Jun 23 2022 Hfq, Crc, and antibiotic resistance in P. aeruginosa

Here we study carbon catabolite repression (CCR) and its impact on antibiotic susceptibility in Pseudomonas aeruginosa

Schematic of the mexGHI-opmD operon downregulation by Hfq during carbon catabolite repression

This study on Pseudomonas aeruginosa underscores the interplay between microbial metabolism and antibiotic resistance, which has implications for human, animal, and environmental health. The observed link between carbon catabolite repression (CCR) and antibiotic susceptibility suggests that the microbial response to environmental nutrients can impact the efficacy of antibiotics. This insight is crucial as antibiotic-resistant strains can pose threats to both human healthcare and animal husbandry. Understanding such regulatory mechanisms can guide the development of targeted interventions, aligning with the One Health approach that seeks to optimize health outcomes across different domains of the ecosystem.

Abstract

In Pseudomonas aeruginosa, the RNA chaperone Hfq and the catabolite repression protein Crc act in concert to regulate numerous genes during carbon catabolite repression (CCR). After alleviation of CCR, the RNA CrcZ sequesters Hfq/Crc, which leads to a rewiring of gene expression to ensure the consumption of less preferred carbon and nitrogen sources. Here, we performed a multiomics approach by assessing the transcriptome, translatome, and proteome in parallel in P. aeruginosa strain O1 during and after relief of CCR. As Hfq function is impeded by the RNA CrcZ upon relief of CCR, and Hfq is known to impact antibiotic susceptibility in P. aeruginosa, emphasis was laid on links between CCR and antibiotic susceptibility. To this end, we show that the mexGHI-opmD operon encoding an efflux pump for the antibiotic norfloxacin and the virulence factor 5-Methyl-phenazine is upregulated after alleviation of CCR, resulting in a decreased susceptibility to the antibiotic norfloxacin. A model for indirect regulation of the mexGHI-opmD operon by Hfq is presented.

Citation

Rewiring of Gene Expression in Pseudomonas aeruginosa During Diauxic Growth Reveals an Indirect Regulation of the MexGHI-OpmD Efflux Pump by Hfq
Marlena Rozner, Ella Nukarinen, Michael T. Wolfinger, Fabian Amman, Wolfram Weckwerth, Udo Blaesi, Elisabeth Sonnleitner
Front. Microbiol. (2022) 13:919539 | doi:10.3389/fmicb.2022.919539 | PDF