Dataset Information

Negative feedback increases information transmission, enabling bacteria to discriminate sublethal antibiotic concentrations.

ABSTRACT: In the cell, noise constrains information transmission through signaling pathways and regulatory networks. There is growing evidence that the channel capacity of cellular pathways is limited to a few bits, questioning whether cells quantify external stimuli or rely on threshold detection and binary on/off decisions. Here, using fluorescence microscopy and information theory, we analyzed the ability of the transcriptional regulator TetR to sense and quantify the antibiotic tetracycline. The results showed that noise filtering by negative feedback increased information transmission up to 2 bits, generating a graded response able to discriminate different antibiotic concentrations. This response matched the antibiotic subinhibitory selection window, suggesting that information transmission through TetR is optimized to quantify sublethal antibiotic levels. Noise filtering by negative feedback may thus boost the discriminative power of cellular sensors, enabling signal quantification.

SUBMITTER: Ruiz R

PROVIDER: S-EPMC6261649 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Negative feedback increases information transmission, enabling bacteria to discriminate sublethal antibiotic concentrations.

Ruiz Raul R de la Cruz Fernando F Fernandez-Lopez Raul R

Science advances 20181128 11

In the cell, noise constrains information transmission through signaling pathways and regulatory networks. There is growing evidence that the channel capacity of cellular pathways is limited to a few bits, questioning whether cells quantify external stimuli or rely on threshold detection and binary on/off decisions. Here, using fluorescence microscopy and information theory, we analyzed the ability of the transcriptional regulator TetR to sense and quantify the antibiotic tetracycline. The resul ...[more]

PMID: 30498777

Similar Datasets

Project description:Adaptive evolutionary processes are constrained by the availability of mutations which cause a fitness benefit and together make up the fitness landscape, which maps genotype space onto fitness under specified conditions. Experimentally derived fitness landscapes have demonstrated a predictability to evolution by identifying limited "mutational routes" that evolution by natural selection may take between low and high-fitness genotypes. However, such studies often utilize indirect measures to determine fitness. We estimated the competitive fitness of mutants relative to all single-mutation neighbors to describe the fitness landscape of three mutations in a β-lactamase enzyme. Fitness assays were performed at sublethal concentrations of the antibiotic cefotaxime in a structured and unstructured environment. In the unstructured environment, the antibiotic selected for higher-resistance types-but with an equivalent fitness for a subset of mutants, despite substantial variation in resistance-resulting in a stratified fitness landscape. In contrast, in a structured environment with a low antibiotic concentration, antibiotic-susceptible genotypes had a relative fitness advantage, which was associated with antibiotic-induced filamentation. These results cast doubt that highly resistant genotypes have a unique selective advantage in environments with subinhibitory concentrations of antibiotics and demonstrate that direct fitness measures are required for meaningful predictions of the accessibility of evolutionary routes. IMPORTANCE The evolution of antibiotic-resistant bacterial populations underpins the ongoing antibiotic resistance crisis. We aim to understand how antibiotic-degrading enzymes can evolve to cause increased resistance, how this process is constrained, and whether it can be predictable. To this end, competition experiments were performed with a combinatorially complete set of mutants of a β-lactamase gene subject to subinhibitory concentrations of the antibiotic cefotaxime. While some mutations confer on their hosts high resistance to cefotaxime, in competition these mutations do not always confer a selective advantage. Specifically, high-resistance mutants had equivalent fitnesses despite different resistance levels and even had selective disadvantages under conditions involving spatial structure. Together, our findings suggest that the relationship between resistance level and fitness at subinhibitory concentrations is complex; predicting the evolution of antibiotic resistance requires knowledge of the conditions that select for resistant genotypes and the selective advantage evolved types have over their predecessors.

Project description:BackgroundQuantification of acquisition routes of antibiotic resistant bacteria (ARB) is pivotal for understanding transmission dynamics and designing cost-effective interventions. Different methods have been used to quantify the importance of transmission routes, such as relative risks, odds ratios (OR), genomic comparisons and basic reproduction numbers. We systematically reviewed reported estimates on acquisition routes' contributions of ARB in humans, animals, water and the environment and assessed the methods used to quantify the importance of transmission routes.MethodsPubMed and EMBASE were searched, resulting in 6054 articles published up until January 1st, 2019. Full text screening was performed on 525 articles and 277 are included.ResultsWe extracted 718 estimates with S. aureus (n = 273), E. coli (n = 157) and Enterobacteriaceae (n = 99) being studied most frequently. Most estimates were derived from statistical methods (n = 560), mainly expressed as risks (n = 246) and ORs (n = 239), followed by genetic comparisons (n = 85), modelling (n = 62) and dosage of ARB ingested (n = 17). Transmission routes analysed most frequently were occupational exposure (n = 157), travelling (n = 110) and contacts with carriers (n = 83). Studies were mostly performed in the United States (n = 142), the Netherlands (n = 87) and Germany (n = 60). Comparison of methods was not possible as studies using different methods to estimate the same route were lacking. Due to study heterogeneity not all estimates by the same method could be pooled.ConclusionDespite an abundance of published data the relative importance of transmission routes of ARB has not been accurately quantified. Links between exposure and acquisition are often present, but the frequency of exposure is missing, which disables estimation of transmission routes' importance. To create effective policies reducing ARB, estimates of transmission should be weighed by the frequency of exposure occurrence.

Dataset Information

Negative feedback increases information transmission, enabling bacteria to discriminate sublethal antibiotic concentrations.

Publications

Negative feedback increases information transmission, enabling bacteria to discriminate sublethal antibiotic concentrations.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets