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This study investigates interbacterial competition between bacteria found in the oral cavity, where\n                      <jats:italic toggle=\"yes\">Streptococcus<\/jats:italic>\n                      species comprise a large portion of the resident oral microbiota, and\n                      <jats:italic toggle=\"yes\">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 toggle=\"yes\">E. faecalis<\/jats:italic>\n                      compete with each other. Our experiments revealed that multiple strains of\n                      <jats:italic toggle=\"yes\">Streptococcus mutans<\/jats:italic>\n                      , an important cariogenic bacterium, reduce the viability of vancomycin-resistant\n                      <jats:italic toggle=\"yes\">Enterococcus<\/jats:italic>\n                      and other gram-positive bacteria, including\n                      <jats:italic toggle=\"yes\">Staphylococcus epidermidis<\/jats:italic>\n                      and methicillin-resistant\n                      <jats:italic toggle=\"yes\">Staphylococcus aureus<\/jats:italic>\n                      . Furthermore, reduction in viability of bacteria by some strains of\n                      <jats:italic toggle=\"yes\">S. mutans<\/jats:italic>\n                      requires the production of the non-ribosomal cyclic lipopeptide mutanobactin, while another strain inhibits independently of mutanobactin. We determined that\n                      <jats:italic toggle=\"yes\">S. mutans<\/jats:italic>\n                      mutanobactin production increases target cell membrane permeability and that reduction of target cell viability is contact dependent. We also determined that the secreted\n                      <jats:italic toggle=\"yes\">E. faecalis<\/jats:italic>\n                      protease gelatinase (GelE) is required for recovery from mutanobactin-mediated reduction in viability. Additionally, our data show that\n                      <jats:italic toggle=\"yes\">S. mutans<\/jats:italic>\n                      mutanobactin production prevents\n                      <jats:italic toggle=\"yes\">E. faecalis<\/jats:italic>\n                      biofilm formation and kills biofilm-associated\n                      <jats:italic toggle=\"yes\">E. faecalis<\/jats:italic>\n                      . 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 toggle=\"yes\">Enterococcus faecalis<\/jats:italic>\n                        , a common cause of root canal infections. We demonstrate antibacterial activity of streptococcal mutanobactin against gram-positive pathogens, including antibiotic-resistant isolates. We further show that the\n                        <jats:italic toggle=\"yes\">E. faecalis<\/jats:italic>\n                        virulence factor gelatinase promotes recovery from mutanobactin-mediated reduction in viability, and that mutanobactin prevents and kills\n                        <jats:italic toggle=\"yes\">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>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.01623-26","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:01:01Z","timestamp":1791291661000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Streptococcal mutanobactin mediates interspecies competition with gram-positive bacteria"],"prefix":"10.1128","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5415-940X","authenticated-orcid":true,"given":"Ruth Y.","family":"Isenberg","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/017zqws13","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, University of Minnesota Medical School","place":["Minneapolis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2404-1095","authenticated-orcid":true,"given":"Celine W.","family":"Sackih","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/017zqws13","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, University of Minnesota Medical School","place":["Minneapolis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9175-5374","authenticated-orcid":true,"given":"Fatimah A.","family":"Abdulrahman","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/017zqws13","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, University of Minnesota Medical School","place":["Minneapolis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0524-8289","authenticated-orcid":true,"given":"Julia L. 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