title: Altered Outer Membrane Transcriptome Balance with AmpC Overexpression in Carbapenem-ResistantEnterobacter cloacae.
abstract: The growing incidence of multidrug-resistant (MDR) bacteria is an emerging challenge in modern medicine. The utility of carbapenems, considered "last-line" agents in therapy of infections caused by MDR pathogens, is being diminished by the growing incidence of various resistance mechanisms.Enterobacter cloacaehave lately begun to emerge as an important pathogen prone to exhibiting multiple drug resistance. We aimed to investigate the molecular basis of carbapenem-resistance in 44E. cloacaeclinical strains resistant to at least one carbapenem, and 21 susceptible strains. Molecular investigation of 65 E. cloacae clinical strains was based on quantitative polymerase chain reaction (qPCR) allowing for amplification ofampC, ompF, andompCtranscripts, and analysis of nucleotide sequences of alleles included in MLST scheme. Co-operation of three distinct carbapenem resistance mechanisms has been reported-production of OXA-48 (5%), AmpC overproduction (97.7%), and alterations in outer membrane (OM) transcriptome balance. Carbapenem-resistantE. cloacaewere characterized by (1.) downregulation ofompFgene (53.4%), which encodes protein with extensive transmembrane channels, and (2.) the polarization of OM transcriptome-balance (79.1%), which was sloped towardompCgene, encoding proteins recently reported to possess restrictive transmembrane channels. Subpopulations of carbapenem-susceptible strains showed relatively high degrees of sequence diversity without predominant types. ST-89 clearly dominates among carbapenem-resistant strains (88.6%) suggesting clonal spread of resistant strains. The growing prevalence of pathogens resistant to all currently available antimicrobial agents heralds the potential risk of a future "post-antibiotic era." Great efforts need to be taken to explore the background of resistance to "last resort" antimicrobials.
authors.affiliation: Department of Microbiological Diagnostics and Infectious Immunology, Medical University of Bialystok Bialystok, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Majewski
authors.affiliation: Department of Microbiological Diagnostics and Infectious Immunology, Medical University of Bialystok Bialystok, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Wieczorek
authors.affiliation: Department of Microbiological Diagnostics and Infectious Immunology, Medical University of Bialystok Bialystok, Poland.
authors.forename: Dominika
authors.initials: D
authors.lastname: Ojdana
authors.affiliation: Department of Microbiological Diagnostics and Infectious Immunology, Medical University of Bialystok Bialystok, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Sieńko
authors.affiliation: Department of Clinical Molecular Biology, Medical University of Bialystok Bialystok, Poland.
authors.forename: Oksana
authors.initials: O
authors.lastname: Kowalczuk
authors.affiliation: Department of Microbiological Diagnostics and Infectious Immunology, Medical University of Bialystok Bialystok, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Sacha
authors.affiliation: Department of Clinical Molecular Biology, Medical University of Bialystok Bialystok, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Nikliński
authors.affiliation: Department of Microbiological Diagnostics and Infectious Immunology, Medical University of Bialystok Bialystok, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Tryniszewska
keywords: AmpC; Enterobacter cloacae; MLST; carbapenem-resistance; outer membrane permeability