Introduction. Streptococcus pyogenes, sometimes referred to as group A streptococcus (GAS), causes more than 700 million infections annually worldwide. GAS monomicrobial necrotizing soft tissue infections (NSTIs) can be devastating and cause substantial morbidity and mortality. Limited research has studied the GAS transcriptome in patients with monomicrobial NSTIs.
Methods. We performed RNA-seq on 47 biopsies obtained from soft tissue, muscle, or fascia from 34 human patients with monomicrobial NSTIs caused by four GAS serotypes (M1, M3, M28, and M89). We also performed comprehensive transcriptome comparisons among and between patients infected with the same or different M protein serotype. The GAS genome sequences were available for strains infecting all 34 patients.
Results. We identified substantial heterogeneity in transcriptomes across GAS serotypes, infected tissues, and hosts. Although 88% of genes were significantly associated with transcript abundance quartiles, importantly, 12% of genes were not, indicating dynamic variation in transcript abundance. Significant transcriptome differences were identified among and between strains of the same or different GAS serotypes, and also when comparing different tissue types. In some cases, virulence genes located on mobile genetic elements (MGEs) had high transcript abundance compared to other MGE-encoded genes.
Conclusions. Taken together, the data reveal a very complex relationship between GAS transcriptome, infecting M protein serotype, and infection site. These findings have implications for understanding the molecular basis of GAS-human interaction and translational research geared toward GAS vaccinology and therapeutics.