Dataset Information

First Insight into the Genome Sequences of Two Linezolid-Resistant Nocardia farcinica Strains Isolated from Patients with Cystic Fibrosis.

ABSTRACT: The draft genome sequences of two Nocardia farcinica strains isolated from two patients with cystic fibrosis (CF), resistant to trimethoprim/sulfamethoxazole and linezolid, are reported here. The estimated genome sizes were 5.8 Mb with a 70.63% G+C content. Transposases from Tn916 were detected, but not 23S rRNA mutation (G2576T) related to linezolid resistance.

SUBMITTER: Valdezate S

PROVIDER: S-EPMC5690327 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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First Insight into the Genome Sequences of Two Linezolid-Resistant Nocardia farcinica Strains Isolated from Patients with Cystic Fibrosis.

Valdezate Sylvia S Monzón Sara S Garrido Noelia N Zaballos Angel A Medina-Pascual María J MJ Azcona-Gutiérrez José M JM Vilar Begoña B Cuesta Isabel I

Genome announcements 20171116 46

The draft genome sequences of two Nocardia farcinica strains isolated from two patients with cystic fibrosis (CF), resistant to trimethoprim/sulfamethoxazole and linezolid, are reported here. The estimated genome sizes were 5.8 Mb with a 70.63% G+C content. Transposases from Tn916 were detected, but not 23S rRNA mutation (G2576T) related to linezolid resistance. ...[more]

PMID: 29146850

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Project description:Linezolid is an antibiotic used to treat serious Staphylococcus aureus infections. Resistance to linezolid is considered rare but could emerge with repeated dosing. We recently reported widespread prescription of linezolid for a cohort of patients with cystic fibrosis (CF). The goals of this study were to determine the incidence of linezolid-resistant methicillin-resistant Staphylococcus aureus (MRSA) in CF and identify molecular mechanisms for linezolid resistance. We identified patients who cultured S. aureus resistant to linezolid with minimum inhibitory concentration (MIC) >4 at the University of Iowa CF Center between 2008 and 2018. We obtained isolates from these patients and retested susceptibility to linezolid using broth microdilution. We used whole genome sequencing to perform phylogenetic analysis of linezolid-resistant isolates and examine sequences for mutations or accessory genes that confer linezolid resistance. Between 2008 and 2018, 111 patients received linezolid, and 4 of these patients cultured linezolid-resistant S. aureus. We sequenced 11 resistant and 21 susceptible isolates from these 4 subjects. Phylogenetic analysis indicated that linezolid resistance developed in ST5 or ST105 backgrounds. Three individuals had linezolid-resistant S. aureus with a G2576T mutation in 23S rRNA. One of these subjects additionally had a mutS- mutL- hypermutating S. aureus that produced five resistant isolates with multiple ribosomal subunit mutations. In one subject, the genetic basis for linezolid resistance was unclear. We conclude that linezolid resistant S. aureus can occur through multiple genetic mechanisms in patients with repeated exposure to this antibiotic. IMPORTANCE Patients with cystic fibrosis have persistent lung infections with Staphylococcus aureus that require extensive antibiotic treatments. Linezolid, an antibiotic given by oral or intravenous route, is prescribed repeatedly for patients whose lung disease has progressed. After treatment with linezolid, S. aureus strains can evolve antibiotic resistance through multiple genetic mechanisms. In addition to a common mutation in the 23S ribosomal RNA known to confer linezolid resistance, S. aureus strains can evolve novel resistance based on a combination of mutations affecting the bacterial ribosome. This combination of mutations was observed in a strain that exhibited hypermutation owing to the loss of the DNA repair genes mutS and mutL. In this cohort of patients with cystic fibrosis, linezolid resistance was transient, possibly due to the growth disadvantage of resistant strains. However, ongoing chronic exposure to linezolid may create optimal conditions for the future emergence of resistance to this critical antibiotic.

Dataset Information

First Insight into the Genome Sequences of Two Linezolid-Resistant Nocardia farcinica Strains Isolated from Patients with Cystic Fibrosis.

Publications

First Insight into the Genome Sequences of Two Linezolid-Resistant <i>Nocardia farcinica</i> Strains Isolated from Patients with Cystic Fibrosis.

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