Antibiotic resistance is a major global health issue due to the overuse and misuse of antibiotics in human and veterinary medicine and agriculture. This study shows that resistant bacteria can be selected at very low antibiotic concentrations, much lower than previously thought. Using sensitive competition experiments, the researchers found that resistant bacteria can be enriched even when present at very low initial fractions. They also demonstrated that de novo resistant mutants can be selected at sub-MIC concentrations of antibiotics. A mathematical model was developed to predict how quickly such mutants would take over in a susceptible population. These findings suggest that low antibiotic concentrations in natural environments play a significant role in the selection and maintenance of resistance in bacterial populations. The study highlights the importance of reducing antibiotic pollution to prevent the spread of resistance. The results also indicate that antibiotic concentrations in natural environments, such as aquatic and soil environments, can be sufficient to maintain resistance. The study shows that even low levels of antibiotics can select for resistant bacteria, which has implications for the development of resistance in bacterial pathogens. The findings challenge the traditional view of the mutant selection window and suggest that the biologically relevant sub-MIC selective window is much wider. The study also shows that de novo resistant mutants can be selected from a susceptible population at low antibiotic concentrations. The results emphasize the need for measures to reduce antibiotic levels in the environment and to use treatment regimens that avoid prolonged sub-MIC levels of antibiotics.Antibiotic resistance is a major global health issue due to the overuse and misuse of antibiotics in human and veterinary medicine and agriculture. This study shows that resistant bacteria can be selected at very low antibiotic concentrations, much lower than previously thought. Using sensitive competition experiments, the researchers found that resistant bacteria can be enriched even when present at very low initial fractions. They also demonstrated that de novo resistant mutants can be selected at sub-MIC concentrations of antibiotics. A mathematical model was developed to predict how quickly such mutants would take over in a susceptible population. These findings suggest that low antibiotic concentrations in natural environments play a significant role in the selection and maintenance of resistance in bacterial populations. The study highlights the importance of reducing antibiotic pollution to prevent the spread of resistance. The results also indicate that antibiotic concentrations in natural environments, such as aquatic and soil environments, can be sufficient to maintain resistance. The study shows that even low levels of antibiotics can select for resistant bacteria, which has implications for the development of resistance in bacterial pathogens. The findings challenge the traditional view of the mutant selection window and suggest that the biologically relevant sub-MIC selective window is much wider. The study also shows that de novo resistant mutants can be selected from a susceptible population at low antibiotic concentrations. The results emphasize the need for measures to reduce antibiotic levels in the environment and to use treatment regimens that avoid prolonged sub-MIC levels of antibiotics.