist. 2020 Sep;22:631-636. (PMID: 32590185) J Clin Microbiol. 2021 Mar 19;59(4):. (PMID: 32999007) BMC Microbiol. 2012 Oct 22;12:240. (PMID: 23082766) J Antimicrob Chemother. 2003 Jan;51(1):186-8. (PMID: 12493812) Antimicrob Agents Chemother. 2006 Jul;50(7):2500-5. (PMID: 16801432) J Bacteriol. 2013 Feb;195(3):523-33. (PMID: 23175649) Antimicrob Agents Chemother. 1996 Apr;40(4):1053-6. (PMID: 8849230) Antimicrob Agents Chemother. 2012 Feb;56(2):603-12. (PMID: 22143525) Antimicrob Agents Chemother. 2011 Apr;55(4):1684-92. (PMID: 21263048) |
| Contributed Indexing: | Keywords: mepB; mepRAB operon; Cross-resistance; MRSA; Mutation; Tedizolid |
| Substance Nomenclature: | 0 (Anti-Bacterial Agents) 0 (Bacterial Proteins) 0 (Oxazolidinones) 97HLQ82NGL (tedizolid) ISQ9I6J12J (Linezolid) 0 (Ribosomal Protein L3) 0 (Tetrazoles) |
| Entry Date(s): | Date Created: 20250513 Date Completed: 20250805 Latest Revision: 20260127 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC12321651 |
| DOI: | 10.1007/s10096-025-05157-x |
| PMID: | 40360924 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1435-4373 |
|---|---|
| DOI: | 10.1007/s10096-025-05157-x |