{"doi":"10.1101/2024.01.02.573960","title":"Dihydrothiazolo ring-fused 2-pyridone antimicrobial compounds treat <i>Streptococcus pyogenes</i> skin and soft tissue infection","abstract":"ABSTRACT 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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":493030,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9552,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":813860,"name":"Chloe L. P. Obernuefemann","orcid":null,"position":1,"is_corresponding":false},{"id":495848,"name":"Pardeep Singh","orcid":"0000-0002-2181-8085","position":2,"is_corresponding":false},{"id":681726,"name":"Jerome S. Pinkner","orcid":"0000-0002-7389-7440","position":3,"is_corresponding":false},{"id":1197372,"name":"Wei Xu","orcid":"0000-0002-7254-8273","position":4,"is_corresponding":false},{"id":471590,"name":"Taylor M. Nye","orcid":"0000-0003-4695-0485","position":5,"is_corresponding":false},{"id":401552,"name":"Karen Dodson","orcid":"0000-0001-7421-9660","position":6,"is_corresponding":false},{"id":757347,"name":"Fredrik Almqvist","orcid":"0000-0002-0504-4446","position":7,"is_corresponding":false},{"id":401555,"name":"Scott J. Hultgren","orcid":"0000-0001-8785-564X","position":8,"is_corresponding":false},{"id":913515,"name":"Michael G. Caparon","orcid":"0000-0003-1171-0772","position":9,"is_corresponding":false},{"id":828585,"name":"Zongsen Zou","orcid":"0000-0002-4770-2144","position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:09:00.148120Z","pmid":"38260261","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}