Bad Bugs in the XXIst Century: Resistance Mediated by Multi-Drug Efflux Pumps in Gram-Negative Bacteria

The discovery of antibiotics represented a key milestone in the history of medicine. However, with the rise of these life-saving drugs came the awareness that bacteria deploy defence mechanisms to resist these antibiotics, and they are good at it. Today, we appear at a crossroads between discovery o...

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Autores principales: Hiroshi Nikaido, Attilio Vittorio Vargiu, Klaas Martinus Pos, Keith Poole
Formato: Online
Lenguaje:inglés
Publicado: Frontiers Media SA 2021
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Acceso en línea:18318
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author Hiroshi Nikaido
Attilio Vittorio Vargiu
Klaas Martinus Pos
Keith Poole
author_browse Attilio Vittorio Vargiu
Hiroshi Nikaido
Keith Poole
Klaas Martinus Pos
author_facet Hiroshi Nikaido
Attilio Vittorio Vargiu
Klaas Martinus Pos
Keith Poole
author_sort Hiroshi Nikaido
collection Directory of Open Access Books
description The discovery of antibiotics represented a key milestone in the history of medicine. However, with the rise of these life-saving drugs came the awareness that bacteria deploy defence mechanisms to resist these antibiotics, and they are good at it. Today, we appear at a crossroads between discovery of new potent drugs and omni-resistant superbugs. Moreover, the misuse of antibiotics in different industries has increased the rate of resistance development by providing permanent selective pressure and, subsequently, enrichment of multidrug resistant pathogens. As a result, antimicrobial resistance has now become an urgent threat to public health worldwide (http://www.who.int/drugresistance/documents/surveillancereport/en/). The development of multidrug resistance (MDR) in an increasing number of pathogens, including Pseudomonas, Acinetobacter, Klebsiella, Salmonella, Burkholderia, and other Gram-negative bacteria is a most severe issue. Membrane efflux pump complexes of the Resistance-Nodulation-cell Division (RND) superfamily play a key role in the development of MDR in these bacteria. RND pumps, together with other transporters, contribute to intrinsic and acquired resistance to most, if not all, of the antimicrobial compounds available in our drug arsenal. Given the enormous drug polyspecificity of MDR efflux pumps, studies on their mechanism of action are extremely challenging, and this has negatively impacted both the development of new antibiotics that are able to evade these efflux pumps as well as the design of pump inhibitors. The collection of articles in this eBook, published as a Research Topic in Frontiers in Microbiology, section of Antimicrobials, Resistance, and Chemotherapy, aims to update the reader about the latest advances on the structure and function of RND efflux transporters, their roles in the overall multidrug resistance phenotype of Gram-negative pathogens, and on strategies to inhibit their activities. A deeper understanding of the mechanisms by which RND efflux pumps, alone or synergistically with other efflux pumps, are able to limit the concentration of antimicrobial compounds inside the bacterial cell, may pave the way for new, more directed, inhibitor and antibiotic design to ultimately overcome antimicrobial resistance by Gram-negatives.
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spelling doab-20.500.12854ir-417782024-04-05T17:31:06Z Bad Bugs in the XXIst Century: Resistance Mediated by Multi-Drug Efflux Pumps in Gram-Negative Bacteria Hiroshi Nikaido Attilio Vittorio Vargiu Klaas Martinus Pos Keith Poole QR1-502 Q1-390 Resistance-Nodulation Division transporters multi-drug-resistant pathogens antibiotic resistance Gram-Negative Bacteria bacterial resistance mechanisms Superbugs efflux pumps thema EDItEUR::P Mathematics and Science::PS Biology, life sciences::PSG Microbiology (non-medical) The discovery of antibiotics represented a key milestone in the history of medicine. However, with the rise of these life-saving drugs came the awareness that bacteria deploy defence mechanisms to resist these antibiotics, and they are good at it. Today, we appear at a crossroads between discovery of new potent drugs and omni-resistant superbugs. Moreover, the misuse of antibiotics in different industries has increased the rate of resistance development by providing permanent selective pressure and, subsequently, enrichment of multidrug resistant pathogens. As a result, antimicrobial resistance has now become an urgent threat to public health worldwide (http://www.who.int/drugresistance/documents/surveillancereport/en/). The development of multidrug resistance (MDR) in an increasing number of pathogens, including Pseudomonas, Acinetobacter, Klebsiella, Salmonella, Burkholderia, and other Gram-negative bacteria is a most severe issue. Membrane efflux pump complexes of the Resistance-Nodulation-cell Division (RND) superfamily play a key role in the development of MDR in these bacteria. RND pumps, together with other transporters, contribute to intrinsic and acquired resistance to most, if not all, of the antimicrobial compounds available in our drug arsenal. Given the enormous drug polyspecificity of MDR efflux pumps, studies on their mechanism of action are extremely challenging, and this has negatively impacted both the development of new antibiotics that are able to evade these efflux pumps as well as the design of pump inhibitors. The collection of articles in this eBook, published as a Research Topic in Frontiers in Microbiology, section of Antimicrobials, Resistance, and Chemotherapy, aims to update the reader about the latest advances on the structure and function of RND efflux transporters, their roles in the overall multidrug resistance phenotype of Gram-negative pathogens, and on strategies to inhibit their activities. A deeper understanding of the mechanisms by which RND efflux pumps, alone or synergistically with other efflux pumps, are able to limit the concentration of antimicrobial compounds inside the bacterial cell, may pave the way for new, more directed, inhibitor and antibiotic design to ultimately overcome antimicrobial resistance by Gram-negatives. 2021-02-11T08:50:10Z 2021-02-11T08:50:10Z 2016-01-19 14:05:46 2016 book 18318 16648714 9782889199310 https://directory.doabooks.org/handle/20.500.12854/41778 eng Frontiers Research Topics image/jpeg Attribution 4.0 International http://www.frontiersin.org/books/Bad_Bugs_in_the_XXIst_Century_Resistance_Mediated_by_Multi-Drug_Ffflux_Pumps_in_Gram-Negative_Bacte/960#nogo http://journal.frontiersin.org/researchtopic/2904/bad-bugs-in-the-xxist-century-resistance-mediated-by-multi-drug-efflux-pumps-in-gram-negative-bacter Frontiers Media SA 10.3389/978-2-88919-931-0 10.3389/978-2-88919-931-0 bf5ce210-e72e-4860-ba9b-c305640ff3ae 9782889199310 193 open access
spellingShingle QR1-502
Q1-390
Resistance-Nodulation Division transporters
multi-drug-resistant pathogens
antibiotic resistance
Gram-Negative Bacteria
bacterial resistance mechanisms
Superbugs
efflux pumps
thema EDItEUR::P Mathematics and Science::PS Biology, life sciences::PSG Microbiology (non-medical)
Hiroshi Nikaido
Attilio Vittorio Vargiu
Klaas Martinus Pos
Keith Poole
Bad Bugs in the XXIst Century: Resistance Mediated by Multi-Drug Efflux Pumps in Gram-Negative Bacteria
title Bad Bugs in the XXIst Century: Resistance Mediated by Multi-Drug Efflux Pumps in Gram-Negative Bacteria
title_full Bad Bugs in the XXIst Century: Resistance Mediated by Multi-Drug Efflux Pumps in Gram-Negative Bacteria
title_fullStr Bad Bugs in the XXIst Century: Resistance Mediated by Multi-Drug Efflux Pumps in Gram-Negative Bacteria
title_full_unstemmed Bad Bugs in the XXIst Century: Resistance Mediated by Multi-Drug Efflux Pumps in Gram-Negative Bacteria
title_short Bad Bugs in the XXIst Century: Resistance Mediated by Multi-Drug Efflux Pumps in Gram-Negative Bacteria
title_sort bad bugs in the xxist century resistance mediated by multi drug efflux pumps in gram negative bacteria
topic QR1-502
Q1-390
Resistance-Nodulation Division transporters
multi-drug-resistant pathogens
antibiotic resistance
Gram-Negative Bacteria
bacterial resistance mechanisms
Superbugs
efflux pumps
thema EDItEUR::P Mathematics and Science::PS Biology, life sciences::PSG Microbiology (non-medical)
topic_facet QR1-502
Q1-390
Resistance-Nodulation Division transporters
multi-drug-resistant pathogens
antibiotic resistance
Gram-Negative Bacteria
bacterial resistance mechanisms
Superbugs
efflux pumps
thema EDItEUR::P Mathematics and Science::PS Biology, life sciences::PSG Microbiology (non-medical)
url 18318
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