Small RNAs in vancomycin-resistant Enterococcus faecium involved in daptomycin response and resistance

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作者：
Clara Sinel
Yoann Augagneur
Mohamed Sassi
Julie Bronsard
Margherita Cacaci
François Guérin
Maurizio Sanguinetti
Pierrick Meignen
Vincent Cattoir
Brice Felden
机构：
[1] University of Caen Normandie,
[2] Inserm U1230-Biochimie pharmaceutique,undefined
[3] Rennes University,undefined
[4] Catholic University of Sacred Heart,undefined
[5] Institute of Microbiology,undefined
[6] Caen University Hospital,undefined
[7] Department of Clinical Microbiology,undefined
[8] University of Caen Normandie,undefined
[9] IUT (department “STID”),undefined
[10] National Reference Center for Antimicrobial Resistance (lab Enterococci),undefined
[11] Inserm U1230-Biochimie pharmaceutique,undefined
[12] Rennes University,undefined
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Scientific Reports | / 7卷
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摘要：
Vancomycin-resistant Enterococcus faecium is a leading cause of hospital-acquired infections and outbreaks. Regulatory RNAs (sRNAs) are major players in adaptive responses, including antibiotic resistance. They were extensively studied in gram-negative bacteria, but less information is available for gram-positive pathogens. No sRNAs are described in E. faecium. We sought to identify a set of sRNAs expressed in vancomycin-resistant E. faecium Aus0004 strain to assess their roles in daptomycin response and resistance. Genomic and transcriptomic analyses revealed a set of 61 sRNA candidates, including 10 that were further tested and validated by Northern and qPCR. RNA-seq was performed with and without subinhibitory concentrations (SICs) of daptomycin, an antibiotic used to treat enterococcal infections. After daptomycin SIC exposure, the expression of 260 coding and srna genes was altered, with 80 upregulated and 180 downregulated, including 51% involved in carbohydrate and transport metabolisms. Daptomycin SIC exposure significantly affected the expression of seven sRNAs, including one experimentally confirmed, sRNA_0160. We studied sRNA expression in isogenic mutants with increasing levels of daptomycin resistance and observed that expression of several sRNAs, including sRNA_0160, was modified in the stepwise mutants. This first genome-wide sRNA identification in E. faecium suggests that some sRNAs are linked to antibiotic stress response and resistance.
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