{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T11:41:18Z","timestamp":1791805278951,"version":"4.3.4"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,4,16]],"date-time":"2021-04-16T00:00:00Z","timestamp":1618531200000},"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","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:p>Attachment and specific binding to the receptor on the host cell surface is the first step in the process of bacteriophage infection. The lytic phage VP2 is used in phage subtyping of the <jats:italic>Vibrio cholerae<\/jats:italic> biotype El Tor of the O1 serogroup; however, its infection mechanism is poorly understood. In this study, we aimed to identify its receptor on <jats:italic>V. cholerae<\/jats:italic>. The outer membrane protein EpsD in the type II secretory system (T2SS) was found to be related to VP2-specific adsorption to <jats:italic>V. cholerae<\/jats:italic>, and the T2SS inner membrane protein EpsM had a role in successful VP2 infection, although it was not related to adsorption of VP2. The tail fiber protein gp20 of VP2 directly interacts with EpsD. Therefore, we found that in <jats:italic>V. cholerae<\/jats:italic>, in addition to the roles of the T2SS as the transport apparatus of cholera toxin secretion and filamentous phage release, the T2SS is also used as the receptor for phage infection and probably as the channel for phage DNA injection. Our study expands the understanding of the roles of the T2SS in bacteria.<\/jats:p>","DOI":"10.3389\/fcimb.2021.662344","type":"journal-article","created":{"date-parts":[[2021,4,16]],"date-time":"2021-04-16T17:52:33Z","timestamp":1618595553000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["The Type II Secretory System Mediates Phage Infection in Vibrio cholerae"],"prefix":"10.3389","volume":"11","author":[{"given":"Huihui","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenxia","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufeng","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanming","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenpeng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialiang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biao","family":"Kan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,4,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1016\/j.jmb.2004.01.064","article-title":"The crystal structure of the periplasmic domain of the type II secretion system protein EpsM from Vibrio cholerae: the simplest version of the ferredoxin fold","volume":"338","author":"Abendroth","year":"2004","journal-title":"J. Mol. Biol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"fnw002","DOI":"10.1093\/femsle\/fnw002","article-title":"Host receptors for bacteriophage adsorption","volume":"363","author":"Bertozzi Silva","year":"2016","journal-title":"FEMS Microbiol. Lett."},{"key":"B3","doi-asserted-by":"publisher","first-page":"6391","DOI":"10.1128\/iai.68.11.6391-6397.2000","article-title":"Construction of a Vibrio cholerae vaccine candidate using transposon delivery and FLP recombinase-mediated excision","volume":"68","author":"Chiang","year":"2000","journal-title":"Infect. Immun."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00014-17","article-title":"Expanding Role of Type II Secretion in Bacterial Pathogenesis and Beyond","volume":"85","author":"Cianciotto","year":"2017","journal-title":"Infect. Immun."},{"key":"B5","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1126\/science.288.5464.333","article-title":"Convergence of the secretory pathways for cholera toxin and the filamentous phage, CTXphi","volume":"288","author":"Davis","year":"2000","journal-title":"Science"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1111\/j.1462-2920.2007.01545.x","article-title":"Ecology of type II secretion in marine gammaproteobacteria","volume":"10","author":"Evans","year":"2008","journal-title":"Environ. Microbiol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"4000","DOI":"10.1074\/jbc.M117.805689","article-title":"The outer-membrane protein TolC of Vibrio cholerae serves as a second cell-surface receptor for the VP3 phage","volume":"293","author":"Fan","year":"2018","journal-title":"J. Biol. Chem."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.1128\/MMBR.62.4.1301-1314.1998","article-title":"Epidemiology, genetics, and ecology of toxigenic Vibrio cholerae","volume":"62","author":"Faruque","year":"1998","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"B9","doi-asserted-by":"publisher","first-page":"6119","DOI":"10.1073\/pnas.0502069102","article-title":"Self-limiting nature of seasonal cholera epidemics: Role of host-mediated amplification of phage","volume":"102","author":"Faruque","year":"2005","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B10","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1017\/s095026889900254x","article-title":"Phage typing of Campylobacter jejuni and Campylobacter coli and its use as an adjunct to serotyping","volume":"123","author":"Frost","year":"1999","journal-title":"Epidemiol. Infect."},{"key":"B11","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1007\/BF00283883","article-title":"A superfamily of proteins involved in different secretion pathways in gram-negative bacteria: modular structure and specificity of the N-terminal domain","volume":"243","author":"Genin","year":"1994","journal-title":"Mol. Gen. Genet."},{"key":"B12","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1038\/s41564-017-0061-y","article-title":"Pseudomonas aeruginosa defends against phages through type IV pilus glycosylation","volume":"3","author":"Harvey","year":"2018","journal-title":"Nat. Microbiol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/j.coviro.2011.06.009","article-title":"Bacteriophages and their genomes","volume":"1","author":"Hatfull","year":"2011","journal-title":"Curr. Opin. Virol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"e1007731","DOI":"10.1371\/journal.ppat.1007731","article-title":"Structure and assembly of pilotin-dependent and independent secretins of the type II secretion system","volume":"15","author":"Howard","year":"2019","journal-title":"PLoS Pathog."},{"key":"B15","doi-asserted-by":"publisher","first-page":"4652","DOI":"10.1073\/pnas.0600166103","article-title":"Modeling the role of bacteriophage in the control of cholera outbreaks","volume":"103","author":"Jensen","year":"2006","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B16","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1111\/j.1574-6968.2006.00102.x","article-title":"Type II secretion: from structure to function","volume":"255","author":"Johnson","year":"2006","journal-title":"FEMS Microbiol. Lett."},{"key":"B17","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1038\/77305","article-title":"TnAraOut, a transposon-based approach to identify and characterize essential bacterial genes","volume":"18","author":"Judson","year":"2000","journal-title":"Nat. Biotechnol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"5752","DOI":"10.1073\/pnas.95.10.5752","article-title":"A bacterial two-hybrid system based on a reconstituted signal transduction pathway","volume":"95","author":"Karimova","year":"1998","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B19","doi-asserted-by":"publisher","first-page":"2551","DOI":"10.3390\/v6072551","article-title":"Facing antibiotic resistance: Staphylococcus aureus phages as a medical tool","volume":"6","author":"Kazmierczak","year":"2014","journal-title":"Viruses"},{"key":"B20","doi-asserted-by":"publisher","first-page":"5053","DOI":"10.1128\/Aem.01098-08","article-title":"Broad-host-range expression vectors with tightly regulated promoters and their use to examine the influence of TraR and TraM expression on Ti plasmid quorum sensing","volume":"74","author":"Khan","year":"2008","journal-title":"Appl. Environ. Microbiol."},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1128\/ecosalplus.ESP-0034-2018","article-title":"Architecture, Function, and Substrates of the Type II Secretion System","volume":"8","author":"Korotkov","year":"2019","journal-title":"EcoSal. Plus."},{"key":"B22","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1038\/nrmicro2762","article-title":"The type II secretion system: biogenesis, molecular architecture and mechanism","volume":"10","author":"Korotkov","year":"2012","journal-title":"Nat. Rev. Microbiol."},{"key":"B23","doi-asserted-by":"crossref","first-page":"2612","DOI":"10.1016\/S0021-9258(18)69110-0","article-title":"Interaction of Bordetella pertussis adenylate cyclase with calmodulin. Identification of two separated calmodulin-binding domains","volume":"263","author":"Ladant","year":"1988","journal-title":"J.\u00a0Biol. Chem."},{"key":"B24","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/j.celrep.2015.12.038","article-title":"Differential Thiol-Based Switches Jump-Start Vibrio cholerae Pathogenesis","volume":"14","author":"Liu","year":"2016","journal-title":"Cell Rep."},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3390\/v10060338","article-title":"Identification and Characterization of Type IV Pili as the Cellular Receptor of Broad Host Range Stenotrophomonas maltophilia Bacteriophages DLP1 and DLP2","volume":"10","author":"McCutcheon","year":"2018","journal-title":"Viruses"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1006\/plas.1996.0001","article-title":"Conditionally replicative and conjugative plasmids carrying lacZ alpha for cloning, mutagenesis, and allele replacement in bacteria","volume":"35","author":"Metcalf","year":"1996","journal-title":"Plasmid"},{"key":"B27","doi-asserted-by":"publisher","first-page":"145","DOI":"10.33073\/pjm-2010-023","article-title":"Bacteriophage receptors, mechanisms of phage adsorption and penetration into host cell","volume":"59","author":"Rakhuba","year":"2010","journal-title":"Pol. J. Microbiol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1111\/j.1574-6976.2002.tb00605.x","article-title":"Vibrio cholerae and cholera: out of the water and into the host","volume":"26","author":"Reidl","year":"2002","journal-title":"FEMS Microbiol. Rev."},{"key":"B29","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1006\/jmbi.1998.1791","article-title":"Macromolecular assembly and secretion across the bacterial cell envelope: type II protein secretion systems","volume":"279","author":"Russel","year":"1998","journal-title":"J. Mol. Biol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/s0140-6736(03)15328-7","article-title":"Cholera","volume":"363","author":"Sack","year":"2004","journal-title":"Lancet"},{"key":"B31","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1038\/nrmicro3564","article-title":"A century of the phage: past, present and future","volume":"13","author":"Salmond","year":"2015","journal-title":"Nat. Rev. Microbiol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"3523","DOI":"10.1128\/IAI.69.6.3523-3535.2001","article-title":"Type II secretion and pathogenesis","volume":"69","author":"Sandkvist","year":"2001","journal-title":"Infect. Immun."},{"key":"B33","doi-asserted-by":"publisher","first-page":"16555","DOI":"10.1074\/jbc.M110.211078","article-title":"Proteomic analysis of the Vibrio cholerae type II secretome reveals new proteins, including three related serine proteases","volume":"286","author":"Sikora","year":"2011","journal-title":"J. Biol. Chem."},{"key":"B34","doi-asserted-by":"publisher","first-page":"784","DOI":"10.1038\/nbt1183-784","article-title":"A broad host range mobilization system for in vivo genetic engineering: transposon mutagenesis in gramnegative bacteria","volume":"31","author":"Simon","year":"1983","journal-title":"Nat. Biotechnol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1097\/QCO.0000000000000474","article-title":"Cholera: recent updates","volume":"31","author":"Weil","year":"2018","journal-title":"Curr. Opin. Infect. Dis"},{"key":"B36","doi-asserted-by":"publisher","first-page":"2348","DOI":"10.1073\/pnas.1218039110","article-title":"Bile salt-induced intermolecular disulfide bond formation activates Vibrio cholerae virulence","volume":"110","author":"Yang","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.00327","article-title":"Development of a Bacteriophage Cocktail to Constrain the Emergence of Phage-Resistant Pseudomonas aeruginosa","volume":"11","author":"Yang","year":"2020","journal-title":"Front. Microbiol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"2622","DOI":"10.1128\/JB.01370-08","article-title":"The core oligosaccharide and thioredoxin of Vibrio cholerae are necessary for binding and propagation of its typing phage VP3","volume":"191","author":"Zhang","year":"2009","journal-title":"J. Bacteriol."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2021.662344\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T16:02:55Z","timestamp":1619107375000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2021.662344\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,16]]},"references-count":38,"alternative-id":["10.3389\/fcimb.2021.662344"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2021.662344","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,16]]},"article-number":"662344"}}