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This study investigated the impact of extracts derived from the supernatant of four lactic acid bacteria strains on factors contributing to the pathogenicity of three Staphylococcus aureus strains. The study evaluated the influence of lactic acid bacteria supernatant extracts on the growth, biofilm biomass formation, biofilm metabolic activity, and biofilm integrity of the S. aureus strains. Additionally, the impact on virulence factors (hemolysin and coagulase) was examined. Gas chromatography coupled with mass spectrometry was used to identify the bioactive compounds in the extracts, while molecular docking analyses explored potential interactions. Predominantly, the extracts contain eight 2,5-diketopiperazines, which are cyclic forms of peptides. The extracts demonstrated inhibitory effects on biofilm formation, the ability to disrupt mature biofilms, and reduce the biofilm cell metabolic activity of the S. aureus strains. Furthermore, they exhibited the ability to inhibit \u03b1-hemolysin production and reduce coagulase activity. An in silico docking analysis reveals promising interactions between 2,5-diketopiperazines and key proteins (SarA and AgrA) in S. aureus, confirming their antivirulence and antibiofilm activities. These findings suggest that 2,5-diketopiperazines could serve as a promising lead compound in the fight against antibiotic-resistant S. aureus.<\/jats:p>","DOI":"10.3390\/antibiotics13040297","type":"journal-article","created":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T14:00:23Z","timestamp":1711375223000},"page":"297","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Restraining Staphylococcus aureus Virulence Factors and Quorum Sensing through Lactic Acid Bacteria Supernatant Extracts"],"prefix":"10.3390","volume":"13","author":[{"given":"Myriam Anabel","family":"D\u00edaz","sequence":"first","affiliation":[{"name":"Instituto Superior de Investigaciones Biol\u00f3gicas (INSIBIO, CONICET-UNT), Chacabuco 461, San Miguel de Tucum\u00e1n CP 4000, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6920-0903","authenticated-orcid":false,"given":"Esteban Gabriel","family":"Vega-Hissi","sequence":"additional","affiliation":[{"name":"Instituto Multidisciplinario de Investigaciones Biol\u00f3gicas (IMIBIO-SL), Facultad de Qu\u00edmica, Bioqu\u00edmica y Farmacia, Universidad Nacional de San Luis, Ej\u00e9rcito de Los Andes 950, San Luis CP 5700, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7673-9328","authenticated-orcid":false,"given":"Mar\u00eda Amparo","family":"Bl\u00e1zquez","sequence":"additional","affiliation":[{"name":"Departament de Farmacologia, Facultat de Farm\u00e0cia i Ci\u00e8ncies de l\u2019Alimentaci\u00f3, Universitat de Val\u00e8ncia, Avd. Vicent Andr\u00e9s Estell\u00e9s s\/n, Burjasot, 46100 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4173-9499","authenticated-orcid":false,"given":"Mar\u00eda Rosa","family":"Alberto","sequence":"additional","affiliation":[{"name":"Facultad de Bioqu\u00edmica, Qu\u00edmica y Farmacia, Universidad Nacional de Tucum\u00e1n (UNT), Ayacucho 471, San Miguel de Tucum\u00e1n CP 4000, Argentina"},{"name":"Instituto de Biotecnolog\u00eda Farmac\u00e9utica y Alimentaria (INBIOFAL, CONICET-UNT), Avenida Kirchner 1900, San Miguel de Tucum\u00e1n CP 4000, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1984-5233","authenticated-orcid":false,"given":"Mario Eduardo","family":"Arena","sequence":"additional","affiliation":[{"name":"Facultad de Bioqu\u00edmica, Qu\u00edmica y Farmacia, Universidad Nacional de Tucum\u00e1n (UNT), Ayacucho 471, San Miguel de Tucum\u00e1n CP 4000, Argentina"},{"name":"Instituto de Biotecnolog\u00eda Farmac\u00e9utica y Alimentaria (INBIOFAL, CONICET-UNT), Avenida Kirchner 1900, San Miguel de Tucum\u00e1n CP 4000, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,25]]},"reference":[{"key":"ref_1","unstructured":"WHO (2024, February 07). 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