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Global gene expression profiling and antibiotic susceptibility after repeated exposure to the carbon monoxide-releasing molecule-2 (CORM-2) in multidrug-resistant ESBL-producing uropathogenic Escherichia coli
Örebro University, School of Health Sciences. (iRiSC—Inflammatory Response and Infection Susceptibility Centre)
Örebro University, School of Medical Sciences.
Örebro University, School of Medical Sciences.
Örebro University, School of Medical Sciences. (iRiSC—Inflammatory Response and Infection Susceptibility Centre)
2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 6, e0178541Article in journal (Refereed) Published
Abstract [en]

Treatment of urinary tract infections is today a challenge due to the increasing prevalence of multidrug-resistant ESBL-producing uropathogenic Escherichia coli (UPEC). There is an urgent need for new treatment strategies for multidrug-resistant UPEC and preferably with targets that have low potential for development of resistance. Carbon monoxide-releasing molecules (CORMs) are novel and potent antibacterial agents. The present study examines the transcriptomic targets of CORM-2 in a multidrug-resistant ESBL-producing UPEC isolate in response to a single exposure to CORM-2 and after repeated exposure to CORM-2. The bacterial viability and minimal inhibitory concentration (MIC) were also examined after repeated exposure to CORM-2. Microarray analysis revealed that a wide range of processes were affected by CORM-2, including a general trend of down-regulation in energy metabolism and biosynthesis pathways and up-regulation of the SOS response and DNA repair. Several genes involved in virulence (ibpB), antibiotic resistance (marAB, mdtABC) and biofilm formation (bhsA, yfgF) were up-regulated, while some genes involved in virulence (kpsC, fepCEG, entABE), antibiotic resistance (evgA) and biofilm formation (artIP) were down-regulated. Repeated exposure to CORM-2 did not alter the gene expression patterns, the growth inhibitory response to CORM-2 or the MIC values for CORM-2, cefotaxime, ciprofloxacin and trimethoprim. This study identifies several enriched gene ontologies, modified pathways and single genes that are targeted by CORM-2 in a multidrug-resistant UPEC isolate. Repeated exposure to CORM-2 did not change the gene expression patterns or fold changes and the susceptibility to CORM-2 remained after repeated exposure.

Place, publisher, year, edition, pages
Public Library of Science , 2017. Vol. 12, no 6, e0178541
National Category
Microbiology
Research subject
Biomedicine
Identifiers
URN: urn:nbn:se:oru:diva-58779DOI: 10.1371/journal.pone.0178541ISI: 000402880700036PubMedID: 28591134Scopus ID: 2-s2.0-85020463890OAI: oai:DiVA.org:oru-58779DiVA: diva2:1128573
Note

Funding Agencies:

Faculty of Medicine and Health at Örebro University  

Nyckelfonden at Örebro University Hospital 

Available from: 2017-07-26 Created: 2017-07-26 Last updated: 2017-10-05Bibliographically approved

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