{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:22:41Z","timestamp":1785410561174,"version":"3.56.0"},"reference-count":75,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32573557"],"award-info":[{"award-number":["32573557"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["42076095"],"award-info":[{"award-number":["42076095"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["32573557"],"award-info":[{"award-number":["32573557"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["42076095"],"award-info":[{"award-number":["42076095"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"University-Enterprise cooperation of Guangzhou project","award":["2024A03J0379"],"award-info":[{"award-number":["2024A03J0379"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Staphylococcus aureus is an important zoonotic pathogen. In recent years, it has been isolated from diseased aquatic animals, causing skin ulcers and septicemia, establishing itself as an emerging pathogen in aquaculture. Rampant antibiotic use has accelerated antimicrobial resistance, a trend that has gradually curtailed the potency of conventional antibiotic therapies, underscoring the urgent need for novel therapies. Here, we screened 20 amino acids and found that exogenous proline significantly enhances the bactericidal activity of amikacin against S. aureus. This synergistic effect extends to other aminoglycoside antibiotics, including neomycin sulfate and gentamicin, and is also effective against drug-resistant strains such as MRSA USA300. Furthermore, we evaluated the efficacy of this combination in eradicating persisters and biofilms. Mechanistically, exogenous proline potentiates amikacin-mediated killing by modulating two key bactericidal pathways. On one hand, it enhances antibiotic uptake by augmenting the proton motive force via the electron transport chain. On the other hand, it amplifies oxidative stress through a multi-pronged mechanism involving the suppression of ROS-scavenging enzymes, activation of the Fenton reaction, and reduction in intracellular nitric oxide (NO) levels, ultimately culminating in bacterial cell death. This study proposes a promising strategy for combating S. aureus in aquaculture and healthcare-associated infections.<\/jats:p>","DOI":"10.3390\/life16071070","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:54:42Z","timestamp":1782694482000},"page":"1070","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Proline Potentiates Aminoglycoside Bactericidal Efficacy Against Staphylococcus aureus"],"prefix":"10.3390","volume":"16","author":[{"given":"Bo-Hao","family":"Li","sequence":"first","affiliation":[{"name":"Department of Immunology and Microbiology & Institute of Medical Microbiology, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"},{"name":"MOE Key Laboratory of Viral Pathogenesis & Infection Prevention and Control (Jinan University), National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui-Hua","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology & Institute of Medical Microbiology, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"},{"name":"MOE Key Laboratory of Viral Pathogenesis & Infection Prevention and Control (Jinan University), National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zulifukeer","family":"Maituersong","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology & Institute of Medical Microbiology, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"},{"name":"MOE Key Laboratory of Viral Pathogenesis & Infection Prevention and Control (Jinan University), National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao-Feng","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences and Biotechnology, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences and Biotechnology, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5300-7765","authenticated-orcid":false,"given":"Yu-Bin","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology & Institute of Medical Microbiology, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"},{"name":"MOE Key Laboratory of Viral Pathogenesis & Infection Prevention and Control (Jinan University), National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e00813","DOI":"10.1002\/cbdv.202400813","article-title":"Antibiotic Resistance: Revisiting Older Antibiotics for Modern Bacterial Challenges","volume":"22","author":"Boretti","year":"2025","journal-title":"Chem. 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