{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T22:58:06Z","timestamp":1781564286897,"version":"3.54.5"},"posted":{"date-parts":[[2023,5,30]]},"group-title":"Microbiology","reference-count":78,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,5,30]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Antagonistic behaviors between bacterial cells can have profound effects on microbial populations and disease outcomes. Polymicrobial interactions may be mediated by contact-dependent proteins with antibacterial properties. The Type VI Secretion System (T6SS) is a macromolecular weapon used by Gram-negative bacteria to translocate proteins into adjacent cells. The T6SS is used by pathogens to escape immune cells, eliminate commensal bacteria, and facilitate infection.\n                  <jats:italic>Stenotrophomonas maltophilia<\/jats:italic>\n                  is a Gram-negative opportunistic pathogen that causes a wide range of infections in immunocompromised patients and infects the lungs of patients with cystic fibrosis. Infections with the bacterium can be deadly and are challenging to treat because many isolates are multidrug-resistant. We found that globally dispersed\n                  <jats:italic>S. maltophilia<\/jats:italic>\n                  clinical and environmental strains possess T6SS genes. We demonstrate that the T6SS of an\n                  <jats:italic>S. maltophilia<\/jats:italic>\n                  patient isolate is active and can eliminate other bacteria. Furthermore, we provide evidence that the T6SS contributes to the competitive fitness of\n                  <jats:italic>S. maltophilia<\/jats:italic>\n                  against a co-infecting\n                  <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                  isolate, and that the T6SS alters the cellular organization of\n                  <jats:italic>S. maltophilia<\/jats:italic>\n                  and\n                  <jats:italic>P. aeruginosa<\/jats:italic>\n                  co-cultures. This study expands our knowledge of the mechanisms employed by\n                  <jats:italic>S. maltophilia<\/jats:italic>\n                  to secrete antibacterial proteins and compete against other bacteria.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>IMPORTANCE<\/jats:title>\n                  <jats:p>\n                    Infections with the opportunistic pathogen\n                    <jats:italic>Stenotrophomonas maltophilia<\/jats:italic>\n                    can be fatal for immunocompromised patients. The mechanisms used by the bacterium to compete against other prokaryotes are not well understood. We found that the T6SS allows\n                    <jats:italic>S. maltophilia<\/jats:italic>\n                    to eliminate other bacteria and contributes to the competitive fitness against a co-infecting isolate. The presence of T6SS genes in isolates across the globe highlights the importance of this apparatus as a weapon in the antibacterial arsenal of\n                    <jats:italic>S. maltophilia<\/jats:italic>\n                    . The T6SS may confer survival advantages to\n                    <jats:italic>S. maltophilia<\/jats:italic>\n                    isolates in polymicrobial communities in both environmental settings and during infections.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2023.05.30.542968","type":"posted-content","created":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T01:30:16Z","timestamp":1685496616000},"source":"Crossref","is-referenced-by-count":1,"title":["The Type VI Secretion System of the Emerging Pathogen\n                  <i>Stenotrophomonas maltophilia<\/i>\n                  has Antibacterial Properties"],"prefix":"10.64898","author":[{"given":"Cristian V.","family":"Crisan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7284-0103","authenticated-orcid":false,"given":"Daria","family":"Van Tyne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5285-5188","authenticated-orcid":false,"given":"Joanna B.","family":"Goldberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2023060303051080000_2023.05.30.542968v1.1","doi-asserted-by":"crossref","unstructured":"Khanum I , Ilyas A , Ali F . 2020. Stenotrophomonas maltophilia meningitis - A case series and review of the literature. 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Antibiotic resistance in the opportunistic pathogen Stenotrophomonas maltophilia . Front Microbiol 6.","DOI":"10.3389\/fmicb.2015.00658"},{"key":"2023060303051080000_2023.05.30.542968v1.6","doi-asserted-by":"crossref","unstructured":"Brooke JS . 2021. Advances in the microbiology of Stenotrophomonas maltophilia . Clin Microbiol Rev 34.","DOI":"10.1128\/CMR.00030-19"},{"key":"2023060303051080000_2023.05.30.542968v1.7","doi-asserted-by":"crossref","first-page":"4171","DOI":"10.1016\/j.ygeno.2020.06.049","article-title":"Genomic insights into evolution of extensive drug resistance in Stenotrophomonas maltophilia complex","volume":"112","year":"2020","journal-title":"Genomics"},{"key":"2023060303051080000_2023.05.30.542968v1.8","doi-asserted-by":"crossref","unstructured":"Cai B , Tillotson G , Benjumea D , Callahan P , Echols R . 2020. The burden of bloodstream infections due to Stenotrophomonas maltophilia in the United States: A large, retrospective database study. 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