Pulling Together to Beat Superbugs Knowledge and Implementation Gaps in Addressing Antimicrobial Resistance

Berthe, Franck; Wadsworth, Jonathan; Thiebaud, Alessia; Marquez, Patricio V.; Barış, Enis

doi:10.1596/32552

Cited by 7 publications

(2 citation statements)

References 117 publications

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“…Antimicrobial resistance (AMR) is one of the greatest threats against human and animal health [1–4]. The ability to reliably identify resistance in bacterial isolates is essential for appropriate treatment as well as surveillance [1].…”

Section: Introductionmentioning

confidence: 99%

ResFinder – an open online resource for identification of antimicrobial resistance genes in next-generation sequencing data and prediction of phenotypes from genotypes

et al. 2022

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Antimicrobial resistance (AMR) is one of the most important health threats globally. The ability to accurately identify resistant bacterial isolates and the individual antimicrobial resistance genes (ARGs) is essential for understanding the evolution and emergence of AMR and to provide appropriate treatment. The rapid developments in next-generation sequencing technologies have made this technology available to researchers and microbiologists at routine laboratories around the world. However, tools available for those with limited experience with bioinformatics are lacking, especially to enable researchers and microbiologists in low- and middle-income countries (LMICs) to perform their own studies. The CGE-tools (Center for Genomic Epidemiology) including ResFinder (https://cge.cbs.dtu.dk/services/ResFinder/) was developed to provide freely available easy to use online bioinformatic tools allowing inexperienced researchers and microbiologists to perform simple bioinformatic analyses. The main purpose was and is to provide these solutions for people involved in frontline diagnosis especially in LMICs. Since its original publication in 2012, ResFinder has undergone a number of improvements including improvement of the code and databases, inclusion of point mutations for selected bacterial species and predictions of phenotypes also for selected species. As of 28 September 2021, 820 803 analyses have been performed using ResFinder from 61 776 IP-addresses in 171 countries. ResFinder clearly fulfills a need for several people around the globe and we hope to be able to continue to provide this service free of charge in the future. We also hope and expect to provide further improvements including phenotypic predictions for additional bacterial species.

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Section: Introductionmentioning

confidence: 99%

ResFinder – an open online resource for identification of antimicrobial resistance genes in next-generation sequencing data and prediction of phenotypes from genotypes

et al. 2022

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“…Over the past decades, the looming crisis of multidrug-resistant bacterial pathogens has become acute due to the shortage of novel antibiotics entering the market since the 1970s. Aside from few new classes like oxazolidines and lipopeptides, only derivatives of already existing compounds have been approved by the FDA (3,4). Classical targets of broad-spectrum antibiotics are essential processes like the bacterial cell wall or protein synthesis.…”

Section: Introductionmentioning

confidence: 99%

Same same but different – The global response ofEscherichia colito five different LpxC inhibitors

Möller,

Vázquez-Hernández,

Kutscher

et al. 2023

Preprint

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A promising but yet clinically unexploited antibiotic target in difficult-to-treat Gram-negative bacteria is LpxC, the key enzyme in the biosynthesis of lipopolysaccharides (LPS), which are the major constituents of the outer membrane. To gain insights into the mode of action of five different LpxC inhibitors, we conducted a comparative phenotypic and proteomic analysis. All five compounds bound to purified LpxC from Escherichia coli. Treatment of E. coli with these compounds changed the cell shape and stabilized LpxC suggesting that the FtsH-mediated turnover is impaired. LpxC inhibition sensitized E. coli to the cell wall antibiotic vancomycin, which typically does not cross the outer membrane. Four of the five compounds led to an accumulation of lyso-PE, a cleavage product of phosphatidylethanolamine (PE), generated by the phospholipase PldA. The combined results suggested an imbalance in phospholipid (PL) and LPS biosynthesis, which was corroborated by the global proteome response to treatment with the LpxC inhibitors. Apart from LpxC itself, FabA and FabB responsible for the biosynthesis of unsaturated fatty acids, were consistently upregulated. Our work also shows that antibiotics targeting the same enzyme do not necessarily elicit identical cellular responses. Compound-specific marker proteins belonged to different functional categories, like stress responses, nucleotide or amino acid metabolism and quorum sensing. These findings provide new insights into common and distinct cellular defense mechanisms against LpxC inhibition. Moreover, they support a delicate balance between LPS and PL biosynthesis with great potential as point of attack for antimicrobial intervention.

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Antimicrobial Resistance as a Creeping Crisis

Engström

2021

Understanding the Creeping Crisis

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Antimicrobial resistance (AMR) displays many of the characteristics of a creeping crisis. It lacks clearly definable temporal and spatial boundaries. It develops in the natural world when and where conditions are conducive. It traverses sectors and borders in the natural, human, and built environments. It causes individual and societal harm when it escalates toward outbreaks in a random fashion. Outbreaks can be minor or major, burn fast or slow, be simple or hard to contain. Experts insist we are heading toward a “post-antibiotic age” and even deadlier “superbugs” if we do not act. Yet warnings and crisis framings do not appear sufficient to prompt a response. Public attention and governmental action have lagged. Occasional outbreaks invite attention and concern, only for the issue to fade again from the public view. International organizations shine more sustained light on the problem, but national governments are slow to respond. This chapter argues that our dependency on antimicrobial drugs is a blessing and a curse: curing us in the short term but building the conditions for a massive, incurable outbreak in the future.

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Pulling Together to Beat Superbugs Knowledge and Implementation Gaps in Addressing Antimicrobial Resistance

Cited by 7 publications

References 117 publications

ResFinder – an open online resource for identification of antimicrobial resistance genes in next-generation sequencing data and prediction of phenotypes from genotypes

ResFinder – an open online resource for identification of antimicrobial resistance genes in next-generation sequencing data and prediction of phenotypes from genotypes

Same same but different – The global response ofEscherichia colito five different LpxC inhibitors

Antimicrobial Resistance as a Creeping Crisis

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