Expression of AraC/XylS stress response regulators in two distinct carbapenem-resistant Enterobacter cloacae ST89 biotypes. (20th January 2020)

• Record Type: Journal Article
• Authors: Majewski, Piotr; Gutowska, Anna; Sacha, Pawel; Schneiders, Thamarai; Talalaj, Mariola; Majewska, Paulina; Zebrowska, Agnieszka; Ojdana, Dominika; Wieczorek, Piotr; Hauschild, Tomasz; Kowalczuk, Oksana; Niklinski, Jacek; Radziwon, Piotr; Tryniszewska, Elzbieta
• Is Part Of: Journal of antimicrobial chemotherapy. Volume 75:Number 5(2020)
• Page Start: 1146
• Page End: 1150
• Publication Date: 2020-01-20
• Subjects: Anti-infective agents -- Periodicals; Chemotherapy -- Periodicals; 615.58
• DOI: 10.1093/jac/dkz569
• Languages: English
• ISSNs: 0305-7453

Abstract

Abstract: Background: The growing incidence of MDR Gram-negative bacteria is a rapidly emerging challenge in modern medicine. Objectives: We sought to establish the role of intrinsic drug-resistance regulators in combination with specific genetic mutations in 11 Enterobacter cloacae isolates obtained from a single patient within a 7 week period. Methods: The molecular characterization of eight carbapenem-resistant and three carbapenem-susceptible E. cloacae ST89 isolates included expression-level analysis and WGS. Quantitative PCR included: (i) chromosomal cephalosporinase gene ( ampC ); (ii) membrane permeability factor genes, e.g. ompF, ompC, acrA, acrB and tolC ; and (iii) intrinsic regulatory genes, e.g. ramA, ampR, rob, marA and soxS, which confer reductions in antibiotic susceptibility. Results: In this study we describe the influence of the alterations in membrane permeability ( ompF and ompC levels), intrinsic regulatory genes ( ramA, marA, soxS ) and intrinsic chromosomal cephalosporinase AmpC on reductions in carbapenem susceptibility of E. cloacae clinical isolates. Interestingly, only the first isolate possessed the acquired VIM-4 carbapenemase, which has been lost in subsequent isolates. The remaining XDR E. cloacae ST89 isolates presented complex carbapenem-resistance pathways, which included perturbations in permeability of bacterial membranes mediated by overexpression of ramA, encoding an AraC/XylS global regulator. Moreover, susceptible isolates differed significantly from other isolates in terms of marA down-regulation and soxS up-regulation. Conclusions: Molecular mechanisms of resistance among carbapenem-resistant E. cloacae included production of acquired VIM-4 carbapenemase, significant alterations in membrane permeability due to increased expression of ramA, encoding an AraC/XylS global regulator, and the overproduction of chromosomal AmpC cephalosporinase.