The genetic basis of the fitness costs of antimicrobial resistance: a meta‐analysis approach

Vogwill, Tom; MacLean, R. Craig

doi:10.1111/eva.12202

Cited by 332 publications

(380 citation statements)

References 79 publications

(156 reference statements)

Supporting

Mentioning

331

Contrasting

Unclassified

Order By: Relevance

“…These range from in vitro systems, such as Biolog plates, that provide a variety of carbon sources (121,122), through more-complex synthetic systems or ex vivo animal models (123,124), all the way to in vivo analysis in nematodes (e.g., Caenorhabditis elegans [125]), insects (e.g., Galleria mellonella [126]), and mice or pigs (127,128). Nevertheless, despite the evident differences between laboratory culture medium and the natural bacterial habitat, the overall fitness effects of plasmids measured in vitro correlate quite well with their effects measured in mouse models (11).…”

Section: Expanding the Experimental Conditionsmentioning

confidence: 98%

“…Infection by a plasmid usually entails a fitness cost that reduces the reproductive rate of the host bacterium (11). This fitness cost plays a key role in the population biology of plasmids by generating selection against plasmid-carrying strains.…”

Section: Dissecting the Fitness Costs Produced By Plasmidsmentioning

confidence: 99%

“…It is therefore widely accepted that the main fitness cost associated with plasmids comes not from replication but from downstream events such as expression of plasmid genes (10,11). There is, nevertheless, evidence indicating that plasmid replication does incur a fitness cost for the bacterial host.…”

Section: Plasmid Replicationmentioning

confidence: 99%

“…In a recent meta-analysis, Vogwill and MacLean analyzed available data on the fitness effects of 49 plasmids examined in 16 studies (11). Remarkably, these authors found that the same plasmid generally has a very different fitness cost in different hosts, and that the variation coefficient for fitness effects of a single plasmid in different hosts does not differ significantly from that for the fitness effects of different plasmids in the same host (11). These results highlight the impossibility of using the fitness cost of a plasmid measured in one bacterial host to predict the effects of the same plasmid in other bacterial clones.…”

Section: High-throughput Approachesmentioning

confidence: 99%

“…Despite the potential benefits conferred by plasmids, they also produce a burden (fitness cost) in the host, manifesting as a reduced growth rate and weakened competitiveness of plasmid-bearing strains under conditions that do not select for plasmid-encoded genes (10,11). This fitness cost imposed by plasmids, coupled with the potential plasmid loss during bacterial cell division, hinders the survival of plasmids in bacterial communities.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Fitness Costs of Plasmids: a Limit to Plasmid Transmission

2017

Self Cite

View full text Add to dashboard Cite

Plasmids mediate the horizontal transmission of genetic information between bacteria, facilitating their adaptation to multiple environmental conditions. An especially important example of the ability of plasmids to catalyze bacterial adaptation and evolution is their instrumental role in the global spread of antibiotic resistance, which constitutes a major threat to public health. Plasmids provide bacteria with new adaptive tools, but they also entail a metabolic burden that, in the absence of selection for plasmid-encoded traits, reduces the competitiveness of the plasmid-carrying clone. Although this fitness reduction can be alleviated over time through compensatory evolution, the initial cost associated with plasmid carriage is the main constraint on the vertical and horizontal replication of these genetic elements. The fitness effects of plasmids therefore have a crucial influence on their ability to associate with new bacterial hosts and consequently on the evolution of plasmid-mediated antibiotic resistance. However, the molecular mechanisms underlying plasmid fitness cost remain poorly understood. Here, we analyze the literature in the field and examine the potential fitness effects produced by plasmids throughout their life cycle in the host bacterium. We also explore the various mechanisms evolved by plasmids and bacteria to minimize the cost entailed by these mobile genetic elements. Finally, we discuss potential future research directions in the field.

show abstract

Section: Expanding the Experimental Conditionsmentioning

confidence: 98%

Section: Dissecting the Fitness Costs Produced By Plasmidsmentioning

confidence: 99%

Section: Plasmid Replicationmentioning

confidence: 99%

Section: High-throughput Approachesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Fitness Costs of Plasmids: a Limit to Plasmid Transmission

2017

Self Cite

View full text Add to dashboard Cite

show abstract

Conjugation of Virulence Plasmid in Clinical Klebsiella pneumoniae Strains through Formation of a Fusion Plasmid

Xie

Chen

et al. 2020

Adv. Biosys.

View full text Add to dashboard Cite

The rapid dissemination of non‐conjugative virulence plasmids among non‐K1/K2 types of Klebsiella pneumoniae poses an unprecedented threat to human health, yet the underlying mechanisms governing dissemination of such plasmids is unclear. In this study, a novel 68 581 bp IncFIA plasmid is discovered that can be fused to a hypervirulence‐encoding plasmid to form a hybrid conjugative virulence plasmid in conjugation experiments; such fusion events involve homologous recombination between a 241 bp homologous region located in each of the two plasmids. The fusion hypervirulence‐encoding plasmid can be conjugated to both classic and blaKPC‐2‐bearing carbapenem‐resistant K. pneumoniae strains through conjugation, enabling such strains to acquire the ability to express the hypervirulence phenotype. Dissemination of this fusion virulence plasmid will impose an enormous burden on current efforts to control and treat infections caused by multidrug resistant and hypervirulent K. pneumoniae.

show abstract

Segregational instability of multicopy plasmids: A population genetics approach

Hernandez‐Beltran

Pina

Siri‐Jégousse

et al. 2022

Ecology and Evolution

View full text Add to dashboard Cite

Plasmids are extra‐chromosomal genetic elements that encode a wide variety of phenotypes and can be maintained in bacterial populations through vertical and horizontal transmission, thus increasing bacterial adaptation to hostile environmental conditions like those imposed by antimicrobial substances. To circumvent the segregational instability resulting from randomly distributing plasmids between daughter cells upon division, nontransmissible plasmids tend to be carried in multiple copies per cell, with the added benefit of exhibiting increased gene dosage and resistance levels. But carrying multiple copies also results in a high metabolic burden to the bacterial host, therefore reducing the overall fitness of the population. This trade‐off poses an existential question for plasmids: What is the optimal plasmid copy number? In this manuscript, we address this question by postulating and analyzing a population genetics model to evaluate the interaction between selective pressure, the number of plasmid copies carried by each cell, and the metabolic burden associated with plasmid bearing in the absence of selection for plasmid‐encoded traits. Parameter values of the model were estimated experimentally using Escherichia coli K12 carrying a multicopy plasmid encoding for a fluorescent protein and bla TEM‐1 , a gene conferring resistance to β ‐lactam antibiotics. By numerically determining the optimal plasmid copy number for constant and fluctuating selection regimes, we show that plasmid copy number is a highly optimized evolutionary trait that depends on the rate of environmental fluctuation and balances the benefit between increased stability in the absence of selection with the burden associated with carrying multiple copies of the plasmid.

show abstract

The genetic basis of the fitness costs of antimicrobial resistance: a meta‐analysis approach

Cited by 332 publications

References 79 publications

Fitness Costs of Plasmids: a Limit to Plasmid Transmission

Fitness Costs of Plasmids: a Limit to Plasmid Transmission

Conjugation of Virulence Plasmid in Clinical Klebsiella pneumoniae Strains through Formation of a Fusion Plasmid

Segregational instability of multicopy plasmids: A population genetics approach

Contact Info

Product

Resources

About