In nature, bacteria encounter environments with fluctuating mixtures of nutrients, often at low concentrations that limit growth. Nutrient levels are influenced by physical processes such as fluid flow that either remove or renew nutrients, and bacteria adapt to nutrient availability to sustain their growth. However, efforts to study how low nutrient concentrations and rapid renewal shape microbial physiology have been challenging in the laboratory setting. To address this, Lara-Gutiérrez, Saito, Stocker and colleagues developed a millifluidic continuous culture device, which enables bacterial cultivation in complex nutrients at low micromolar concentrations with rapid renewal by continuous fluid flow. To investigate how bacteria respond to different concentrations of a nutrient mixture, the authors used
Escherichia coli and performed proteomic analyses at three concentration ranges of a mixture that contained amino acids, nucleobases and vitamins. Interestingly, at the lowest nutrient condition, cells exhibited a proteomic signature of iron scarcity, although equal and nonlimiting iron concentrations were present in all nutrient conditions. Modelling predicted lower siderophore concentrations in the millifluidic continuous culture device, which suggests that siderophore-mediated iron uptake is reduced and cells have to acquire iron through another strategy. Importantly, the authors showed that iron forms complexes with amino acids, and complexation facilitated iron uptake. On the basis of their results, the authors propose that continuous fluid flow dilutes secreted siderophores, and available amino acids then act as ligands that form complexes with iron that can be taken up and utilized by cells. However, at low nutrient concentrations, the limited availability of amino acids leads to iron shortage. In sum, the findings suggest that amino acids facilitate microbial iron acquisition in environments that exhibit low nutrient concentration and where siderophores are highly diluted.