There’s a New Strep in Town

The gene encoding the M protein is known as “emm” and strep bacteria with the emm gene are distinguished based on variations in the M protein sequence in its emm gene. In essence, it’s a genetic marker used to identify different strains of strep bacteria. One SDSE emm type—stG62647—has been shown to cause severe diseases, including necrotizing soft-tissue infections and osteoarticular bone infections, but little is known of its pathogenic mechanisms. To increase understanding of the molecular pathogenesis of this dangerous SDSE emm type, a team of researchers led by James M. Musser, MD, PhD, Chair of the Department of Pathology and Genomic Medicine, used genomic sequencing, mouse virulence assays, and bacterial transcriptomic analysis. Recently published in the ASM Journal, the team highlighted the complexity of host-pathogen interactions in this surging SDSE emm type. “Given its rapidly emerging importance to human health, our limited understanding of SDSE molecular pathogenesis is remarkable,” said Jesus M. Eraso, PhD, Assistant Research Professor of Pathology and Genomic Medicine and first author on the study.

To increase understanding of stG62647 isolate population genomics, the team sequenced the genomes to closure by combining Illumina paired-end short-read and Oxford Nanopore long-read data. The vast majority of the stG62647 isolates differed from one another by an average of only 240 core-genome single nucleotide polymorphisms (SNPs). Using an established model of necrotizing myositis, the team tested these genetically closely related stG62647 isolates for virulence. They discovered something unexpected—a broad spectrum of virulence phenotypes—with near-mortality rates ranging from 20% to 95%. “The significant variation was unexpected, given the isolates’ very close genetic relationships,” said Musser. “Transcriptome analysis of stG62647 isolates responsible for the lowest and highest near-mortality rates indicated the use of multiple molecular pathways to change virulence level.” Results from this integrative analysis provide extensive new information about an important emerging human bacterial strain that will help advance vaccine and therapeutic work in this field. Musser and Eraso’s collaborators on this study included Randall J. Olsen, MD, PhD, S. Wesley Long, MD, PhD and Ryan Gadd with the Center for Infectious Diseases at Houston Methodist, and Sarrah Boukthir, Ahmad Faili and Samer Kayal from Université Rennes in France.