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In vivo development of elevated linezolid resistance mediated by a deletion in ribosomal protein L3 in clinical Enterococcus faecium.

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Τίτλος: In vivo development of elevated linezolid resistance mediated by a deletion in ribosomal protein L3 in clinical Enterococcus faecium.
Συγγραφείς: Sun L; Department of Laboratory Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.; Zhejiang Key Laboratory of Clinical In Vitro Diagnostic Techniques, Hangzhou, China.; Institute of Laboratory Medicine, Zhejiang University, Hangzhou, China., Lei T; Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.; Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province, Hangzhou, China.; Regional Medical Center for National Institute of Respiratory Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China., Liu Y; Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.; Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province, Hangzhou, China.; Regional Medical Center for National Institute of Respiratory Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China., Lu S; Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.; Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province, Hangzhou, China.; Regional Medical Center for National Institute of Respiratory Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China., Hua X; Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.; Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province, Hangzhou, China.; Regional Medical Center for National Institute of Respiratory Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China., Zhang J; Hangzhou Linping Traditional Chinese Medicine Hospital, Hangzhou, China., Chen Y; Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.; Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province, Hangzhou, China.; Regional Medical Center for National Institute of Respiratory Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Πηγή: Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2025 Dec 10; Vol. 69 (12), pp. e0087125. Date of Electronic Publication: 2025 Oct 28.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 0315061 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1098-6596 (Electronic) Linking ISSN: 00664804 NLM ISO Abbreviation: Antimicrob Agents Chemother Subsets: MEDLINE
Imprint Name(s): Original Publication: Washington, American Society for Microbiology
Ιατρικοί όροι (MeSH): Linezolid*/pharmacology , Linezolid*/therapeutic use , Enterococcus faecium*/drug effects , Enterococcus faecium*/genetics , Enterococcus faecium*/isolation & purification , Ribosomal Proteins*/genetics , Ribosomal Proteins*/metabolism , Anti-Bacterial Agents*/pharmacology , Drug Resistance, Bacterial*/genetics, Bacterial Proteins/genetics ; Gram-Positive Bacterial Infections/microbiology ; Gram-Positive Bacterial Infections/drug therapy ; Ribosomal Protein L3 ; Humans ; Microbial Sensitivity Tests
Περίληψη: Gram-positive bacteria can develop resistance to linezolid through mutations in the 50S large-subunit ribosomal proteins, such as L3. However, this mechanism is rarely reported in clinical enterococcal strains. Here, we describe a pair of Enterococcus faecium strains, 1505efm and 1583efm, isolated from a meningioma patient at different stages of linezolid treatment. Strain 1583efm, which was obtained after 17 days of linezolid treatment, exhibited an eightfold higher linezolid MIC (64 mg/L) than the initially isolated strain 1505efm (8 mg/L). Meanwhile, 1583efm became susceptible to erythromycin, tetracycline, and high-level streptomycin due to the loss of plasmid-borne resistance genes erm(A), erm(B), tet(M), ant(6)-Ia, and aph(3')-III. Whole-genome comparison revealed a deletion in the rplC gene of 1583efm, resulting in the loss of 21 amino acids (∆Tyr139-Arg159) in ribosomal protein L3. Structural modeling showed that this deletion disrupts the linezolid hydrogen bond network near the ribosomal peptidyl transferase center, reducing its binding affinity. The mutation, which remained stable over 50 generations without antibiotics, imposed a significant fitness cost on the bacterial cells and led to an increase in the expression of the truncated rplC gene. Our study uncovers a novel linezolid resistance mechanism involving the deletion of ribosomal protein L3 in clinical E. faecium strains within the host.
Competing Interests: The authors declare no conflict of interest.
References: Antibiotics (Basel). 2021 Feb 22;10(2):. (PMID: 33671753)
Antimicrob Agents Chemother. 2015;59(6):3518-28. (PMID: 25845869)
Sci Rep. 2019 Dec 27;9(1):20149. (PMID: 31882834)
Antimicrob Agents Chemother. 2024 May 2;68(5):e0115923. (PMID: 38506549)
BMC Genomics. 2008 Feb 08;9:75. (PMID: 18261238)
PLoS Comput Biol. 2022 Jan 24;18(1):e1009802. (PMID: 35073327)
PLoS Comput Biol. 2018 Oct 18;14(10):e1006541. (PMID: 30335785)
Antimicrob Agents Chemother. 2015 Oct;59(10):6256-61. (PMID: 26248384)
J Antimicrob Chemother. 2018 Jul 1;73(7):1880-1887. (PMID: 29659858)
RNA. 2003 Aug;9(8):982-92. (PMID: 12869709)
J Antimicrob Chemother. 2022 Sep 30;77(10):2596-2621. (PMID: 35989417)
Antimicrob Agents Chemother. 2003 Sep;47(9):2892-6. (PMID: 12936991)
Mol Cell. 2007 Mar 23;25(6):877-88. (PMID: 17386264)
Clin Infect Dis. 2006 Jul 15;43(2):165-71. (PMID: 16779742)
BMC Infect Dis. 2024 May 10;24(1):486. (PMID: 38730362)
APMIS. 2002 Dec;110(12):869-74. (PMID: 12645665)
Nucleic Acids Res. 2023 Jul 5;51(W1):W484-W492. (PMID: 37140037)
J Antimicrob Chemother. 2018 Sep 1;73(9):2314-2322. (PMID: 29878213)
J Antimicrob Chemother. 2017 Feb;72(2):354-364. (PMID: 27999068)
J Antimicrob Chemother. 2010 Mar;65(3):442-5. (PMID: 20089543)
Antimicrob Agents Chemother. 2007 Jun;51(6):2048-52. (PMID: 17404009)
Lancet. 2001 Jul 21;358(9277):207-8. (PMID: 11476839)
Microbiol Mol Biol Rev. 2021 Dec 15;85(4):e0010421. (PMID: 34756086)
Antimicrob Agents Chemother. 2007 Apr;51(4):1534-6. (PMID: 17242139)
Mol Microbiol. 2007 Jun;64(6):1506-14. (PMID: 17555436)
J Chem Theory Comput. 2016 Jan 12;12(1):281-96. (PMID: 26584231)
Nat Struct Mol Biol. 2022 Feb;29(2):162-171. (PMID: 35165456)
Clin Microbiol Rev. 2021 Jun 16;34(3):e0018820. (PMID: 34076490)
Crit Rev Biochem Mol Biol. 2005 Sep-Oct;40(5):285-311. (PMID: 16257828)
Trends Microbiol. 2015 Jul;23(7):401-7. (PMID: 25818802)
J Chem Theory Comput. 2023 Aug 22;19(16):5503-5515. (PMID: 37493980)
J Antimicrob Chemother. 2020 Jul 1;75(7):1699-1703. (PMID: 32277823)
Infect Drug Resist. 2022 Jan 04;15:13-20. (PMID: 35018102)
J Antimicrob Chemother. 2015 Aug;70(8):2182-90. (PMID: 25977397)
Diagn Microbiol Infect Dis. 2010 Sep;68(1):34-9. (PMID: 20727467)
Antimicrob Agents Chemother. 2010 Feb;54(2):742-8. (PMID: 19933808)
J Antimicrob Chemother. 2018 Jul 1;73(7):1763-1769. (PMID: 29635422)
Infect Drug Resist. 2020 Aug 04;13:2711-2716. (PMID: 32801805)
Emerg Infect Dis. 2007 Jul;13(7):1024-30. (PMID: 18214174)
J Antimicrob Chemother. 2020 Feb 1;75(2):283-291. (PMID: 31742612)
Ann Clin Microbiol Antimicrob. 2024 May 4;23(1):41. (PMID: 38704577)
Microb Genom. 2023 Jul;9(7):. (PMID: 37410656)
J Clin Microbiol. 2013 Apr;51(4):1256-9. (PMID: 23345292)
Proc Natl Acad Sci U S A. 2016 Oct 25;113(43):12150-12155. (PMID: 27791002)
Antimicrob Agents Chemother. 2009 Dec;53(12):5265-74. (PMID: 19752277)
N Engl J Med. 2002 Mar 14;346(11):867-9. (PMID: 11893808)
Clin Infect Dis. 2017 Nov 29;65(12):2159-2160. (PMID: 29020204)
J Clin Microbiol. 2010 Aug;48(8):3041-3. (PMID: 20519471)
Antimicrob Agents Chemother. 2012 Feb;56(2):603-12. (PMID: 22143525)
Antimicrob Agents Chemother. 2011 Apr;55(4):1684-92. (PMID: 21263048)
Clin Infect Dis. 2002 Nov 15;35(10):1269-72. (PMID: 12410489)
Lancet. 2001 Dec 8;358(9297):1975-82. (PMID: 11747939)
Ann Lab Med. 2019 Jan;39(1):36-42. (PMID: 30215228)
Grant Information: 20211231Y156 Guidance Project of Agriculture and Social Development from Hangzhou Municipal Science & Technology Bureau; 82002169 National Natural Science Foundation of China
Contributed Indexing: Keywords: Enterococcus faecium; linezolid resistance; ribosomal protein L3; rplC
Molecular Sequence: Protein 7NHK; 7S1H
Substance Nomenclature: ISQ9I6J12J (Linezolid)
0 (Ribosomal Proteins)
0 (Anti-Bacterial Agents)
0 (Ribosomal Protein L3)
0 (Bacterial Proteins)
0 (RPL3 protein, human)
Entry Date(s): Date Created: 20251028 Date Completed: 20251210 Latest Revision: 20260513
Update Code: 20260514
PubMed Central ID: PMC12691684
DOI: 10.1128/aac.00871-25
PMID: 41147723
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:1098-6596
DOI:10.1128/aac.00871-25