ArticleAntimicrobial agents and chemotherapy2014
Metabolic compensation of fitness costs associated with overexpression of the multidrug efflux pump MexEF-OprN in Pseudomonas aeruginosa.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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33 citing papers in PubMed, 62 citations in OpenAlex.
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- Metabolic specialization drives reduced pathogenicity in Pseudomonas aeruginosa isolates from cystic fibrosis patients.PLoS biology · 2024Article
- Preserving the efficacy of antibiotics to tackle antibiotic resistance.Microbial biotechnology · 2024Review
- Improving 5-(hydroxymethyl)furfural (HMF) tolerance ofMetabolic engineering communications · 2024Article
- Sub-inhibitory antibiotic treatment selects for enhanced metabolic efficiency.Microbiology spectrum · 2024Article
- Review
- The balance between antibiotic resistance and fitness/virulence inFrontiers in microbiology · 2023Review
- Evolution of Habitat-Dependent Antibiotic Resistance in Pseudomonas aeruginosa.Microbiology spectrum · 2022Article
- Decreased thermal niche breadth as a trade-off of antibiotic resistance.The ISME journal · 2022Article
- The role of chemotaxis and efflux pumps on nitrate reduction in the toxic regions of a ciprofloxacin concentration gradient.The ISME journal · 2021Article
- Antibiotic resistance: Time of synthesis in a post-genomic age.Computational and structural biotechnology journal · 2021Review
- Serum-Associated Antibiotic Tolerance in Pediatric Clinical Isolates of Pseudomonas aeruginosa.Journal of the Pediatric Infectious Diseases Society · 2020Article
- Antibiotic Resistance: Moving From Individual Health Norms to Social Norms in One Health and Global Health.Frontiers in microbiology · 2020Review
- Variation of Burkholderia cenocepacia cell wall morphology and mechanical properties during cystic fibrosis lung infection, assessed by atomic force microscopy.Scientific reports · 2019Article
- Adapting to the Airways: Metabolic Requirements ofMetabolites · 2019Review
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3 authors at 1 institution in 1 country.
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Abstract
The acquisition of antibiotic resistance has been associated with a possible nonspecific, metabolic burden that is reflected in decreased fitness among resistant bacteria. We have recently demonstrated that overexpression of the MexEF-OprN multidrug efflux pump does not produce a metabolic burden when measured by classical competitions tests but rather leads to a number of changes in the organism's physiology. One of these changes is the untimely activation of the nitrate respiratory chain under aerobic conditions. MexEF-OprN is a proton/substrate antiporter. Overexpression of this element should result in a constant influx of protons, which may lead to cytoplasmic acidification. Acidification was not observed in aerobiosis, a situation in which the MexEF-overproducing mutant increases oxygen consumption. This enhanced oxygen uptake serves to eliminate intracellular proton accumulation, preventing the cytoplasmic acidification that was observed exclusively under anaerobic conditions, a situation in which the fitness of the MexEF-OprN-overproducing mutant decreases. Finally, we determined that the early activation of the nitrate respiratory chain under aerobic conditions plays a role in preventing a deleterious effect associated with the overexpression of MexEF-OprN. Our results show that metabolic rewiring may assist in overcoming the potential fitness cost associated with the acquisition of antibiotic resistance. Furthermore, the capability to metabolically compensate for this effect is habitat dependent, as demonstrated by our results under anaerobic conditions. The development of drugs that prevent metabolic compensation of fitness costs may help to reduce the persistence and dissemination of antibiotic resistance.
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