scholarly journals Resistance/fitness trade-off is a barrier to the evolution of MarR inactivation mutants in Escherichia coli

2020 ◽  
Vol 76 (1) ◽  
pp. 77-83 ◽  
Author(s):  
Lisa Praski Alzrigat ◽  
Douglas L Huseby ◽  
Gerrit Brandis ◽  
Diarmaid Hughes
Keyword(s):  
Escherichia Coli ◽  
Experimental Evolution ◽  
Efflux Pump ◽  
Drug Susceptibility ◽  
Fitness Cost ◽  
Competitive Growth ◽  
Contributing Factors ◽  
Trade Off ◽  
Compensatory Evolution ◽  
The Cost

Abstract Background Mutations that inactivate MarR reduce susceptibility to ciprofloxacin and competitive growth fitness in Escherichia coli. Both phenotypes are caused by overexpression of the MarA regulon, which includes the AcrAB-TolC drug efflux pump. Objectives We asked whether compensatory evolution could reduce the fitness cost of MarR-inactivating mutations without affecting resistance to ciprofloxacin. Methods The cost of overexpressing the AcrAB-TolC efflux pump was measured independently of MarA overexpression. Experimental evolution of MarR-inactive strains was used to select mutants with increased fitness. The acquired mutations were identified and their effects on drug susceptibility were measured. Results Overexpression of the AcrAB-TolC efflux pump was found not to contribute to the fitness cost of MarA regulon overexpression. Fitness-compensatory mutations were selected in marA and lon. The mutations reduced the level of MarA protein thus reducing expression of the MarA regulon. They restored growth fitness but also reduced resistance to ciprofloxacin. Conclusions The fitness cost caused by overexpression of the MarA regulon has multiple contributing factors. Experimental evolution did not identify any single pump-independent cost factor. Instead, efficient fitness compensation occurred only by mechanisms that reduce MarA concentration, which simultaneously reduce the drug resistance phenotype. This resistance/fitness trade-off is a barrier to the successful spread of MarR inactivation mutations in clinical isolates where growth fitness is essential.

scholarly journals Compensatory mutations modulate the competitiveness and dynamics of plasmid-mediated colistin resistance in Escherichia coli clones

2020 ◽  
Vol 14 (3) ◽  
pp. 861-865 ◽  
Author(s):  
Qiu E. Yang ◽  
Craig MacLean ◽  
Andrei Papkou ◽  
Manon Pritchard ◽  
Lydia Powell ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Fitness Landscape ◽  
Fitness Cost ◽  
Colistin Resistance ◽  
Bacterial Populations ◽  
Compensatory Evolution ◽  
Neutral Mutations ◽  
The Cost ◽  
Negative Epistasis

AbstractThe emergence of mobile colistin resistance (mcr) threatens to undermine the clinical efficacy of the last antibiotic that can be used to treat serious infections caused by Gram-negative pathogens. Here we measure the fitness cost of a newly discovered MCR-3 using in vitro growth and competition assays. mcr-3 expression confers a lower fitness cost than mcr-1, as determined by competitive ability and cell viability. Consistent with these findings, plasmids carrying mcr-3 have higher stability than mcr-1 plasmids across a range of Escherichia coli strains. Crucially, mcr-3 plasmids can stably persist, even in the absence of colistin. Recent compensatory evolution has helped to offset the cost of mcr-3 expression, as demonstrated by the high fitness of mcr-3.5 as opposed to mcr-3.1. Reconstructing all of the possible evolutionary trajectories from mcr-3.1 to mcr-3.5 reveals a complex fitness landscape shaped by negative epistasis between compensatory and neutral mutations. Our findings highlight the importance of fitness costs and compensatory evolution in driving the dynamics and stability of mobile colistin resistance in bacterial populations, and they highlight the need to understand how processes (other than colistin use) impact mcr dynamics.

scholarly journals Advantage of the F2:A1:B- IncF Pandemic Plasmid over IncC Plasmids in In Vitro Acquisition and Evolution of blaCTX-M Gene-Bearing Plasmids in Escherichia coli

2019 ◽  
Vol 63 (10) ◽  
Author(s):  
Anne-Claire Mahérault ◽  
Harry Kemble ◽  
Mélanie Magnan ◽  
Benoit Gachet ◽  
David Roche ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Experimental Evolution ◽  
Negative Impact ◽  
Fitness Cost ◽  
M Gene ◽  
Content Type ◽  
E Coli ◽  
Conjugative Plasmids ◽  
K 12

ABSTRACT Despite a fitness cost imposed on bacterial hosts, large conjugative plasmids play a key role in the diffusion of resistance determinants, such as CTX-M extended-spectrum β-lactamases. Among the large conjugative plasmids, IncF plasmids are the most predominant group, and an F2:A1:B- IncF-type plasmid encoding a CTX-M-15 variant was recently described as being strongly associated with the emerging worldwide Escherichia coli sequence type 131 (ST131)-O25b:H4 H30Rx/C2 sublineage. In this context, we investigated the fitness cost of narrow-range F-type plasmids, including the F2:A1:B- IncF-type CTX-M-15 plasmid, and of broad-range C-type plasmids in the K-12-like J53-2 E. coli strain. Although all plasmids imposed a significant fitness cost to the bacterial host immediately after conjugation, we show, using an experimental-evolution approach, that a negative impact on the fitness of the host strain was maintained throughout 1,120 generations with the IncC-IncR plasmid, regardless of the presence or absence of cefotaxime, in contrast to the F2:A1:B- IncF plasmid, whose cost was alleviated. Many chromosomal and plasmid rearrangements were detected after conjugation in transconjugants carrying the IncC plasmids but not in transconjugants carrying the F2:A1:B- IncF plasmid, except for insertion sequence (IS) mobilization from the fliM gene leading to the restoration of motility of the recipient strains. Only a few mutations occurred on the chromosome of each transconjugant throughout the experimental-evolution assay. Our findings indicate that the F2:A1:B- IncF CTX-M-15 plasmid is well adapted to the E. coli strain studied, contrary to the IncC-IncR CTX-M-15 plasmid, and that such plasmid-host adaptation could participate in the evolutionary success of the CTX-M-15-producing pandemic E. coli ST131-O25b:H4 lineage.

scholarly journals Fitness Cost and Compensation Mechanism of Sulfonamide Resistance Genes (Sul1, Sul2, and Sul3) in Escherichia Coli

2021 ◽  
Author(s):  
Yuqiao Zhou ◽  
Jiehong Fang ◽  
Zaeim Davood ◽  
Daofeng Qu ◽  
Jianzhong Han
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Fitness Cost ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Compensation Mechanism ◽  
Compensatory Evolution ◽  
Differential Proteins ◽  
Sulfonamide Resistance ◽  
Sulfonamide Resistance Gene

Abstract Background: The fitness cost of antibiotic resistance is a crucial factor to determine the evolutionary success of resistant bacteria. Even if the selection pressure in the environment is eliminated, drug-resistant bacteria can still compensate for drug-resistant genes' fitness cost through some compensation mechanisms. The fitness cost and compensatory evolution of antibiotic resistance are an essential part of bacterial evolution.Result: Engineered bacteria with the same genetic background that carry sulfonamide resistance gene were generated to explore the fitness cost of sulfonamide resistance gene in Escherichia coli. There were significant differences in the protein expression of the two-component system pathway (fliZ, fliA, fliC and lrhA), folate biosynthesis pathway (sul1, sul2 and sul3), ABC transporter system (ugpC, rbsA and gsiA), and outer membrane pore protein OmpD through the comparative analysis of differential proteins compared to sensitive bacteria. Thus, we could speculate the possible fitness compensation mechanism. Finally, qRT-PCR was used to verify the functions of some differential proteins at the transcriptional level.Conclusions: The study of fitness cost assessment and compensatory evolution of bacterial resistance will help understand the development track of antibiotic resistance of bacterial pathogens and provide new ideas for solving antibiotic resistance issues.

scholarly journals The effect of spatial structure on adaptation in Escherichia coli

2007 ◽  
Vol 4 (1) ◽  
pp. 57-59 ◽  
Author(s):  
Lilia Perfeito ◽  
M. Inês Pereira ◽  
Paulo R.A Campos ◽  
Isabel Gordo
Keyword(s):  
Escherichia Coli ◽  
Spatial Structure ◽  
Experimental Evolution ◽  
Petri Dish ◽  
Mutation Rates ◽  
Wild Type ◽  
Clonal Interference ◽  
Genetic Studies ◽  
Significant Difference ◽  
The Cost

Populations of organisms are generally organized in a given spatial structure. However, the vast majority of population genetic studies are based on populations in which every individual competes globally. Here we use experimental evolution in Escherichia coli to directly test a recently made prediction that spatial structure slows down adaptation and that this cost increases with the mutation rate. This was studied by comparing populations of different mutation rates adapting to a liquid (unstructured) medium with populations that evolved in a Petri dish on solid (structured) medium. We find that mutators adapt faster to both environments and that adaptation is slower if there is spatial structure. We observed no significant difference in the cost of structure between mutator and wild-type populations, which suggests that clonal interference is intense in both genetic backgrounds.

scholarly journals Compensatory Evolution in Rifampin-Resistant Escherichia coli

Genetics ◽  
2000 ◽  
Vol 156 (4) ◽  
pp. 1471-1481 ◽  
Author(s):  
Mary G Reynolds
Keyword(s):  
Escherichia Coli ◽  
Parallel Evolution ◽  
Clinical Problem ◽  
Relative Fitness ◽  
Serial Transfer ◽  
Compensatory Evolution ◽  
Rifampin Resistance ◽  
Compensatory Mutations ◽  
High Level ◽  
The Cost

Abstract This study examines the intrinsic fitness burden associated with RNA polymerase (rpoB) mutations conferring rifampin resistance in Escherichia coli K12 (MG1655) and explores the nature of adaptation to the costs of resistance. Among 28 independent Rifr mutants, the per-generation fitness burden (in the absence of rifampin) ranged from 0 to 28%, with a median of 6.4%. We detected no relationship between the magnitude of the cost and the level of resistance. Adaptation to the costs of rif resistance was studied by following serial transfer cultures for several Rifr mutants both in the presence of rifampin and in the absence. For cultures evolved in the absence of rifampin, single clones isolated after 200 generations were more fit than their ancestor; we saw no association between increased fitness and changes in the level of rifampin resistance; and in all cases, increased fitness was due to compensatory mutations, rather than to reversion to drug sensitivity. However, in the parallel evolution experiments in the presence of rifampin, overall levels of resistance increased as did relative fitness—for all strains save one that had an initially high level of resistance. Among the evolved clones tested, five (of seven) demonstrated increased transcription efficiency (assessed using a semiquantitative RT-PCR protocol). The implications of these results for our understanding of adaptive molecular evolution and the increasing clinical problem of antibiotic resistance are discussed.

Developing Schedule With Linear Programming (Case Study: STTF II Project Komplek Sukamukti Banjaran)

2020 ◽  
Vol 4 (02) ◽  
pp. 34-45
Author(s):  
Naufal Dzikri Afifi ◽  
Ika Arum Puspita ◽  
Mohammad Deni Akbar
Keyword(s):  
Linear Programming ◽  
Objective Function ◽  
Project Scheduling ◽  
Time Limit ◽  
Minimum Time ◽  
Service Cost ◽  
Trade Off ◽  
Overtime Work ◽  
The Cost

Shift to The Front II Komplek Sukamukti Banjaran Project is one of the projects implemented by one of the companies engaged in telecommunications. In its implementation, each project including Shift to The Front II Komplek Sukamukti Banjaran has a time limit specified in the contract. Project scheduling is an important role in predicting both the cost and time in a project. Every project should be able to complete the project before or just in the time specified in the contract. Delay in a project can be anticipated by accelerating the duration of completion by using the crashing method with the application of linear programming. Linear programming will help iteration in the calculation of crashing because if linear programming not used, iteration will be repeated. The objective function in this scheduling is to minimize the cost. This study aims to find a trade-off between the costs and the minimum time expected to complete this project. The acceleration of the duration of this study was carried out using the addition of 4 hours of overtime work, 3 hours of overtime work, 2 hours of overtime work, and 1 hour of overtime work. The normal time for this project is 35 days with a service fee of Rp. 52,335,690. From the results of the crashing analysis, the alternative chosen is to add 1 hour of overtime to 34 days with a total service cost of Rp. 52,375,492. This acceleration will affect the entire project because there are 33 different locations worked on Shift to The Front II and if all these locations can be accelerated then the duration of completion of the entire project will be effective

scholarly journals Black Hole Algorithm for Sustainable Design of Counterfort Retaining Walls

2020 ◽  
Vol 12 (7) ◽  
pp. 2767 ◽  
Author(s):  
Víctor Yepes ◽  
José V. Martí ◽  
José García
Keyword(s):  
Black Hole ◽  
Sustainable Design ◽  
Retaining Walls ◽  
The Other ◽  
Trade Off ◽  
Construction Company ◽  
Geometric Variables ◽  
The Stability ◽  
The Cost ◽  
Black Hole Algorithm

The optimization of the cost and CO 2 emissions in earth-retaining walls is of relevance, since these structures are often used in civil engineering. The optimization of costs is essential for the competitiveness of the construction company, and the optimization of emissions is relevant in the environmental impact of construction. To address the optimization, black hole metaheuristics were used, along with a discretization mechanism based on min–max normalization. The stability of the algorithm was evaluated with respect to the solutions obtained; the steel and concrete values obtained in both optimizations were analyzed. Additionally, the geometric variables of the structure were compared. Finally, the results obtained were compared with another algorithm that solved the problem. The results show that there is a trade-off between the use of steel and concrete. The solutions that minimize CO 2 emissions prefer the use of concrete instead of those that optimize the cost. On the other hand, when comparing the geometric variables, it is seen that most remain similar in both optimizations except for the distance between buttresses. When comparing with another algorithm, the results show a good performance in optimization using the black hole algorithm.

Sign in / Sign up

Export Citation Format

Share Document