scholarly journals Antibiotic breakdown by susceptible bacteria enhances the establishment of β-lactam resistant mutants

2021 ◽  
Author(s):  
Manja Saebelfeld ◽  
Suman G Das ◽  
Jorn Brink ◽  
Arno Hagenbeek ◽  
Joachim Krug ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Theoretical Model ◽  
Enzymatic Activity ◽  
Social Interactions ◽  
Single Cells ◽  
Antibiotic Concentration ◽  
High Frequencies ◽  
Establishment Probability ◽  
Resistant Mutants

For a better understanding of the evolution of antibiotic resistance, it is imperative to study the factors that determine the initial establishment of mutant resistance alleles. In addition to the antibiotic concentration, the establishment of resistance alleles may be affected by interactions with the surrounding susceptible cells from which they derive, for instance via the release of nutrients or removal of the antibiotic. Here, we investigate the effects of social interactions with surrounding susceptible cells on the establishment of Escherichia coli mutants with increasing β-lactamase activity (i.e. the capacity to hydrolyze β-lactam antibiotics) from single cells under the exposure of the antibiotic cefotaxime on agar plates. We find that mutant establishment probability is increased in the presence of susceptible cells due to the active breakdown of the antibiotic, but the rate of breakdown by the susceptible strain is much higher than expected based on its low enzymatic activity. A detailed theoretical model suggests that this observation can be explained by cell filamentation causing delayed lysis. While susceptible cells may hamper the spread of higher-resistant β-lactamase mutants at relatively high frequencies, our findings show that they could promote establishment during their emergence.

scholarly journals Antibiotic Breakdown by Susceptible Bacteria Enhances the Establishment of β-Lactam Resistant Mutants

2021 ◽  
Vol 12 ◽  
Author(s):  
Manja Saebelfeld ◽  
Suman G. Das ◽  
Jorn Brink ◽  
Arno Hagenbeek ◽  
Joachim Krug ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Theoretical Model ◽  
Social Interactions ◽  
Single Cells ◽  
Antibiotic Concentration ◽  
Activity Increase ◽  
High Frequencies ◽  
Resistant Mutants ◽  
Mutant Cells

For a better understanding of the evolution of antibiotic resistance, it is imperative to study the factors that determine the initial establishment of mutant resistance alleles. In addition to the antibiotic concentration, the establishment of resistance alleles may be affected by interactions with the surrounding susceptible cells from which they derive, for instance via the release of nutrients or removal of the antibiotic. Here, we investigate the effects of social interactions with surrounding susceptible cells on the establishment of Escherichia coli mutants with increasing β-lactamase activity (i.e., the capacity to hydrolyze β-lactam antibiotics) from single cells under the exposure of the antibiotic cefotaxime (CTX) on agar plates. We find that relatively susceptible cells, expressing a β-lactamase with very low antibiotic-hydrolyzing activity, increase the probability of mutant cells to survive and outgrow into colonies due to the active breakdown of the antibiotic. However, the rate of breakdown by the susceptible strain is much higher than expected based on its low enzymatic activity. A detailed theoretical model suggests that this observation may be explained by cell filamentation causing delayed lysis. While susceptible cells may hamper the spread of higher-resistant β-lactamase mutants at relatively high frequencies, our findings show that they promote their initial establishment.

scholarly journals Stochastic effects on the establishment of mutants resistant to β-lactam antibiotics

2021 ◽  
Author(s):  
Manja Saebelfeld ◽  
Suman G. Das ◽  
Arno Hagenbeek ◽  
Joachim Krug ◽  
J. Arjan G.M. de Visser
Keyword(s):  
Antibiotic Resistance ◽  
Single Cell ◽  
General Reference ◽  
Stochastic Effects ◽  
Cooperative Effects ◽  
Branching Model ◽  
Establishment Probability ◽  
Quantitative Understanding ◽  
Resistant Mutants ◽  
Cell Densities

AbstractFor antibiotic resistance to arise, new resistant mutants must establish in a bacterial population before they can spread via natural selection. Understanding the stochastic factors influencing mutant establishment is crucial for a quantitative understanding of antibiotic resistance emergence. Here, we quantify the single-cell establishment probability of four Escherichia coli strains expressing β-lactamase alleles with different activity against the antibiotic cefotaxime, as a function of concentration. Using a simple branching model, we show that concentrations well below the minimal inhibitory concentration (MIC) can substantially hamper establishment, particularly for highly resistant mutants, suggesting cooperative effects due to antibiotic breakdown at high cell densities. We further show that variation among cell lineages may explain the more gradual influence of increased antibiotic concentrations on agar. Finally, we use the single-cell establishment probability to predict a strain’s MIC in the absence of social interactions, as a general reference to detect cooperative resistance effects.

scholarly journals Rapid Detection of Escherichia coli Antibiotic Susceptibility Using Live/Dead Spectrometry for Lytic Agents

2021 ◽  
Vol 9 (5) ◽  
pp. 924
Author(s):  
Julia Robertson ◽  
Cushla McGoverin ◽  
Joni R. White ◽  
Frédérique Vanholsbeeck ◽  
Simon Swift
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Rapid Detection ◽  
Inhibitory Action ◽  
Detection Method ◽  
Treatment Time ◽  
Polymyxin B ◽  
Diagnostic Techniques ◽  
Antibiotic Concentration ◽  
Syto 9

Antibiotic resistance is a serious threat to public health. The empiric use of the wrong antibiotic occurs due to urgency in treatment combined with slow, culture-based diagnostic techniques. Inappropriate antibiotic choice can promote the development of antibiotic resistance. We investigated live/dead spectrometry using a fluorimeter (Optrode) as a rapid alternative to culture-based techniques through application of the LIVE/DEAD® BacLightTM Bacterial Viability Kit. Killing was detected by the Optrode in near real-time when Escherichia coli was treated with lytic antibiotics—ampicillin and polymyxin B—and stained with SYTO 9 and/or propidium iodide. Antibiotic concentration, bacterial growth phase, and treatment time used affected the efficacy of this detection method. Quantification methods of the lethal action and inhibitory action of the non-lytic antibiotics, ciprofloxacin and chloramphenicol, respectively, remain to be elucidated.

scholarly journals Specific phenotypic, genomic, and fitness evolutionary trajectories toward antibiotic resistance induced by pesticide co-stressors in Escherichia coli

2021 ◽  
Author(s):  
Yue Xing ◽  
Xiaoxi Kang ◽  
Siwei Zhang ◽  
Yujie Men
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Selective Pressure ◽  
Fold Increase ◽  
Evolutionary Stage ◽  
Fitness Costs ◽  
Evolutionary Trajectories ◽  
Resistant Mutants ◽  
K 12 ◽  
Late Stages

To explore how co-occurring non-antibiotic environmental stressors affect evolutionary trajectories toward antibiotic resistance, we exposed susceptible Escherichia coli K-12 populations to environmentally relevant levels of pesticides and streptomycin for 500 generations. The coexposure substantially changed the phenotypic, genotypic, and fitness evolution trajectories, resulting in much stronger streptomycin resistance (>15-fold increase) of the populations. Antibiotic target modification mutations in rpsL and rsmG, which emerged and dominated at late stages of evolution, conferred the strong resistance even with less than 1% abundance, while the off-target mutations in nuoG, nuoL, glnE, and yaiW dominated at early stages only led to mild resistance (2.5 ~ 6-fold increase). Moreover, the strongly resistant mutants exhibited lower fitness costs even without the selective pressure and had lower minimal selection concentrations than the mildly resistant ones. Removal of the selective pressure did not reverse the strong resistance of coexposed populations at a later evolutionary stage. The findings suggest higher risks of the selection and propagation of strong antibiotic resistance in environments potentially impacted by antibiotics and pesticides.

scholarly journals Genomewide Screen for Modulators of Evolvability under Toxic Antibiotic Exposure

2013 ◽  
Vol 57 (7) ◽  
pp. 3453-3456 ◽  
Author(s):  
Orsolya Méhi ◽  
Balázs Bogos ◽  
Bálint Csörgő ◽  
Csaba Pál
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Iron Homeostasis ◽  
De Novo ◽  
Antibiotic Exposure ◽  
Wild Type ◽  
Content Type ◽  
Translation Fidelity ◽  
Evolution Of Resistance ◽  
Resistant Mutants

ABSTRACTAntibiotic resistance is generally selected within a window of concentrations high enough to inhibit wild-type growth but low enough for new resistant mutants to emerge. We studiedde novoevolution of resistance to ciprofloxacin in anEscherichia coliknockout library. Five null mutations had little or no effect on intrinsic antibiotic susceptibility but increased the upper antibiotic dosage to which initially sensitive populations could adapt. These mutations affect mismatch repair, translation fidelity, and iron homeostasis.

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