{"title":"重新利用fda批准的药物对抗抗菌素耐药性的机制框架:金黄色葡萄球菌的案例。","authors":"Daniel Sun, Victor Nizet","doi":"10.1146/annurev-pharmtox-062624-014243","DOIUrl":null,"url":null,"abstract":"<p><p>The global rise of antibiotic-resistant bacteria poses a critical threat to healthcare systems, challenging researchers to stay ahead of evolving pathogens. Among the most concerning are invasive infections caused by <i>Staphylococcus aureus</i> (SA), where morbidity and mortality remain high despite advances in care. Resistance in SA has emerged rapidly after the introduction of new antibiotics, limiting treatment options and prompting an urgent need for alternatives. While developing new antimicrobials remains essential, repurposing FDA-approved drugs-originally developed for noninfectious indications-offers a complementary strategy. These agents have known safety and pharmacokinetic profiles and may impact bacterial virulence, antibiotic susceptibility, or host immunity to improve outcomes. This review highlights recent advances in SA drug repurposing, focusing on six mechanistic categories: inhibition of virulence factors, antibiotic resensitization, enhanced susceptibility to innate immunity, host cell protection, augmentation of immune functions, and modulation of pathological inflammation. Together, these strategies offer a multifaceted framework to improve SA infection outcomes using existing therapeutics.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":" ","pages":""},"PeriodicalIF":13.1000,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A Mechanistic Framework for Repurposing FDA-Approved Drugs to Combat Antimicrobial Resistance: The Case of <i>Staphylococcus aureus</i>.\",\"authors\":\"Daniel Sun, Victor Nizet\",\"doi\":\"10.1146/annurev-pharmtox-062624-014243\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The global rise of antibiotic-resistant bacteria poses a critical threat to healthcare systems, challenging researchers to stay ahead of evolving pathogens. Among the most concerning are invasive infections caused by <i>Staphylococcus aureus</i> (SA), where morbidity and mortality remain high despite advances in care. Resistance in SA has emerged rapidly after the introduction of new antibiotics, limiting treatment options and prompting an urgent need for alternatives. While developing new antimicrobials remains essential, repurposing FDA-approved drugs-originally developed for noninfectious indications-offers a complementary strategy. These agents have known safety and pharmacokinetic profiles and may impact bacterial virulence, antibiotic susceptibility, or host immunity to improve outcomes. This review highlights recent advances in SA drug repurposing, focusing on six mechanistic categories: inhibition of virulence factors, antibiotic resensitization, enhanced susceptibility to innate immunity, host cell protection, augmentation of immune functions, and modulation of pathological inflammation. Together, these strategies offer a multifaceted framework to improve SA infection outcomes using existing therapeutics.</p>\",\"PeriodicalId\":8057,\"journal\":{\"name\":\"Annual review of pharmacology and toxicology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":13.1000,\"publicationDate\":\"2025-09-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Annual review of pharmacology and toxicology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1146/annurev-pharmtox-062624-014243\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annual review of pharmacology and toxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1146/annurev-pharmtox-062624-014243","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
A Mechanistic Framework for Repurposing FDA-Approved Drugs to Combat Antimicrobial Resistance: The Case of Staphylococcus aureus.
The global rise of antibiotic-resistant bacteria poses a critical threat to healthcare systems, challenging researchers to stay ahead of evolving pathogens. Among the most concerning are invasive infections caused by Staphylococcus aureus (SA), where morbidity and mortality remain high despite advances in care. Resistance in SA has emerged rapidly after the introduction of new antibiotics, limiting treatment options and prompting an urgent need for alternatives. While developing new antimicrobials remains essential, repurposing FDA-approved drugs-originally developed for noninfectious indications-offers a complementary strategy. These agents have known safety and pharmacokinetic profiles and may impact bacterial virulence, antibiotic susceptibility, or host immunity to improve outcomes. This review highlights recent advances in SA drug repurposing, focusing on six mechanistic categories: inhibition of virulence factors, antibiotic resensitization, enhanced susceptibility to innate immunity, host cell protection, augmentation of immune functions, and modulation of pathological inflammation. Together, these strategies offer a multifaceted framework to improve SA infection outcomes using existing therapeutics.
期刊介绍:
Since 1961, the Annual Review of Pharmacology and Toxicology has been a comprehensive resource covering significant developments in pharmacology and toxicology. The journal encompasses various aspects, including receptors, transporters, enzymes, chemical agents, drug development science, and systems like the immune, nervous, gastrointestinal, cardiovascular, endocrine, and pulmonary systems. Special topics are also featured in this annual review.