Figure 1. RNA polymerase-mediated reduced cephalosporin susceptibility among gonococcal isolates.
Maximum likelihood phylogeny of the 1102 isolates of the GISP dataset and one United Kingdom isolate (GCPH44). Most high-level reduced cephalosporin susceptibility (MIC ≥0.125 μg/mL) in this dataset is associated with the mosaic penA XXXIV allele, but some isolates with high MICs lack this allele. In four of these isolates – GCGS1095, GCGS1014, GCGS1013 (inset, red-marked leaves) and the U.K. isolate GCPH44 (orange arrow) – CRORS is caused by mutations in the RNA polymerase holoenzyme. Transformation of the CRORS allele rpoB1 from GCGS1095 confers phenotypic reduced susceptibility to the phylogenetic neighbor GCGS0457 (inset, pink-marked leaf) and to other susceptible clinical isolates (black arrowheads). The isolate GCGS0364 (gray arrowhead, denoted with *) spontaneously develops CRORS via rpoB mutation in vitro.