Fig. 3

Deleting liaS of the LiaFSR three-component sensor system in S. pneumoniae increases sensitivity to fluoroquinolone treatment through the upregulation of the LiaR regulon.

A The LiaFSR operon consists of three genes, liaF a proposed signal sensor, liaS (HK) and liaR (RR). B Growth curves of deletion mutants ΔliaF, ΔliaR and ΔliaFSR treated with sub-lethal dose of CIP showed sensitivity equal to wild-type (WT). Only the ∆liaS mutant showed increased sensitivity to CIP. C Complementation of liaS restored CIP sensitivity back to WT levels. D RNA-seq revealed a set of genes upregulated in a ∆liaS mutant, including the entire known LiaR regulon, highlighted by a black outline. Statistical significance was defined as |log₂FC|> 1, and P_adj < 0.05 (DESeq2³² differential enrichment analysis using a negative binomial generalized linear model with two-tailed P values adjusted for false discovery rate (FDR)). Source data available in Supplementary Data 2. E At 40 °C, ∆liaS mutants are more susceptible to CIP than WT and the ∆liaR mutant. F Overexpression of spxA2 from an IPTG-inducible promoter by addition of IPTG (dashed line) caused increased sensitivity to a sub-lethal concentration of CIP. Growth curve data represent the mean ± SEM of three biological replicates. Source data are provided as a Source Data file.