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Keywords = effluxome

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20 pages, 2152 KB  
Article
Mutation Analysis in Regulator DNA-Binding Regions for Antimicrobial Efflux Pumps in 17,000 Pseudomonas aeruginosa Genomes
by María Pérez-Vázquez, Carla López-Causapé, Andrés Corral-Lugo, Michael J. McConnell, Jesús Oteo-Iglesias, Antonio Oliver and Antonio J. Martín-Galiano
Microorganisms 2023, 11(10), 2486; https://doi.org/10.3390/microorganisms11102486 - 4 Oct 2023
Viewed by 2369
Abstract
Mutations leading to upregulation of efflux pumps can produce multiple drug resistance in the pathogen Pseudomonas aeruginosa. Changes in their DNA binding regions, i.e., palindromic operators, can compromise pump depression and subsequently enhance resistance against several antibacterials and biocides. Here, we have [...] Read more.
Mutations leading to upregulation of efflux pumps can produce multiple drug resistance in the pathogen Pseudomonas aeruginosa. Changes in their DNA binding regions, i.e., palindromic operators, can compromise pump depression and subsequently enhance resistance against several antibacterials and biocides. Here, we have identified (pseudo)palindromic repeats close to promoters of genes encoding 13 core drug-efflux pumps of P. aeruginosa. This framework was applied to detect mutations in these repeats in 17,292 genomes. Eighty-nine percent of isolates carried at least one mutation. Eight binary genetic properties potentially related to expression were calculated for mutations. These included palindromicity reduction, mutation type, positioning within the repeat and DNA-bending shift. High-risk ST298, ST308 and ST357 clones commonly carried four conserved mutations while ST175 and the cystic fibrosis-linked ST649 clones showed none. Remarkably, a T-to-C transition in the fourth position of the upstream repeat for mexEF-oprN was nearly exclusive of the high-risk ST111 clone. Other mutations were associated with high-risk sublineages using sample geotemporal metadata. Moreover, 1.5% of isolates carried five or more mutations suggesting they undergo an alternative program for regulation of their effluxome. Overall, P. aeruginosa shows a wide range of operator mutations with a potential effect on efflux pump expression and antibiotic resistance. Full article
(This article belongs to the Special Issue Mechanisms of Antimicrobial Resistance in Bacterial Pathogens)
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19 pages, 1019 KB  
Review
Efflux, Signaling and Warfare in a Polymicrobial World
by Ay’sha Moore-Machacek, Antje Gloe, Niall O’Leary and F. Jerry Reen
Antibiotics 2023, 12(4), 731; https://doi.org/10.3390/antibiotics12040731 - 8 Apr 2023
Cited by 7 | Viewed by 3470
Abstract
The discovery void of antimicrobial development has occurred at a time when the world has seen a rapid emergence and spread of antimicrobial resistance, the ‘perfect storm’ as it has often been described. While the discovery and development of new antibiotics has continued [...] Read more.
The discovery void of antimicrobial development has occurred at a time when the world has seen a rapid emergence and spread of antimicrobial resistance, the ‘perfect storm’ as it has often been described. While the discovery and development of new antibiotics has continued in the research sphere, the pipeline to clinic has largely been fed by derivatives of existing classes of antibiotics, each prone to pre-existing resistance mechanisms. A novel approach to infection management has come from the ecological perspective whereby microbial networks and evolved communities already possess small molecular capabilities for pathogen control. The spatiotemporal nature of microbial interactions is such that mutualism and parasitism are often two ends of the same stick. Small molecule efflux inhibitors can directly target antibiotic efflux, a primary resistance mechanism adopted by many species of bacteria and fungi. However, a much broader anti-infective capability resides within the action of these inhibitors, borne from the role of efflux in key physiological and virulence processes, including biofilm formation, toxin efflux, and stress management. Understanding how these behaviors manifest within complex polymicrobial communities is key to unlocking the full potential of the advanced repertoires of efflux inhibitors. Full article
(This article belongs to the Special Issue Efflux Pumps in Bacteria: What They Do and How We Can Stop Them)
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