| Autor: |
Reyes-Fernández EZ; Department Biological Chemistry, Institute of Life Sciences, Silberman Bldg. 1-339, Edmond J. Safra Campus, Hebrew University of Jerusalem, Givat Ram, Jerusalem, 91904, Israel., Schuldiner S; Department Biological Chemistry, Institute of Life Sciences, Silberman Bldg. 1-339, Edmond J. Safra Campus, Hebrew University of Jerusalem, Givat Ram, Jerusalem, 91904, Israel. shimon.schuldiner@huji.ac.il. |
| Jazyk: |
angličtina |
| Zdroj: |
Scientific reports [Sci Rep] 2020 Jun 19; Vol. 10 (1), pp. 9954. Date of Electronic Publication: 2020 Jun 19. |
| DOI: |
10.1038/s41598-020-66890-1 |
| Abstrakt: |
Awareness of the problem of antimicrobial resistance (AMR) has escalated, and drug-resistant infections are named among the most urgent issues facing clinicians today. Bacteria can acquire resistance to antibiotics by a variety of mechanisms that, at times, involve changes in their metabolic status, thus altering diverse biochemical reactions, many of them pH-dependent. In this work, we found that modulation of the cytoplasmic pH (pH i ) of Escherichia coli provides a thus far unexplored strategy to support resistance. We show here that the acidification of the cytoplasmic pH is a previously unrecognized consequence of the activation of the marRAB operon. The acidification itself contributes to the full implementation of the resistance phenotype. We measured the pH i of two resistant strains, developed in our laboratory, that carry mutations in marR that activate the marRAB operon. The pH i of both strains is lower than that of the wild type strain. Inactivation of the marRAB response in both strains weakens resistance, and pH i increases back to wild type levels. Likewise, we showed that exposure of wild type cells to weak acids that caused acidification of the cytoplasm induced a resistant phenotype, independent of the marRAB response. We speculate that the decrease of the cytoplasmic pH brought about by activation of the marRAB response provides a signaling mechanism that modifies metabolic pathways and serves to cope with stress and to lower metabolic costs. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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