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 ..., RNA Sequencing. Microplate (96-well) culture in C medium was conducted as described above with the addition of 0.4 µM PS757 or vehicle (DMSO). At 24 hrs, multiple wells were harvested and pooled for further processing, with the experiment repeated in triplicate. Extraction of RNA utilized the Direct-zol RNA Miniprep Plus Kit (Zymo Research, R2072) with the quality of the purified RNA determined by spectroscopy (NanoDrop 2000, Thermo Fisher). Libraries for Illumina sequencing were prepared using the FastSelect RNA kit (Qiagen, 334222), according to the manufacture’s protocol and sequences determined using an Illumina NovaSeq 6000. Basecalls and demultiplexing were performed with Illumina’s bcl2fastq software and a custom python demultiplexing program with a maximum of one mismatch in the indexing read. RNA-seq reads were then aligned to the Ensembl release 101 primary assembly with STAR version 2.7.9a (1). Gene counts were derived from the number of uniquely aligned unambiguous reads by ..., , **Title of Dataset:** Data and code for: Dihydrothiazolo ring-fused 2-pyridone antimicrobial compounds effectively treat *Streptococcus pyogenes* skin and soft tissue infection

We have submitted our raw data (Differential_Expression_PCA) and R script (RNASeq_PCA). Access this data on Dryad (10.5061/dryad.pvmcvdntj).

**Descriptions**

·       *Sample*: two group of samples. (1) GP757: RNA-seq analysis on *Streptococcus pyogenes* cells under the treatment of GmPcide PS757. This is the experimental group. (2) DMSO: RNA-seq analysis on *Streptococcus pyogenes* cells under the treatment of DMSO. This the control group.  

·       *Row 1*: gene names. (1) Genes with annotated protein functions, e.g., *aroE_1*. (2) Genes annotated as hypothetical protein, e.g., NA.

·       *Row 2~7*: Values representing the differential expression levels of *Streptococcus pyogenes* genes under two different treatment conditions, GP757 and DMSO.

**Key information sources**

Differential expression levels of...