Faculty Opinions recommendation of Analysing the fitness cost of antibiotic resistance to identify targets for combination antimicrobials.

2021 ◽  
Author(s):  
Craig MacLean ◽  
Qin Qi
Keyword(s):  
Antibiotic Resistance ◽  
Fitness Cost

scholarly journals Increased Survival of Antibiotic-Resistant Escherichia coli inside Macrophages

2012 ◽  
Vol 57 (1) ◽  
pp. 189-195 ◽  
Author(s):  
Migla Miskinyte ◽  
Isabel Gordo
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Bacterial Infections ◽  
Resistance Mutation ◽  
Fitness Cost ◽  
Resistance Mutations ◽  
Content Type ◽  
E Coli ◽  
Fitness Effects ◽  
K 12

ABSTRACTMutations causing antibiotic resistance usually incur a fitness cost in the absence of antibiotics. The magnitude of such costs is known to vary with the environment. Little is known about the fitness effects of antibiotic resistance mutations when bacteria confront the host's immune system. Here, we study the fitness effects of mutations in therpoB,rpsL, andgyrAgenes, which confer resistance to rifampin, streptomycin, and nalidixic acid, respectively. These antibiotics are frequently used in the treatment of bacterial infections. We measured two important fitness traits—growth rate and survival ability—of 12Escherichia coliK-12 strains, each carrying a single resistance mutation, in the presence of macrophages. Strikingly, we found that 67% of the mutants survived better than the susceptible bacteria in the intracellular niche of the phagocytic cells. In particular, allE. colistreptomycin-resistant mutants exhibited an intracellular advantage. On the other hand, 42% of the mutants incurred a high fitness cost when the bacteria were allowed to divide outside of macrophages. This study shows that single nonsynonymous changes affecting fundamental processes in the cell can contribute to prolonged survival ofE. coliin the context of an infection.

scholarly journals Persistence of Transferable Extended-Spectrum-β-Lactamase Resistance in the Absence of Antibiotic Pressure

2012 ◽  
Vol 56 (9) ◽  
pp. 4703-4706 ◽  
Author(s):  
Jennifer L. Cottell ◽  
Mark A. Webber ◽  
Laura J. V. Piddock
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Gene ◽  
Resistance Genes ◽  
Antibiotic Resistance Genes ◽  
Fitness Cost ◽  
Resistant Bacteria ◽  
Bacterial Host ◽  
Antibiotic Resistant ◽  
M 14 ◽  
Host Strains

ABSTRACTThe treatment of infections caused by antibiotic-resistant bacteria is one of the great challenges faced by clinicians in the 21st century. Antibiotic resistance genes are often transferred between bacteria by mobile genetic vectors called plasmids. It is commonly believed that removal of antibiotic pressure will reduce the numbers of antibiotic-resistant bacteria due to the perception that carriage of resistance imposes a fitness cost on the bacterium. This study investigated the ability of the plasmid pCT, a globally distributed plasmid that carries an extended-spectrum-β-lactamase (ESBL) resistance gene (blaCTX-M-14), to persist and disseminate in the absence of antibiotic pressure. We investigated key attributes in plasmid success, including conjugation frequencies, bacterial-host growth rates, ability to cause infection, and impact on the fitness of host strains. We also determined the contribution of theblaCTX-M-14gene itself to the biology of the plasmid and host bacterium. Carriage of pCT was found to impose no detectable fitness cost on various bacterial hosts. An absence of antibiotic pressure and inactivation of the antibiotic resistance gene also had no effect on plasmid persistence, conjugation frequency, or bacterial-host biology. In conclusion, plasmids such as pCT have evolved to impose little impact on host strains. Therefore, the persistence of antibiotic resistance genes and their vectors is to be expected in the absence of antibiotic selective pressure regardless of antibiotic stewardship. Other means to reduce plasmid stability are needed to prevent the persistence of these vectors and the antibiotic resistance genes they carry.

Phenotypic changes associated with the fitness cost in antibiotic resistant Escherichia coli strains

2016 ◽  
Vol 12 (2) ◽  
pp. 414-420 ◽  
Author(s):  
Shingo Suzuki ◽  
Takaaki Horinouchi ◽  
Chikara Furusawa
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Fitness Cost ◽  
Bacterial Cells ◽  
Antibiotic Resistant ◽  
Phenotypic Changes

Background: the acquisition of antibiotic resistance in bacterial cells is often accompanied with a reduction of fitness in the absence of antibiotics, known as the “fitness cost”.

scholarly journals Reversing Antibiotic Resistance Caused by Mobile Resistance Genes of High Fitness Cost

mSphere ◽  
2021 ◽  
Author(s):  
Jinyong Wu ◽  
Xiaohong Dong ◽  
Lihua Zhang ◽  
Yufei Lin ◽  
Kun Yang
Keyword(s):  
Antibiotic Resistance ◽  
Human Health ◽  
Resistance Genes ◽  
Fitness Cost ◽  
Bacterial Antibiotic Resistance ◽  
High Fitness ◽  
New Antibiotics

The dissemination of bacterial antibiotic resistance is a serious threat to human health. The development of new antibiotics faces both economic and technological challenges.

scholarly journals Resistance diagnostics as a public health tool to combat antibiotic resistance: A model-based evaluation

2018 ◽  
Author(s):  
David McAdams ◽  
Kristofer Wollein Waldetoft ◽  
Christine Tedijanto ◽  
Marc Lipsitch ◽  
Sam P. Brown
Keyword(s):  
Public Health ◽  
Antibiotic Resistance ◽  
Point Of Care ◽  
Fitness Cost ◽  
Opportunistic Pathogens ◽  
Targeted Interventions ◽  
Drug Choice ◽  
Informed Treatment ◽  
Resistant Strains ◽  
Improve Treatment Efficacy

AbstractRapid point-of-care resistance diagnostics (POC-RD) are a key tool in the fight against antibiotic resistance. By tailoring drug choice to infection genotype, doctors can improve treatment efficacy while limiting costs of inappropriate antibiotic prescription. Here we combine epidemiological theory and data to assess the potential of RD innovations in a public health context, as a means to limit or even reverse selection for antibiotic resistance. POC-RD can be used to impose a non-biological fitness cost on resistant strains, by enabling diagnostic-informed treatment and targeted interventions that reduce resistant strains’ opportunities for transmission. We assess this diagnostic-imposed fitness cost in the context of a spectrum of bacterial population biologies, and find that the expected impact varies from selection against resistance for obligate pathogens to marginal public health improvements for opportunistic pathogens with high ‘bystander’ antibiotic exposure during asymptomatic carriage (e.g. the pneumococcus). We close by generalizing the notion of RD-informed strategies to incorporate carriage surveillance information, and illustrate that coupling transmission-control interventions to the discovery of resistant strains in carriage can potentially select against resistance in a broad range of opportunistic pathogens.

scholarly journals PixR, a Novel Activator of Conjugative Transfer of IncX4 Resistance Plasmids, Mitigates the Fitness Cost of mcr-1 Carriage in Escherichia coli

mBio ◽  
2022 ◽  
Author(s):  
Lingxian Yi ◽  
Romain Durand ◽  
Frédéric Grenier ◽  
Jun Yang ◽  
Kaiyang Yu ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Molecular Mechanisms ◽  
Antibiotic Resistance Genes ◽  
Fitness Cost ◽  
Conjugative Transfer ◽  
Resistance Plasmids

The spread of clinically relevant antibiotic resistance genes is often linked to the dissemination of epidemic plasmids. However, the underlying molecular mechanisms contributing to the successful spread of epidemic plasmids remain unclear.

Reduction of the fitness cost of antibiotic resistance caused by chromosomal mutations under poor nutrient conditions

2018 ◽  
Vol 120 ◽  
pp. 63-71 ◽  
Author(s):  
Wenfang Lin ◽  
Jie Zeng ◽  
Kun Wan ◽  
Lu Lv ◽  
Lizheng Guo ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Fitness Cost ◽  
Chromosomal Mutations ◽  
Nutrient Conditions

scholarly journals The genomic basis of adaptation to the fitness cost of rifampicin resistance in Pseudomonas aeruginosa

2016 ◽  
Vol 283 (1822) ◽  
pp. 20152452 ◽  
Author(s):  
Qin Qi ◽  
Macarena Toll-Riera ◽  
Karl Heilbron ◽  
Gail M. Preston ◽  
R. Craig MacLean
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Low Cost ◽  
Fitness Cost ◽  
Clinical Settings ◽  
Resistance Mutations ◽  
Beneficial Mutations ◽  
Cost Of Resistance ◽  
Compensatory Mutations ◽  
The Cost

Antibiotic resistance carries a fitness cost that must be overcome in order for resistance to persist over the long term. Compensatory mutations that recover the functional defects associated with resistance mutations have been argued to play a key role in overcoming the cost of resistance, but compensatory mutations are expected to be rare relative to generally beneficial mutations that increase fitness, irrespective of antibiotic resistance. Given this asymmetry, population genetics theory predicts that populations should adapt by compensatory mutations when the cost of resistance is large, whereas generally beneficial mutations should drive adaptation when the cost of resistance is small. We tested this prediction by determining the genomic mechanisms underpinning adaptation to antibiotic-free conditions in populations of the pathogenic bacterium Pseudomonas aeruginosa that carry costly antibiotic resistance mutations. Whole-genome sequencing revealed that populations founded by high-cost rifampicin-resistant mutants adapted via compensatory mutations in three genes of the RNA polymerase core enzyme, whereas populations founded by low-cost mutants adapted by generally beneficial mutations, predominantly in the quorum-sensing transcriptional regulator gene lasR . Even though the importance of compensatory evolution in maintaining resistance has been widely recognized, our study shows that the roles of general adaptation in maintaining resistance should not be underestimated and highlights the need to understand how selection at other sites in the genome influences the dynamics of resistance alleles in clinical settings.

scholarly journals Salicylate Increases Fitness Cost Associated with MarA-Mediated Antibiotic Resistance

2019 ◽  
Vol 117 (3) ◽  
pp. 563-571 ◽  
Author(s):  
Tiebin Wang ◽  
Colin Kunze ◽  
Mary J. Dunlop
Keyword(s):  
Antibiotic Resistance ◽  
Fitness Cost
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