Data and code for: Dihydrothiazolo ring-fused 2-pyridone antimicrobial compounds effectively treat Streptococcus pyogenes skin and soft tissue infection

We have developed GmPcides from a peptidomimetic dihydrothiazolo
ring-fused 2-pyridone scaffold that have antimicrobial activities against
a broad-spectrum of Gram-positive pathogens. Here we examine the treatment
efficacy of GmPcides using skin and soft tissue infection (SSTI) and
biofilm formation models by Streptococcus pyogenes. Screening our compound
library for minimal inhibitory (MIC) and minimal bactericidal (MBC)
concentrations identified GmPcide PS757 as highly active against S.
pyogenes . Treatment of S. pyogenes biofilm with PS757 revealed robust
efficacy against all phases of biofilm formation by preventing initial
biofilm development, ceasing biofilm maturation and eradicating mature
biofilm. In a murine model of S. pyogenes SSTI, subcutaneous delivery of
PS757 resulted in reduced levels of tissue damage, decreased bacterial
burdens and accelerated rates of wound-healing, which were associated with
down-regulation of key virulence factors, including M protein and the SpeB
cysteine protease. These data demonstrate that GmPcides show considerable
promise for treating S. pyogenes infections.