Bernard Beall

My PhD and post-doctoral work centered upon facets of bacterial cell division and sporulation (1985-1993). During my 27 years at the US Centers for Disease Control and Prevention, I have focused primarily on national surveillance of circulating strains of the 3 major invasive streptococcal pathogens, S. pneumoniae, S. pyogenes, and S. agalactiae. Based upon pioneering work in the 1980s and 1990s it was evident that alterations within penicillin binding proteins (PBPs) drive increases of β-lactam minimum inhibitory concentrations (MICs) in clinical isolates of S. pneumoniae. This observation was corroborated through our whole genome sequencing algorithm that accurately predicts MICs for β-lactams in pneumococci based upon cumulative substitutions within the transpeptidase regions of PBPs 1a, 2b, and 2x. We also find that S. agalactiae strains with reduced susceptibility or nonsusceptibility to β-lactams invariably contain key substitutions within PBP2x. Incorporating a PPB2x typing system into our genomic bioinformatics pipeline for S. pyogenes led to discovery of the first known pbp2x point mutant in this species with reduced β-lactam susceptibility. Here I will describe PBP2X sequence types and associated phenotypes within the context of multi-state, population and whole genome sequence based surveillance of more than 8000 invasive S. pyogenes isolates recovered during 2015-2020.