Harnessing Metabolic Regulation to Increase Hfq-Dependent Antibiotic Susceptibility in .

Front Microbiol 2018 9;9:2709. Epub 2018 Nov 9.

Max F. Perutz Laboratories, Department of Microbiology, Immunobiology and Genetics, Vienna Biocenter, University of Vienna, Vienna, Austria.

The opportunistic human pathogen is responsible for ~ 10% of hospital-acquired infections worldwide. It is notorious for its high level resistance toward many antibiotics, and the number of multi-drug resistant clinical isolates is steadily increasing. A better understanding of the molecular mechanisms underlying drug resistance is crucial for the development of novel antimicrobials and alternative strategies such as enhanced sensitization of bacteria to antibiotics in use. In several uptake channels for amino-acids and carbon sources can serve simultaneously as entry ports for antibiotics. The respective genes are often controlled by carbon catabolite repression (CCR). We have recently shown that Hfq in concert with Crc acts as a translational repressor during CCR. This function is counteracted by the regulatory RNA CrcZ, which functions as a decoy to abrogate Hfq-mediated translational repression of catabolic genes. Here, we report an increased susceptibility of deletion strains to different classes of antibiotics. Transcriptome analyses indicated that Hfq impacts on different mechanisms known to be involved in antibiotic susceptibility, viz import and efflux, energy metabolism, cell wall and LPS composition as well as on the c-di-GMP levels. Furthermore, we show that sequestration of Hfq by CrcZ, which was over-produced or induced by non-preferred carbon-sources, enhances the sensitivity toward antibiotics. Thus, controlled synthesis of CrcZ could provide a means to (re)sensitize to different classes of antibiotics.

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Source
https://www.frontiersin.org/article/10.3389/fmicb.2018.02709
Publisher Site
http://dx.doi.org/10.3389/fmicb.2018.02709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6237836PMC
November 2018
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The Calgary biofilm device: new technology for rapid determination of antibiotic susceptibilities of bacterial biofilms
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