دورية أكاديمية

Genetic characterization of tigecycline resistance in clinical isolates of Enterobacter cloacae and Enterobacter aerogenes

التفاصيل البيبلوغرافية
العنوان: Genetic characterization of tigecycline resistance in clinical isolates of Enterobacter cloacae and Enterobacter aerogenes
المؤلفون: Veleba, Mark, De Majumdar, Shyamasree, Hornsey, Michael, Woodford, Neil, Schneiders, Thamarai
بيانات النشر: Oxford University Press
سنة النشر: 2013
المجموعة: HighWire Press (Stanford University)
مصطلحات موضوعية: Original research
الوصف: Objectives The intrinsically encoded ramA gene has been linked to tigecycline resistance through the up-regulation of efflux pump AcrAB in Enterobacter cloacae . The molecular basis for increased ramA expression in E. cloacae and Enterobacter aerogenes , as well as the role of AraC regulator rarA , has not yet been shown. To ascertain the intrinsic molecular mechanism(s) involved in tigecycline resistance in Enterobacter spp., we analysed the expression levels of ramA and rarA and corresponding efflux pump genes acrAB and oqxAB in Enterobacter spp. clinical isolates. Methods The expression levels of ramA , rarA , oqxA and acrA were tested by quantitative real-time RT–PCR. The ramR open reading frames of the ramA- overexpressing strains were sequenced; strains harbouring mutations were transformed with wild-type ramR to study altered ramA expression and tigecycline susceptibility. Results Tigecycline resistance was mediated primarily by increased ramA expression in E. cloacae and E. aerogenes . Only the ramA -overexpressing E. cloacae isolates showed increased rarA and oqxA expression. Upon complementation with wild-type ramR , all Enterobacter spp. containing ramR mutations exhibited decreased ramA and acrA expression and increased tigecycline susceptibility. Exceptions were one E. cloacae strain and one E. aerogenes strain, where a decrease in ramA levels was not accompanied by lower acrA expression. Conclusions Increased ramA expression due to ramR deregulation is the primary mediator of tigecycline resistance in clinical isolates of E. cloacae and E. aerogenes . However, some ramA- overexpressing isolates do not show changes in ramR , suggesting alternate pathways of ramA regulation; the rarA regulator and the oqxAB efflux pump may also play a role in tigecycline resistance in E. cloacae .
نوع الوثيقة: text
وصف الملف: text/html
اللغة: English
العلاقة: http://jac.oxfordjournals.org/cgi/content/short/dks530v1Test; http://dx.doi.org/10.1093/jac/dks530Test
DOI: 10.1093/jac/dks530
الإتاحة: https://doi.org/10.1093/jac/dks530Test
http://jac.oxfordjournals.org/cgi/content/short/dks530v1Test
حقوق: Copyright (C) 2013, The British Society for Antimicrobial Chemotherapy
رقم الانضمام: edsbas.B0EF1591
قاعدة البيانات: BASE