{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:20:10Z","timestamp":1785410410981,"version":"3.56.0"},"posted":{"date-parts":[[2025,7,31]]},"group-title":"Microbiology","reference-count":106,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["R00AI151080"],"award-info":[{"award-number":["R00AI151080"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["K12GM119955"],"award-info":[{"award-number":["K12GM119955"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,7,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Polymicrobial communities where bacteria must compete with each other to persist can serve as a source of uncharacterized antibacterial compounds to develop drugs for the treatment of drug-resistant infections. This study investigates interbacterial competition between bacteria found in the oral cavity, where\n                  <jats:italic>Streptococcus<\/jats:italic>\n                  species comprise a large portion of the resident oral microbiota and\n                  <jats:italic>Enterococcus faecalis<\/jats:italic>\n                  is a pathobiont that is commonly found in root canal infections. We used co-cultures to determine whether oral Streptococci and\n                  <jats:italic>E. faecalis<\/jats:italic>\n                  compete with each other. Our experiments revealed that multiple strains of\n                  <jats:italic>Streptococcus mutans<\/jats:italic>\n                  , an important cariogenic bacterium, kill vancomycin-resistant\n                  <jats:italic>Enterococcus<\/jats:italic>\n                  and other Gram-positive bacteria, including\n                  <jats:italic>Staphylococcus epidermidis<\/jats:italic>\n                  , and methicillin-resistant\n                  <jats:italic>Staphylococcus aureus<\/jats:italic>\n                  . Further, inhibition of Gram-positive bacteria by some strains of\n                  <jats:italic>S. mutans<\/jats:italic>\n                  requires the production of the non-ribosomal cyclic lipopeptide mutanobactin, while another strain inhibits independent of mutanobactin. We determined that\n                  <jats:italic>S. mutans<\/jats:italic>\n                  mutanobactin production increases target cell membrane permeability and that killing is contact-dependent. We also determined that an\n                  <jats:italic>E. faecalis<\/jats:italic>\n                  virulence factor, the secreted protease gelatinase (GelE), is required for recovery from mutanobactin-mediated killing. Additionally, data show that\n                  <jats:italic>S. mutans<\/jats:italic>\n                  mutanobactin production prevents and kills\n                  <jats:italic>E. faecalis<\/jats:italic>\n                  biofilms. Together, this work demonstrates how natural products from a common oral bacterium contribute to competition in polymicrobial environments, which will inform future strategies to treat and prevent bacterial infections.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>IMPORTANCE<\/jats:title>\n                  <jats:p>\n                    Antimicrobial resistance requires new therapeutics to treat drug-resistant infections. Novel antimicrobial compounds can be discovered in polymicrobial communities, where bacterial natural products promote competitive fitness. The oral cavity hosts a microbial consortium, and we investigated interactions between oral streptococci and\n                    <jats:italic>Enterococcus faecalis<\/jats:italic>\n                    , a common root canal infection isolate. We demonstrate antibacterial activity of streptococcal mutanobactin against Gram-positive pathogens, including antibiotic-resistant isolates. We further show that the\n                    <jats:italic>E. faecalis<\/jats:italic>\n                    virulence factor gelatinase promotes recovery from mutanobactin-mediated killing, and that mutanobactin prevents and kills\n                    <jats:italic>E. faecalis<\/jats:italic>\n                    biofilms. By probing interactions between bacteria that occupy the same niche and characterizing antibacterial activity of a bacterial product, this work contributes to broader efforts to identify and develop antibiotics to treat clinically relevant drug-resistant infections.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.07.31.667707","type":"posted-content","created":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T05:17:04Z","timestamp":1754025424000},"source":"Crossref","is-referenced-by-count":1,"title":["Streptococcal natural products mediate interspecies competition with Gram-positive bacterial pathogens"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5415-940X","authenticated-orcid":false,"given":"Ruth Y.","family":"Isenberg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celine W.","family":"Sackih","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0524-8289","authenticated-orcid":false,"given":"Julia L. E.","family":"Willett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025080409150902000_2025.07.31.667707v1.1","doi-asserted-by":"publisher","DOI":"10.1086\/533452"},{"key":"2025080409150902000_2025.07.31.667707v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-024-01054-w"},{"key":"2025080409150902000_2025.07.31.667707v1.3","unstructured":"CDC. 2025. CDC Partners Estimate Healthcare Cost of Antimicrobial-resistant Infections. Antimicrobial Resistance. https:\/\/www.cdc.gov\/antimicrobial-resistance\/stories\/partner-estimates.html. 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