Streptomycin and nalidixic acid elevate the spontaneous genome-wide mutation rate in Escherichia coli

Abstract

Since antibiotic resistance is a growing public health problem worldwide, it is important to understand how antibiotics and spontaneous mutations cooperate and shape the genome-wide mutation rate and spectrum. Here, we quantitatively evaluate genome-wide mutational profiles of Escherichia coli after long-term subinhibitory exposure to a broad-spectrum (streptomycin) and a narrow-spectrum antibiotic (nalidixic acid), using a mutation accumulation design combined with whole-genome resequencing of replicate lines as a mutagenicity test. We determined that, while the genome-wide mutation rate is slightly higher in the streptomycin-treated lines compared to the control lines, there is a significant increase in the nalidixic acid-treated lines. Our findings suggest that both broad and narrow-spectrum antibiotics may elevate the mutation rates in E. coli, but mechanisms of action may affect the consequence, thus contribute to accelerating the rate of adaptation and conferring antibiotic resistance.

Keywords: Antibiotic resistance; Mutagenicity test; Mutation accumulation; Mutation spectrum.