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Antibiotic resistance is ancient

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TLDR
Target metagenomic analyses of rigorously authenticated ancient DNA from 30,000-year-old Beringian permafrost sediments are reported and show conclusively that antibiotic resistance is a natural phenomenon that predates the modern selective pressure of clinical antibiotic use.
Abstract
The discovery of antibiotics more than 70 years ago initiated a period of drug innovation and implementation in human and animal health and agriculture. These discoveries were tempered in all cases by the emergence of resistant microbes. This history has been interpreted to mean that antibiotic resistance in pathogenic bacteria is a modern phenomenon; this view is reinforced by the fact that collections of microbes that predate the antibiotic era are highly susceptible to antibiotics. Here we report targeted metagenomic analyses of rigorously authenticated ancient DNA from 30,000-year-old Beringian permafrost sediments and the identification of a highly diverse collection of genes encoding resistance to β-lactam, tetracycline and glycopeptide antibiotics. Structure and function studies on the complete vancomycin resistance element VanA confirmed its similarity to modern variants. These results show conclusively that antibiotic resistance is a natural phenomenon that predates the modern selective pressure of clinical antibiotic use.

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Journal ArticleDOI

Molecular mechanisms of antibiotic resistance.

TL;DR: Recent advances in understanding of the mechanisms by which bacteria are either intrinsically resistant or acquire resistance to antibiotics are reviewed, including the prevention of access to drug targets, changes in the structure and protection of antibiotic targets and the direct modification or inactivation of antibiotics.
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Natural Antibiotic Resistance and Contamination by Antibiotic Resistance Determinants: The Two Ages in the Evolution of Resistance to Antimicrobials

TL;DR: The study of antibiotic resistance has been historically concentrated on the analysis of bacterial pathogens and on the consequences of acquiring resistance for human health, but the studies on antibiotic resistance should not be confined to clinical-associated ecosystems.
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Antibacterial drug discovery in the resistance era

TL;DR: The looming antibiotic-resistance crisis has penetrated the consciousness of clinicians, researchers, policymakers, politicians and the public at large as discussed by the authors, and the evolution and widespread distribution of antibiotic-resistant elements in bacterial pathogens has made diseases that were once easily treatable deadly again.
Journal ArticleDOI

Antibiotics and Bacterial Resistance in the 21st Century

TL;DR: In this review the factors that have been linked to the waxing of bacterial resistance are addressed and profiles of bacterial species that are deemed to be particularly concerning at the present time are illustrated.
References
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Journal ArticleDOI

Improved tools for biological sequence comparison.

TL;DR: Three computer programs for comparisons of protein and DNA sequences can be used to search sequence data bases, evaluate similarity scores, and identify periodic structures based on local sequence similarity.
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Sampling the Antibiotic Resistome

TL;DR: This work has shown that soil-dwelling bacteria are a reservoir of resistance determinants that can be mobilized into the microbial community, and study of this reservoir could provide an early warning system for future clinically relevant antibiotic resistance mechanisms.
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The antibiotic resistome: the nexus of chemical and genetic diversity

TL;DR: Understanding the molecular diversity that underlies resistance will inform the use of these drugs and guide efforts to develop new efficacious antibiotics.
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Vancomycin resistance in gram-positive cocci.

TL;DR: The mode of action and the mechanism of bacterial resistance to glycopeptides, as exemplified by the VanA type, which is mediated by transposon Tn1546 and is widely spread in enterococci are reviewed.
Journal ArticleDOI

Functional Characterization of the Antibiotic Resistance Reservoir in the Human Microflora

TL;DR: To understand the process by which antibiotic resistance genes are acquired by human pathogens, functionally characterized the resistance reservoir in the microbial flora of healthy individuals and identified most of the resistance genes, which have not been previously identified and are evolutionarily distant from known resistance genes.
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