scholarly journals Selection for antibiotic resistance is reduced when embedded in a natural microbial community

2019 ◽  
Author(s):  
Uli Klümper ◽  
Mario Recker ◽  
Lihong Zhang ◽  
Xiaole Yin ◽  
Tong Zhang ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Microbial Community ◽  
Single Species ◽  
Natural Environments ◽  
Order Of Magnitude ◽  
Natural Microbial Community ◽  
Cost Of Resistance ◽  
Selection For ◽  
The Cost ◽  
Selection Of

AbstractAntibiotic resistance has emerged as one of the most pressing, global threats to public health. In single-species experiments selection for antibiotic resistance occurs at very low antibiotic concentrations. However, it is unclear how far these findings can be extrapolated to natural environments, where species are embedded within complex communities. We competed isogenic strains of Escherichia coli, differing exclusively in a single chromosomal resistance determinant, in the presence and absence of a pig fecal microbial community across a gradient of antibiotic concentration for two relevant antibiotics: gentamicin and kanamycin. We show that the minimal selective concentration was increased by more than one order of magnitude for both antibiotics when embedded in the community. We identified two general mechanisms were responsible for the increase in minimal selective concentration: an increase in the cost of resistance and a protective effect of the community for the susceptible phenotype. These findings have implications for our understanding of the evolution and selection of antibiotic resistance, and can inform future risk assessment efforts on antibiotic concentrations.

scholarly journals Selection for plasmid post–segregational killing depends on multiple infection: evidence for the selection of more virulent parasites through parasite–level competition

2005 ◽  
Vol 272 (1561) ◽  
pp. 403-410 ◽  
Author(s):  
T. F. Cooper ◽  
J. A. Heinemann
Keyword(s):  
Growth Rate ◽  
Growth Rates ◽  
Multiple Infection ◽  
Virulence Determinant ◽  
New Hosts ◽  
Parasite Reproduction ◽  
Selection For ◽  
The Cost ◽  
Selection Of

Is the virulence of parasites an outcome of optimized infection? Virulence has often been considered an inevitable consequence of parasite reproduction when the cost incurred by the parasite in reducing the fitness of its current host is offset by increased infection of new hosts. More recent models have focused on how competition occurring between parasites during co–infection might effect selection of virulence. For example, if co–infection was common, parasites with higher intrinsic growth rates might be selected, even at the expense of being optimally adapted to infect new hosts. If growth rate is positively correlated with virulence, then competition would select increased virulence. We tested these models using a plasmid–encoded virulence determinant. The virulence determinant did not contribute to the plasmid's reproduction within or between hosts. Despite this, virulent plasmids were more successful than avirulent derivatives during selection in an environment allowing within–host competition. To explain these findings we propose and test a model in which virulent parasites are selected by reducing the reproduction of competitors.

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 Selection for antimicrobial resistance is reduced when embedded in a natural microbial community

2019 ◽  
Vol 13 (12) ◽  
pp. 2927-2937 ◽  
Author(s):  
Uli Klümper ◽  
Mario Recker ◽  
Lihong Zhang ◽  
Xiaole Yin ◽  
Tong Zhang ◽  
...  
Keyword(s):  
Microbial Community ◽  
Antimicrobial Resistance ◽  
Natural Microbial Community ◽  
Selection For

scholarly journals DNA breaks-mediated cost reveals RNase HI as a new target for selectively eliminating antibiotic resistance

2019 ◽  
Author(s):  
Roberto Balbontín ◽  
Nelson Frazão ◽  
Isabel Gordo
Keyword(s):  
Antibiotic Resistance ◽  
Resistant Bacteria ◽  
Dna Breaks ◽  
Main Determinant ◽  
Gut Colonization ◽  
Antibiotics Use ◽  
Rnase Hi ◽  
Cost Of Resistance ◽  
The Cost ◽  
Drug Free

AbstractAntibiotic resistance often generates a fitness cost to bacteria in drug-free environments. Understanding the causes of the cost is considered the Holy Grail in the antibiotic resistance field, as it is the main determinant of the prevalence of resistances upon reducing antibiotics use. We show that DNA breaks can explain most of the variation in the cost of resistances common in pathogens. Here we demonstrate that targeting the RNase that degrades R-loops, which cause DNA breaks, exacerbates the cost of resistance. Consequently, lack of RNase HI function drives resistant clones to extinction in populations with high initial frequency of resistance, both in laboratory conditions and in a mouse model of gut colonization. Thus, RNase HI provides a target specific against resistant bacteria, which we validate using a repurposed drug. In summary, we revealed key mechanisms underlying the cost of antibiotic resistance that can be exploited to specifically eliminate resistant bacteria.

scholarly journals Novel Insights into Selection for Antibiotic Resistance in Complex Microbial Communities

mBio ◽  
2018 ◽  
Vol 9 (4) ◽  
Author(s):  
Aimee K. Murray ◽  
Lihong Zhang ◽  
Xiaole Yin ◽  
Tong Zhang ◽  
Angus Buckling ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Microbial Communities ◽  
Single Species ◽  
Dependent Manner ◽  
Antibiotic Concentration ◽  
Antibiotic Resistant ◽  
Global Issues ◽  
Clinical Environments ◽  
Selection For ◽  
Antibiotic Degradation

ABSTRACTRecent research has demonstrated that selection for antibiotic resistance occurs at very low antibiotic concentrations in single-species experiments, but the relevance of these findings when species are embedded in complex microbial communities is unclear. We show that the strength of selection for naturally occurring resistance alleles in a complex community remains constant from low subinhibitory to above clinically relevant concentrations. Selection increases with antibiotic concentration before reaching a plateau where selection remains constant over a 2-order-magnitude concentration range. This is likely to be due to cross protection of the susceptible bacteria in the community following rapid extracellular antibiotic degradation by the resistant population, shown experimentally through a combination of chemical quantification and bacterial growth experiments. Metagenome and 16S rRNA analyses of sewage-derived bacterial communities evolved under cefotaxime exposure show preferential enrichment forblaCTX-Mgenes over all other beta-lactamase genes, as well as positive selection and co-selection for antibiotic resistant, opportunistic pathogens. These findings have far-reaching implications for our understanding of the evolution of antibiotic resistance, by challenging the long-standing assumption that selection occurs in a dose-dependent manner.IMPORTANCEAntibiotic resistance is one of the greatest global issues facing society. Still, comparatively little is known about selection for resistance at very low antibiotic concentrations. We show that the strength of selection for clinically important resistance genes within a complex bacterial community can remain constant across a large antibiotic concentration range (wide selective space). Therefore, largely understudied ecological compartments could be just as important as clinical environments for selection of antibiotic resistance.

scholarly journals Effects of Sulfamethoxazole on Growth and Antibiotic Resistance of A Natural Microbial Community

Water ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1262
Author(s):  
Jasmin Rauseo ◽  
Anna Barra Caracciolo ◽  
Francesca Spataro ◽  
Andrea Visca ◽  
Nicoletta Ademollo ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Microbial Community ◽  
Antibiotic Resistance Gene ◽  
Antibiotic Resistance Genes ◽  
Antibiotic Resistant ◽  
Emerging Compounds ◽  
Mixed Microbial Community ◽  
Natural Microbial Community ◽  
Community Growth ◽  
Animal Exposure

Diffuse environmental antibiotic and antibiotic resistance gene contamination is increasing human and animal exposure to these emerging compounds with a consequent risk of reduction in antibiotic effectiveness. The present work investigated the effect of the antibiotic sulfamethoxazole (SMX) on growth and antibiotic resistance genes of a microbial community collected from an anaerobic digestion plant fed with cattle manure. Digestate samples were used as inoculum for concentration-dependent experiments using SMX at various concentrations. The antibiotic concentrations affecting the mixed microbial community in terms of growth and spread of resistant genes (sul1, sul2) were investigated through OD (Optical Density) measures and qPCR assays. Moreover, SMX biodegradation was assessed by LC-MS/MS analysis. The overall results showed that SMX concentrations in the range of those found in the environment did not affect the microbial community growth and did not select for antibiotic-resistant gene (ARG) maintenance or spread. Furthermore, the microorganisms tested were able to degrade SMX in only 24 h. This study confirms the complexity of antibiotic resistance spread in real matrices where different microorganisms coexist and suggests that antibiotic biodegradation needs to be included for fully understanding the resistance phenomena among bacteria.

scholarly journals Epistasis between antibiotic resistance mutations and genetic background shape the fitness effect of resistance across species of Pseudomonas

2016 ◽  
Vol 283 (1830) ◽  
pp. 20160151 ◽  
Author(s):  
T. Vogwill ◽  
M. Kojadinovic ◽  
R. C. MacLean
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Mutations ◽  
Bacterial Strains ◽  
Fitness Effect ◽  
Epistatic Interactions ◽  
Fitness Effects ◽  
Cost Of Resistance ◽  
Pathogen Populations ◽  
The Cost ◽  
Antibiotic Resistance Mutations

Antibiotic resistance often evolves by mutations at conserved sites in essential genes, resulting in parallel molecular evolution between divergent bacterial strains and species. Whether these resistance mutations are having parallel effects on fitness across bacterial taxa, however, is unclear. This is an important point to address, because the fitness effects of resistance mutations play a key role in the spread and maintenance of resistance in pathogen populations. We address this idea by measuring the fitness effect of a collection of rifampicin resistance mutations in the β subunit of RNA polymerase ( rpoB ) across eight strains that span the diversity of the genus Pseudomonas . We find that almost 50% of rpoB mutations have background-dependent fitness costs, demonstrating that epistatic interactions between rpoB and the rest of the genome are common. Moreover, epistasis is typically strong, and it is the dominant genetic determinant of the cost of resistance mutations. To investigate the functional basis of epistasis, and because rpoB plays a central role in transcription, we measured the effects of common rpoB mutations on transcriptional efficiency across three strains of Pseudomonas . Transcriptional efficiency correlates strongly to fitness across strains, and epistasis arises because individual rpoB mutations have differential effects on transcriptional efficiency in different genetic backgrounds.

scholarly journals The heritable activation of cryptic Suppressor-mutator elements by an active element.

Genetics ◽  
1989 ◽  
Vol 121 (3) ◽  
pp. 591-608 ◽  
Author(s):  
N Fedoroff
Keyword(s):  
Genetic Background ◽  
Active Element ◽  
Background Level ◽  
Maize Genome ◽  
Reactivation Process ◽  
Inactive Form ◽  
Order Of Magnitude ◽  
Selection For ◽  
Efficient Selection ◽  
Selection Of

Abstract A weakly active maize Suppressor-mutator (Spm-omega) element is able to heritably activate cryptic Spm elements in the maize genome. The spontaneous activation frequency, which is 1-5 x 10(-5) in the present genetic background, increases by about 100-fold in the presence of an Spm-omega and remains an order of magnitude above the background level a generation after removal of the activating Spm-omega. Sectorial somatic reactivation of cryptic elements can be detected phenotypically in kernels. Selection of such kernels constitutes an efficient selection for plants with reactivated Spm elements. Analysis of the reactivation process reveals that it is gradual and proceeds through genetically metastable intermediates that exhibit different patterns of element expression during plant development. Newly reactivated elements tend to return to an inactive form. However, the probability that an element will remain in a heritably active state increases when the element is maintained in the presence of an active Spm element for several generations.

scholarly journals PreDarwinian evolution, prebiotic change: a principle of least selection

2021 ◽  
Author(s):  
Michael Yarus
Keyword(s):  
Natural Selection ◽  
Standard Deviation ◽  
Molecular Complex ◽  
Minimal Change ◽  
Materials Chemistry ◽  
Evolutionary Path ◽  
Proportionality Constant ◽  
Selection For ◽  
The Cost ◽  
Selection Of

Evolution prior to its Darwinian era was an age of variation. Events allowed by starting materials, chemistry and physics were realized, directed by intrinsic probabilities. In this landscape, a principle of least selection defines the most probable evolutionary path. For selection from a population where x varies, the rate of x evolution dx/dt = αΔμ. μ is the population mean of the selected property x, [alpha] a proportionality constant. Explicit equations for selected change Δμ are presented. Simple results exist for frequent cases; for example, selection for x ≥ a threshold. Maximizing Δμ minimizes need for selection. Least selections for x demand maximal selection dependence on x, maximal x standard deviation σ, and maximal lower x threshold (consistent with the need for a survivor). Least selection is free of the cost of natural selection, thus can support rapid advance. Least selection also unites previous seemingly independent optima. As examples, evolution via ′starting bloc selection [prime] and ′chance utility′ (where selection spans a minimal change) and ′near-ideal reactions′ (where variable reactant supplies create easy reactions) occur via transitory paths of least selection. ′Bayesian convergence′ is guaranteed by least selection′s extremum (which sharply defines evolution′s path). [prime]Distribution fitness′ (where specific outcomes are selected among multiple concurrent variations) is least selection of rare functional minorities. Inheritance of encoded chemical capabilities first evolves because templating and catalysis are close, potentially joined in a single molecular complex. Least selection defines directions, biostructures define destinations in likely pathways of preDarwinian evolution.

scholarly journals Predation and selection for antibiotic resistance in natural environments

2016 ◽  
Vol 9 (3) ◽  
pp. 427-434 ◽  
Author(s):  
Jørgen J. Leisner ◽  
Niels O. G. Jørgensen ◽  
Mathias Middelboe
Keyword(s):  
Antibiotic Resistance ◽  
Natural Environments ◽  
Selection For
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