Bacterial cells can show reduced susceptibility to antibiotics owing to phenotypic variability as, for example, observed for slow-growing antibiotic persister cells. Łapińska et al. now find that fast-growing bacteria can also evade antibiotic action without developing resistance mutations owing to phenotypic reduced drug accumulation. The authors used fluorescent antibiotic probes and microfluidics to analyse the antibiotic susceptibility of single cells. Depending on the specific antibiotic and bacterial species studied, they found that individual cells showed delayed or reduced accumulation of the antibiotics. Further mechanistic work focusing on Escherichia coli and a macrolide antibiotic confirmed that reduced accumulation indeed led to increased cell survival and that this phenomenon affected fast-growing cells, which had more ribosomes (the target of the antibiotic) and efflux pumps than slower-growing cells. Further work is needed to determine whether similar mechanisms apply to other antibiotics and other bacterial species.
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