Fig. 4. PnimB^G-associated metronidazole (MTZ) resistance co-occurs with fluroquinolone resistance and pandemic spread.

a Manhattan plot showing SNPs significantly associated with heme-induced metronidazole resistance (HMR). Adjusted, log-transformed p values calculated by pySEER are plotted by genome position; default statistical analyses built in pySEER were used. Both gyrA and nimB SNPs are very significantly associated with HMR. b Maximum likelihood phylogeny based on whole genome sequences from 348 isolates. Multi-locus sequence type (MLST) Clades 1-5 (inner circle), gyrA and nimB-promoter mutations (middle circle), and metronidazole susceptibility (outer circle), either heme-induced metronidazole resistant (HMR) or metronidazole susceptible (S), are shown. The gyrA, nimB-promoter mutations and associated HMR are associated with clonal groups in Clades 2 and 1, suggesting that bacteria carrying these variants have spread rapidly and/ or are sampled more densely in this population.