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Volume 72, Issue 7

Multiple mechanisms of linezolid resistance in detected by whole-genome sequencing No Access

Abstract

Linezolid is an effective therapeutic option for treating severe infections caused by multidrug-resistant Gram-positive organisms. Several mechanisms have been reported to be responsible for resistance to this antibiotic.

Although several mechanisms of linezolid resistance have been reported in , the prevalence and potential for horizontal transfer of resistance genes have not been fully characterized, particularly among isolates from India.

To perform whole-genome sequencing (WGS) of linezolid-resistant isolates to characterize the resistance mechanisms.

WGS was performed for 16 linezolid-resistant isolates to check for the presence of , and genes and mutations in 23S rRNA and ribosomal proteins (L3, L4 and L22) that are possible mechanisms implicated in linezolid resistance. Sequence types were identified using MLST finder. The minimum inhibitory concentration (MIC) of linezolid was determined using the E-test method. Polymerase chain reaction (PCR) was carried out for the detection of the gene.

The study documented three different mechanisms of linezolid resistance in . Thirteen of the 16 isolates were phenotypically resistant to linezolid, of which 12 were positive for the gene. The G2603T mutation in 23S rRNA was found in the majority of the isolates (=13). Ten isolates had the R138V mutation in L3 ribosomal protein. Twelve isolates with the gene in combination with either G2603T or R138V mutations displayed extremely high MIC values. Surprisingly, three phenotypically sensitive isolates were found to be positive for the gene but negative for other resistance mechanisms. Importantly, in almost half of the isolates the gene was present on a plasmid. ST3 and ST1 were found to be the predominant sequence types.

All phenotypically resistant isolates exhibited two or three linezolid resistance mechanisms. The gene was found on plasmids in many isolates, demonstrating its potential for horizontal transfer to more pathogenic organisms.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): cfr gene , G2603T mutation , linezolid resistance and S. haemolyticus
Funding
This study was supported by the:
  • Indian Council of Medical Research
    • Principle Award Recipient: SujathaSistla
  • Jawaharlal Institute Of Postgraduate Medical Education and Research
    • Principle Award Recipient: MeerabaiManoharan
© 2023 The Authors
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/content/journal/jmm/10.1099/jmm.0.001737
2023-07-21
2024-05-21
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Multiple mechanisms of linezolid resistance in Staphylococcus haemolyticus detected by whole-genome sequencing
J. Med. Microbiol. 72, 001737 (2023); https://doi.org/10.1099/jmm.0.001737
/content/journal/jmm/10.1099/jmm.0.001737
/content/journal/jmm/10.1099/jmm.0.001737
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