Alternative vanHAX promoters and increased vanA-plasmid copy number resurrect silenced glycopeptide resistance in Enterococcus faecium

التفاصيل البيبلوغرافية
العنوان: Alternative vanHAX promoters and increased vanA-plasmid copy number resurrect silenced glycopeptide resistance in Enterococcus faecium
المؤلفون: Jessin Janice, Ingegerd Sjögren, Arnfinn Sundsfjord, Audun Sivertsen, Theresa Wagner, Kristin Hegstad
المصدر: Journal of Antimicrobial Chemotherapy
بيانات النشر: Oxford University Press, 2020.
سنة النشر: 2020
مصطلحات موضوعية: Microbiology (medical), DNA Copy Number Variations, Operon, Enterococcus faecium, Microbial Sensitivity Tests, Microbiology, Plasmid, Bacterial Proteins, medicine, Humans, AcademicSubjects/MED00740, Pharmacology (medical), Gram-Positive Bacterial Infections, Original Research, Pharmacology, Sweden, biology, Teicoplanin, Glycopeptides, Promoter, VDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, Glycopeptide, VDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710, Anti-Bacterial Agents, Infectious Diseases, AcademicSubjects/MED00290, Enterococcus, Vancomycin, AcademicSubjects/MED00230, medicine.drug, Plasmids
الوصف: Background Vancomycin variable enterococci (VVE) are van-positive isolates with a susceptible phenotype that can convert to a resistant phenotype during vancomycin selection. Objectives To describe a vancomycin-susceptible vanA-PCR positive ST203 VVE Enterococcus faecium isolate (VVESwe-S) from a liver transplantation patient in Sweden which reverted to resistant (VVESwe-R) during in vitro vancomycin exposure. Methods WGS analysis revealed the genetic differences between the isolates. Expression of the van-operon was investigated by qPCR. Fitness and stability of the revertant were investigated by growth measurements, competition and serial transfer. Results The VVESwe-R isolate gained high-level vancomycin (MIC >256 mg/L) and teicoplanin resistance (MIC = 8 mg/L). VVESwe-S has a 5′-truncated vanR activator sequence and the VVESwe-R has in addition acquired a 44 bp deletion upstream of vanHAX in a region containing alternative putative constitutive promoters. In VVESwe-R the vanHAX-operon is constitutively expressed at a level comparable to the non-induced prototype E. faecium BM4147 strain. The vanHAX operon of VVESwe is located on an Inc18-like plasmid, which has a 3–4-fold higher copy number in VVESwe-R compared with VVESwe-S. Resistance has a low fitness cost and the vancomycin MIC of VVESwe-R decreased during in vitro serial culture without selection. The reduction in MIC was associated with a decreased vanA-plasmid copy number. Conclusions Our data support a mechanism by which vancomycin-susceptible VVE strains may revert to a resistant phenotype through the use of an alternative, constitutive, vanR-activator-independent promoter and a vanA-plasmid copy number increase.
اللغة: English
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cf55b362c0fee86ce674c1fc42ffc350
https://hdl.handle.net/10037/20433
Rights: OPEN
رقم الانضمام: edsair.doi.dedup.....cf55b362c0fee86ce674c1fc42ffc350
قاعدة البيانات: OpenAIRE