Linezolid resistance in Staphylococcus epidermidis associated with a G2603T mutation in the 23S rRNA gene

Lincopán, Nilton; Almeida, Lara Mendes de; Araújo, Maria; Mamizuka, Elsa Masae

doi:10.1016/j.ijantimicag.2009.02.023

Cited by 27 publications

(21 citation statements)

References 6 publications

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“…Although the U2504A mutation has been reported in clinical staphylococcal isolates (16,48,97), the only U2504 mutation isolated from in vitro selection with linezolid to date is U2504C (41,50). Additional mutated positions of 23S rRNA at G2603U (49,78,83) and C2534U (97) have been reported in clinical isolates with reduced linezolid susceptibility, but a direct relationship between these mutations and linezolid resistance is unclear.…”

Section: Resistance Caused By 23s Rrna Mutationsmentioning

confidence: 99%

Resistance to Linezolid Caused by Modifications at Its Binding Site on the Ribosome

Long

Vester

2012

Antimicrob Agents Chemother

313

195

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Linezolid is an oxazolidinone antibiotic in clinical use for the treatment of serious infections of resistant Gram-positive bacteria. It inhibits protein synthesis by binding to the peptidyl transferase center on the ribosome. Almost all known resistance mechanisms involve small alterations to the linezolid binding site, so this review will therefore focus on the various changes that can adversely affect drug binding and confer resistance. High-resolution structures of linezolid bound to the 50S ribosomal subunit show that it binds in a deep cleft that is surrounded by 23S rRNA nucleotides. Mutation of 23S rRNA has for some time been established as a linezolid resistance mechanism. Although ribosomal proteins L3 and L4 are located further away from the bound drug, mutations in specific regions of these proteins are increasingly being associated with linezolid resistance. However, very little evidence has been presented to confirm this. Furthermore, recent findings on the Cfr methyltransferase underscore the modification of 23S rRNA as a highly effective and transferable form of linezolid resistance. On a positive note, detailed knowledge of the linezolid binding site has facilitated the design of a new generation of oxazolidinones that show improved properties against the known resistance mechanisms. LINEZOLID

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Section: Resistance Caused By 23s Rrna Mutationsmentioning

confidence: 99%

Resistance to Linezolid Caused by Modifications at Its Binding Site on the Ribosome

Long

Vester

2012

Antimicrob Agents Chemother

313

195

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“…Since this report, an increasing number of studies showing this resistance among staphylococci have been published (3)(4)(5)(6). In Brazil, there are a few isolates that show resistance to linezolid, which are apparently sporadic (4,5,7,8).…”

mentioning

confidence: 97%

Emergence of methicillin‐resistant coagulase‐negative staphylococci resistant to linezolid with rRNA gene C2190T and G2603T mutations

Cidral¹,

Carvalho²,

Figueiredo³

et al. 2015

APMIS

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The aim of this article were to determinate the mechanism of linezolid resistance in coagulase-negative methicillin-resistant staphylococci from hospitals in the northeast of Brazil. We identified the isolates using VITEK(®) 2 and MALDI-TOF. Susceptibility to antibiotics was measured by the disk-diffusion method and by Etest(®) . Extraction of the whole genome DNA was performed, followed by screening of all the strains for the presence of mecA and cfr genes. The domain V region of 23S rRNA gene was sequenced and then aligned with a linezolid-susceptible reference strain. Pulsed-field gel electrophoresis (PFGE) macro-restriction analysis was performed. Three linezolid-resistant Staphylococcus hominis and two linezolid-resistant Staphylococcus epidermidis strains were analyzed. The isolates showed two point mutations in the V region of the 23S rRNA gene (C2190T and G2603T). We did not detect the cfr gene in any isolate by PCR. The S. hominis showed the same pulsotype, while the S. epidermidis did not present any genetic relation to each other. In conclusion, this study revealed three S. hominis and two S. epidermidis strains with resistance to linezolid due to a double mutation (C2190T and G2603T) in the domain V of the 23S rRNA gene. For the first time, the mutation of C2190T in S. epidermidis is described. This study also revealed the clonal spread of a S. hominis pulsotype between three public hospitals in the city of Natal, Brazil. These findings highlight the importance of continued vigilance of linezolid resistance in staphylococci.

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“…Both mutations have been very recently reported in clinical S. hominis in a hospital of southern Spain (Sorlozano et al, 2010). In addition, the G2603T mutation was found in a S. epidermidis strain isolated in Brazil (Lincopan et al, 2009). However, to our knowledge this is the first report in which the G2474T point mutation has been detected in domain V of the 23S rRNA gene of clinical S. epidermidis.…”

Section: Discussionmentioning

confidence: 60%

“…The substitution G2576T (Escherichia coli 23S rRNA gene numbering) is the most frequently detected (Tsiodras et al, 2001). Nevertheless, other very unusual point mutations have been described in sporadic cases, such as G2474T (Sorlozano et al, 2010), T2500A (Meka et al, 2004), T2504A (Liakopoulos et al, 2009), G2534T (Liakopoulos et al, 2010), or G2603T (Lincopan et al, 2009). Recently, a new mechanism mediated by the cfr gene, encoding a methyltransferase, has been described (Kehrenberg and Schwarz, 2006).…”

Section: Introductionmentioning

confidence: 99%

Nosocomial outbreak of methicillin- and linezolid-resistant Staphylococcus epidermidis associated with catheter-related infections in intensive care unit patients

Seral¹,

Sáenz²,

Algarate³

et al. 2011

International Journal of Medical Microbiology

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Linezolid resistance in Staphylococcus epidermidis associated with a G2603T mutation in the 23S rRNA gene

Cited by 27 publications

References 6 publications

Resistance to Linezolid Caused by Modifications at Its Binding Site on the Ribosome

Resistance to Linezolid Caused by Modifications at Its Binding Site on the Ribosome

Emergence of methicillin‐resistant coagulase‐negative staphylococci resistant to linezolid with rRNA gene C2190T and G2603T mutations

Nosocomial outbreak of methicillin- and linezolid-resistant Staphylococcus epidermidis associated with catheter-related infections in intensive care unit patients

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