{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T20:28:48Z","timestamp":1792009728800,"version":"4.4.0"},"reference-count":56,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T00:00:00Z","timestamp":1725408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Streptococcus pyogenes, commonly known as Group A Streptococcus (GAS), is a significant human pathogen responsible for a wide range of diseases, from mild pharyngitis to severe conditions such as necrotizing fasciitis and toxic shock syndrome. The increasing antibiotic resistance, especially against macrolide antibiotics, poses a challenge to the effective treatment of these infections. This paper reviews the current state and mechanisms of antibiotic resistance in S. pyogenes. Furthermore, molecular targets for developing anti-virulence agents, which aim to attenuate virulence rather than killing it outright, are explored. This review specifically focuses on virulence regulators, proteins that coordinate the expression of multiple virulence factors in response to environmental signals, playing a crucial role in the pathogen\u2019s ability to cause disease. Key regulatory systems, such as RopB, Mga, CovRS, and the c-di-AMP signaling system, are discussed for their roles in modulating virulence gene expression. Additionally, potential molecular target sites for the development of anti-virulence agents are suggested. By concentrating on these regulatory pathways, it is proposed that anti-virulence strategies could enhance the effectiveness of existing antibiotics and reduce the selective pressure that drives the development of resistance.<\/jats:p>","DOI":"10.3390\/genes15091166","type":"journal-article","created":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T02:25:49Z","timestamp":1725416749000},"page":"1166","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Molecular Targets in Streptococcus pyogenes for the Development of Anti-Virulence Agents"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6680-4966","authenticated-orcid":false,"given":"Kyu Hong","family":"Cho","sequence":"first","affiliation":[{"name":"Department of Biology, Indiana State University, 600 Chestnut St. S224, Terre Haute, IN 47809, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1001\/jama.2018.19283","article-title":"Evaluation and Management of Penicillin Allergy: A Review","volume":"321","author":"Shenoy","year":"2019","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1097\/00005537-199705000-00016","article-title":"Intracellular reservoir of Streptococcus pyogenes in vivo: A possible explanation for recurrent pharyngotonsillitis","volume":"107","author":"Osterlund","year":"1997","journal-title":"Laryngoscope"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Thulin, P., Johansson, L., Low, D.E., Gan, B.S., Kotb, M., McGeer, A., and Norrby-Teglund, A. 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