Spontaneous mutants derived from ΔbfmRS were isolated after selection with mecillinam or imipenem, and three isolates were analyzed for BfmRS-dependent phenotypes: EGA534 [ΔbfmRS cspC(G17AfsX21)], EGA555 [ΔbfmRS mnmA(G362S)], and EGA552 [ΔbfmRS ACX60_RS05385/(NUDIX)::ISAba1]. (A) Strains were tested for antibiotic resistance by CFE assay. Data points show geometric mean ± s.d. (mecillinam, n = 4; sulbactam, n = 2). *, P < 0.015 in unpaired t-tests comparing mutant vs WT; asterisks were stacked in the case of overlapping symbols. (B) Ability to withstand complement-mediated killing in serum was examined as in Fig 1. Lines show mean ± s.d. (n = 3). The limit of detection is indicated by the dotted line. (C) Cellular morphology of ΔbfmRS suppressor mutants. Bacteria were grown in antibiotic-free LB medium and imaged via phase-contrast microscopy. (D) Cell length was determined from n > 240 cells per strain. Red lines represent median values. Suppressor mutants differed significantly from ΔbfmRS (P < 0.0001, Mann-Whitney test). (E) Transcript levels were quantified via qPCR, and the fold change in each mutant vs the parental ΔbfmRS strain was determined. Bars show the mean value ± s.d. (n = 3). Bars marked with * had P < 0.05 (unpaired t-tests) and at least 20% difference in mean when comparing each mutant with parental ΔbfmRS.