{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T02:48:14Z","timestamp":1788058094592,"version":"build-2784847793"},"reference-count":72,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFD1800904"],"award-info":[{"award-number":["2022YFD1800904"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p><jats:italic>Streptococcus suis<\/jats:italic> poses a significant threat to both pig farming and public health, causing severe disease such as septicemia and meningitis. The type VII secretion system (T7SS) delivers toxic effectors to play a crucial role in interbacterial competition and is vital for the zoonotic pathogen <jats:italic>S. suis<\/jats:italic> to colonize host tonsils effectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Here, we identified a type of hypothetical T7SS effector in <jats:italic>S. suis<\/jats:italic>, which appears to be fragmented toxins lacking the N-terminal YeeF domain, redesignated as MSE-ExTs. MSE (marker for searching effectors) is a conserved sequence at the N-termini of modular effectors showing a diverse range of toxicities targeting NAD +. Cognate WXG100-like and full-length EssC proteins contribute to activate the T7SS secretion. While most MSE-ExTs (MSE-fusing exported toxins) are encoded downstream of a truncated essC and lack cognate WXG100-like genes, they are nonetheless exported and function in interbacterial antagonism, thereby conferring a competitive advantage against bacterial isolates derived from tonsil microbiota. Deletion of the truncated essC could not diminish the MSE-ExT1 delivery, while the full-length EssC1 encoded in T7SS core locus was required for the lethality of MSE-ExT1 to sensitive bacterial cells. MapC2, an upstream small helical protein, shares a nearly identical C-terminal 50-amino acid (aa) sequence with EIC-CR (C-terminal conserved region of effector-paired immunity protein). This conserved fragment harbors a \u201cYxxxD\u201d targeting signal and interacts with the D1 ATPase domain of the non-neighboring EssC, thereby activating the secretion of MSE-ExTs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This alternative strategy facilitates effectors\u2019 delivery, even for fragmented substrates, highlighting its importance in ensuring the functionality of T7SS.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2025.1685307","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T07:45:18Z","timestamp":1760427918000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Identifying a type of toxic effectors exported by the type VII secretion system to enhance competitive fitness in Streptococcus suis"],"prefix":"10.3389","volume":"15","author":[{"given":"Qiankun","family":"Bai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinming","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongfu","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiale","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1038\/nrmicro1773","article-title":"Type VII secretion\u2013mycobacteria show the way","volume":"5","author":"Abdallah","year":"2007","journal-title":"Nat. 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