Within-patient evolution of plasmid-mediated antimicrobial resistance
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TLDR
In this paper , the plasmid pOXA-48 was tracked in a large collection of enterobacterial clones isolated from the gut of hospitalised patients, and the authors observed that the evolution of plasmID-mediated AMR in vivo involves a pivotal trade-off between resistance levels and bacterial fitness.Abstract:
Abstract Antibiotic resistance (AMR) in bacteria is a major threat to public health, and one of the key elements in the spread and evolution of AMR in clinical pathogens is the transfer of conjugative plasmids. The drivers of AMR evolution have been extensively studied in vitro , but the evolution of plasmid-mediated AMR in vivo remains poorly explored. Here, we tracked the evolution of the clinically-relevant plasmid pOXA-48, which confers resistance to the last-resort antibiotics carbapenems, in a large collection of enterobacterial clones isolated from the gut of hospitalised patients. Combining genomic and experimental approaches, we first characterized plasmid diversity and the genotypic and phenotypic effects of multiple plasmid mutations on a common genetic background. Second, using cutting-edge genomic editing in wild-type multidrug resistant enterobacteria, we dissected three cases of within-patient plasmid-mediated AMR evolution. Our results revealed, for the first time, compensatory evolution of plasmid-associated fitness cost, as well as the evolution of enhanced plasmid-mediated AMR, in bacteria evolving within the gut of hospitalised patients. Crucially, we observed that the evolution of plasmid-mediated AMR in vivo involves a pivotal trade-off between resistance levels and bacterial fitness. This study highlights the need to develop new evolution-informed approaches to tackle plasmid-mediated AMR dissemination. read more
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Diverse and abundant viruses exploit conjugative plasmids
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TL;DR: In this paper , the authors systematically search for new plasmid-dependent phages using a targeted discovery platform, and find that they are in fact common and abundant in nature, and vastly unexplored in terms of their genetic diversity.
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Evolutionary responses to acquiring a multidrug resistance plasmid are dominated by metabolic functions across diverse <i>Escherichia coli</i> lineages
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TL;DR: In this paper , the authors show that plasmid fitness cost could be ameliorated by compensatory mutations affecting the chromosomal global regulatory system gacA/gacS , which arose rapidly in plant rhizosphere communities.
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