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With its erstwhile appellation as the main terminal branch of the general secretory pathway, the T2SS has sometimes been described as (only) secreting a relatively small number of degradative enzymes for the purpose of nutrient acquisition. However, as comprehensively reviewed here, the T2SS is a great deal more than this, e.g., it (i) can secrete and expose on the cell surface over 100 proteins, (ii) is a major mediator of virulence against humans, animals, and plants, secreting diverse substrates that target essentially every step in the pathogenic process, (iii) promotes biofilm formation and environmental reactions such as metal reduction, (iv) has functional interactions with other secretion systems, and (v) has a homolog in mitochondria. Moreover, current assessment of the literature reveals an underappreciated role for the T2SS in both interbacterial antagonism and bacterial competition with fungi, protozoa, and perhaps algae. We also assembled data indicating that the T2SS mediates bacterial resistance to antibiotics. Finally, the T2SS is a fascinatingly complex \u201cmachine\u201d whose contributing parts can vary and whose ability to recognize substrates is primarily conformational, involving spatially separated elements that interact with the T2SS apparatus through transient, multivalent interactions rather than a single dedicated binding motif.<\/jats:p>","DOI":"10.1128\/mmbr.00118-25","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T13:01:31Z","timestamp":1787749291000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Revisiting the type II secretion system: it is more than you might think"],"prefix":"10.1128","volume":"90","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9572-8322","authenticated-orcid":true,"given":"Nicholas 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