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Multiple Novel Traits without Immediate Benefits Originate in Bacteria Evolving on Single Antibiotics.

ABSTRACT: How new traits originate in evolution is a fundamental question of evolutionary biology. When such traits arise, they can either be immediately beneficial in their environment of origin, or they may become beneficial only in a future environment. Compared to immediately beneficial novel traits, novel traits without immediate benefits remain poorly studied. Here we use experimental evolution to study novel traits that are not immediately beneficial but that allow bacteria to survive in new environments. Specifically, we evolved multiple E. coli populations in five antibiotics with different mechanisms of action, and then determined their ability to grow in more than 200 environments that are different from the environment in which they evolved. Our populations evolved viability in multiple environments that contain not just clinically relevant antibiotics, but a broad range of antimicrobial molecules, such as surfactants, organic and inorganic salts, nucleotide analogues and pyridine derivatives. Genome sequencing of multiple evolved clones shows that pleiotropic mutations are important for the origin of these novel traits. Our experiments, which lasted fewer than 250 generations, demonstrate that evolution can readily create an enormous reservoir of latent traits in microbial populations. These traits can facilitate adaptive evolution in a changing world.

SUBMITTER: Karve S

PROVIDER: S-EPMC8789282 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceAcute sore throat poses a significant burden on primary care and is a source of inappropriate antibiotic prescribing. Corticosteroids could be an alternative symptomatic treatment.ObjectiveTo assess the clinical effectiveness of oral corticosteroids for acute sore throat in the absence of antibiotics.Design, setting, and participantsDouble-blind, placebo-controlled randomized trial (April 2013-February 2015; 28-day follow-up completed April 2015) conducted in 42 family practices in South and West England, enrolled 576 adults recruited on the day of presentation to primary care with acute sore throat not requiring immediate antibiotic therapy.InterventionsSingle oral dose of 10 mg of dexamethasone (n = 293) or identical placebo (n = 283).Main outcomes and measuresPrimary: proportion of participants experiencing complete resolution of symptoms at 24 hours. Secondary: complete resolution at 48 hours, duration of moderately bad symptoms (based on a Likert scale, 0, normal; 6, as bad as it could be), visual analog symptom scales (0-100 mm; 0, no symptom to 100, worst imaginable), health care attendance, days missed from work or education, consumption of delayed antibiotics or other medications, adverse events.ResultsAmong 565 eligible participants who were randomized (median age, 34 years [interquartile range, 26.0-45.5 year]; 75.2% women; 100% completed the intervention), 288 received dexamethasone; 277, placebo. At 24 hours, 65 participants (22.6%) in the dexamethasone group and 49 (17.7%) in the placebo group achieved complete resolution of symptoms, for a risk difference of 4.7% (95% CI, -1.8% to 11.2%) and a relative risk of 1.28 (95% CI; 0.92 to 1.78; P = .14). At 24 hours, participants receiving dexamethasone were not more likely than those receiving placebo to have complete symptom resolution. At 48 hours, 102 participants (35.4%) in the dexamethasone group vs 75 (27.1%) in the placebo group achieved complete resolution of symptoms, for a risk difference of 8.7% (95% CI, 1.2% to 16.2%) and a relative risk of 1.31 (95% CI, 1.02 to 1.68; P = .03). This difference also was observed in participants not offered delayed antibiotic prescription, for a risk difference of 10.3% (95% CI, 0.6% to 20.1%) and a relative risk of 1.37 (95% CI, 1.01 to 1.87; P = .046). There were no significant differences in any other secondary outcomes.Conclusions and relevanceAmong adults presenting to primary care with acute sore throat, a single dose of oral dexamethasone compared with placebo did not increase the proportion of patients with resolution of symptoms at 24 hours. However, there was a significant difference at 48 hours.Trial registrationisrctn.org Identifier: ISRCTN17435450.

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Multiple Novel Traits without Immediate Benefits Originate in Bacteria Evolving on Single Antibiotics.

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