{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T12:28:38Z","timestamp":1787228918975,"version":"build-2736575974"},"reference-count":189,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Antimicrobial resistance is a critical global public health challenge, with drug-resistant infections contributing to more than one million deaths annually. The widespread dissemination of multidrug-resistant bacteria poses a severe threat to the management of infectious diseases. Bacterial evolution via genetic mutation and horizontal gene transfer diminishes antimicrobial efficacy, often leading to therapeutic failure, increased morbidity and mortality. However, the development of novel antibiotics lags far behind the rapid evolution of drug-resistant bacteria. Therefore, scientists worldwide have committed to exploring alternative therapeutic strategies for bacterial infections. The key question is which strategy holds the greatest promise of addressing the predicament of traditional antibiotics and being recognized as \u201cnext-generation anti-infective drugs\u201d. This narrative review summarizes several of the most promising alternative treatment strategies against bacterial infections, emphasizing the core strengths and limitations of each strategy. A critical comparative analysis reveals that no single strategy can simultaneously satisfy the demands of acute therapy, broad patient coverage, and resistance evasion, underscoring the need for context-dependent and sequential deployment. Moreover, among these alternatives, anti-virulence therapeutic strategies, particularly those targeting the bacterial quorum sensing (QS) system, represent a major and extensively studied approach, although their clinical translation remains nascent. This review delineates the molecular mechanisms and therapeutic potential of QS-targeting anti-virulence agents. Furthermore, we candidly assess the extant biological, pharmacological, and clinical barriers impeding their clinical translation, providing perspectives on future research directions to harness these next-generation anti-infective paradigms effectively.<\/jats:p>","DOI":"10.3389\/fcimb.2026.1935576","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T12:02:26Z","timestamp":1787227346000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Next-generation anti-infective drugs in the post-antibiotic era: focusing on anti-virulence agents targeting the bacterial quorum sensing system"],"prefix":"10.3389","volume":"16","author":[{"given":"Xin","family":"Hu","sequence":"first","affiliation":[{"name":"Clinical Medical College & Affiliated Hospital of Chengdu University, Chengdu University","place":["Chengdu, China"]},{"name":"Antibiotics Innovation and Resistance Control Key Laboratory of Sichuan Province, School of Pharmacy, Chengdu University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yuan","sequence":"additional","affiliation":[{"name":"Antibiotics Innovation and Resistance Control Key Laboratory of Sichuan Province, School of Pharmacy, Chengdu University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyong","family":"Yang","sequence":"additional","affiliation":[{"name":"Clinical Medical College & Affiliated Hospital of Chengdu University, Chengdu University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwen","family":"Chu","sequence":"additional","affiliation":[{"name":"Antibiotics Innovation and Resistance Control Key Laboratory of Sichuan Province, School of Pharmacy, Chengdu University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Huang","sequence":"additional","affiliation":[{"name":"Antibiotics Innovation and Resistance Control Key Laboratory of Sichuan Province, School of Pharmacy, Chengdu University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Antibiotics Innovation and Resistance Control Key Laboratory of Sichuan Province, School of Pharmacy, Chengdu University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1186\/s13054-020-2792-z","article-title":"Efficacy, immunogenicity, and safety of IC43 recombinant Pseudomonas aeruginosa vaccine in mechanically ventilated intensive care patients-a randomized clinical trial","volume":"24","author":"Adlbrecht","year":"2020","journal-title":"Crit. 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