Dataset Information

Local genic base composition impacts protein production and cellular fitness.

ABSTRACT: The maintenance of a G + C content that is higher than the mutational input to a genome provides support for the view that selection serves to increase G + C contents in bacteria. Recent experimental evidence from Escherichia coli demonstrated that selection for increasing G + C content operates at the level of translation, but the precise mechanism by which this occurs is unknown. To determine the substrate of selection, we asked whether selection on G + C content acts across all sites within a gene or is confined to particular genic regions or nucleotide positions. We systematically altered the G + C contents of the GFP gene and assayed its effects on the fitness of strains harboring each variant. Fitness differences were attributable to the base compositional variation in the terminal portion of the gene, suggesting a connection to the folding of a specific protein feature. Variants containing sequence features that are thought to result in rapid translation, such as low G + C content and high levels of codon adaptation, displayed highly reduced growth rates. Taken together, our results show that purifying selection acting against A and T mutations most likely results from their tendency to increase the rate of translation, which can perturb the dynamics of protein folding.

SUBMITTER: Quandt EM

PROVIDER: S-EPMC5774297 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Local genic base composition impacts protein production and cellular fitness.

Quandt Erik M EM Traverse Charles C CC Ochman Howard H

PeerJ 20180116

The maintenance of a G + C content that is higher than the mutational input to a genome provides support for the view that selection serves to increase G + C contents in bacteria. Recent experimental evidence from <i>Escherichia coli</i> demonstrated that selection for increasing G + C content operates at the level of translation, but the precise mechanism by which this occurs is unknown. To determine the substrate of selection, we asked whether selection on G + C content acts across all sites w ...[more]

PMID: 29362699

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Project description:BACKGROUND: The prevalence of obesity increased while certain measures of physical fitness deteriorated in preschool children in China over the past decade. This study tested the effectiveness of a multifaceted intervention that integrated childcare center, families, and community to promote healthy growth and physical fitness in preschool Chinese children. METHODS: This 12-month study was conducted using a quasi-experimental pretest/posttest design with comparison group. The participants were 357 children (mean age = 4.5 year) enrolled in three grade levels in two childcare centers in Beijing, China. The intervention included: 1) childcare center intervention (physical activity policy changes, teacher training, physical education curriculum and food services training), 2) family intervention (parent education, internet website for support, and family events), and 3) community intervention (playground renovation and community health promotion events). The study outcome measures included body composition (percent body fat, fat mass, and muscle mass), Body Mass Index (BMI) and BMI z-score and physical fitness scores in 20-meter agility run (20M-AR), broad jump for distance (BJ), timed 10-jumps, tennis ball throwing (TBT), sit and reach (SR), balance beam walk (BBW), 20-meter crawl (20M-C)), 30-meter sprint (30M-S)) from a norm referenced test. Measures of process evaluation included monitoring of children's physical activity (activity time and intensity) and food preparation records, and fidelity of intervention protocol implementation. RESULTS: Children in the intervention center significantly lowered their body fat percent (-1.2%, p < 0.0001), fat mass (-0.55 kg, p <0.0001), and body weight (0.36 kg, p <0.02) and increased muscle mass (0.48 kg, p <0.0001), compared to children in the control center. They also improved all measures of physical fitness except timed 10-jumps (20M-AR: -0.74 seconds, p < 0.0001; BJ: 8.09 cm, p < 0.0001; TBT: 0.52 meters, p < 0.006; SR: 0.88 cm, p < 0.03; BBW: -2.02 seconds, p <0.0001; 30M-S: -0.45 seconds, p < 0.02; 20M-C: -3.36 seconds, p < 0.0001). Process evaluation data showed that the intervention protocol was implemented with high fidelity. CONCLUSIONS: The study demonstrated that a policy-driven multi-faceted intervention can improve preschool children's body composition and physical fitness. Program efficacy should be tested in a randomized trial. TRIAL REGISTRATION: ChiCTR-ONRC-14004143.

Project description:Biosynthetic gene clusters (BGCs) encoding the production of bacteriocins are widespread among bacterial isolates and are important genetic determinants of competitive fitness within a given habitat. Staphylococci produce a tremendous diversity of compounds, and the corresponding BGCs are frequently associated with mobile genetic elements, suggesting gain and loss of biosynthetic capacity. Pharmaceutical biology has shown that compound production in heterologous hosts is often challenging, and many BGC recipients initially produce small amounts of compound or show reduced growth rates. To assess whether transfer of BGCs between closely related Staphylococcus aureus strains can be instantly effective or requires elaborate metabolic adaptation, we investigated the intraspecies transfer of a BGC encoding the ribosomally synthesized and posttranslationally modified peptide (RiPP) micrococcin P1 (MP1). We found that acquisition of the BGC by S. aureus RN4220 enabled immediate MP1 production but also imposed a metabolic burden, which was relieved after prolonged cultivation by adaptive mutation. We used a multiomics approach to study this phenomenon and found adaptive evolution to select for strains with increased activity of the tricarboxylic acid cycle (TCA), which enhanced metabolic fitness and levels of compound production. Metabolome analysis revealed increases of central metabolites, including citrate and α-ketoglutarate in the adapted strain, suggesting metabolic adaptation to overcome the BGC-associated growth defects. Our results indicate that BGC acquisition requires genetic and metabolic predispositions, allowing the integration of bacteriocin production into the cellular metabolism. Inappropriate metabolic characteristics of recipients can entail physiological burdens, negatively impacting the competitive fitness of recipients within natural bacterial communities. IMPORTANCE Human microbiomes are critically associated with human health and disease. Importantly, pathogenic bacteria can hide in human-associated communities and can cause disease when the composition of the community becomes unbalanced. Bacteriocin-producing commensals are able to displace pathogens from microbial communities, suggesting that their targeted introduction into human microbiomes might prevent pathogen colonization and infection. However, to develop probiotic approaches, strains are needed that produce high levels of bioactive compounds and retain cellular fitness within mixed bacterial communities. Our work offers insights into the metabolic burdens associated with the production of the bacteriocin micrococcin P1 and highlights evolutionary strategies that increase cellular fitness in the context of production. Metabolic adaptations are most likely broadly relevant for bacteriocin producers and need to be considered for the future development of effective microbiome editing strategies.

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Local genic base composition impacts protein production and cellular fitness.

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Local genic base composition impacts protein production and cellular fitness.

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