{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:06:53Z","timestamp":1768522013491,"version":"3.49.0"},"reference-count":51,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T00:00:00Z","timestamp":1690416000000},"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":["2021YFC2300304"],"award-info":[{"award-number":["2021YFC2300304"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["19008022271"],"award-info":[{"award-number":["19008022271"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Research Foundation for Youth Scholars of the Beijing Technology and Business University","award":["2021YFC2300304"],"award-info":[{"award-number":["2021YFC2300304"]}]},{"name":"Research Foundation for Youth Scholars of the Beijing Technology and Business University","award":["19008022271"],"award-info":[{"award-number":["19008022271"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Cholera, caused by pathogenic Vibrio cholerae, poses a significant public health risk through water and food transmission. Biofilm-associated V. cholerae plays a crucial role in seasonal cholera outbreaks as both a reservoir in aquatic environments and a direct source of human infection. Although VP3, a lytic phage, shows promise in eliminating planktonic V. cholerae from the aquatic environment, its effectiveness against biofilm-associated V. cholerae is limited. To address this limitation, our proposed approach aims to enhance the efficacy of VP3 in eliminating biofilm-associated V. cholerae by augmenting the availability of phage receptors on the surface of Vibrio cholerae. TolC is a receptor of VP3 and a salt efflux pump present in many bacteria. In this study, we employed NaCl as an enhancer to stimulate TolC expression and observed a significant enhancement of TolC expression in both planktonic and biofilm cells of V. cholerae. This enhancement led to improved adsorption of VP3. Importantly, our findings provide strong evidence that high salt concentrations combined with VP3 significantly improve the elimination of biofilm-associated V. cholerae. This approach offers a potential strategy to eliminate biofilm-formation bacteria by enhancing phage\u2013host interaction.<\/jats:p>","DOI":"10.3390\/v15081639","type":"journal-article","created":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T01:56:16Z","timestamp":1690509376000},"page":"1639","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["VP3 Phage Combined with High Salt Promotes the Lysis of Biofilm-Associated Vibrio cholerae"],"prefix":"10.3390","volume":"15","author":[{"given":"Xu","family":"Li","sequence":"first","affiliation":[{"name":"School of Light Industry, Beijing Technology and Business University, Beijing 100048, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaorui","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huayao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Biao","family":"Kan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fenxia","family":"Fan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"375","DOI":"10.3389\/fmicb.2013.00375","article-title":"Environmental reservoirs and mechanisms of persistence of Vibrio cholerae","volume":"4","author":"Lutz","year":"2013","journal-title":"Front. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/mSphereDirect.00238-18","article-title":"Genes Activated by Vibrio cholerae upon Exposure to Caenorhabditis elegans Reveal the Mannose-Sensitive Hemagglutinin to Be Essential for Colonization","volume":"3","author":"List","year":"2018","journal-title":"mSphere"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/978-3-031-22997-8_2","article-title":"New Insights into Vibrio cholerae Biofilms from Molecular Biophysics to Microbial Ecology","volume":"1404","author":"Tai","year":"2023","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e00483-18","DOI":"10.1128\/mBio.00483-18","article-title":"Biofilms Comprise a Component of the Annual Cycle of Vibrio cholerae in the Bay of Bengal Estuary","volume":"9","author":"Sultana","year":"2018","journal-title":"mBio"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.copbio.2008.04.005","article-title":"Biofilms in water, its role and impact in human disease transmission","volume":"19","author":"Huq","year":"2008","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1038\/1831533a0","article-title":"Enterotoxicity of Bacteria-free Culture-filtrate of Vibrio cholerae","volume":"183","author":"De","year":"1959","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6350","DOI":"10.1073\/pnas.0601277103","article-title":"Transmissibility of cholera: In vivo-formed biofilms and their relationship to infectivity and persistence in the environment","volume":"103","author":"Faruque","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1073\/pnas.0237386100","article-title":"Reduction of cholera in Bangladeshi villages by simple filtration","volume":"100","author":"Colwell","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2508","DOI":"10.1128\/aem.62.7.2508-2512.1996","article-title":"A simple filtration method to remove plankton-associated Vibrio cholerae in raw water supplies in developing countries","volume":"62","author":"Huq","year":"1996","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"204","DOI":"10.3934\/microbiol.2020014","article-title":"An exegesis of bacteriophage therapy: An emerging player in the fight against anti-microbial resistance","volume":"6","author":"Adesanya","year":"2020","journal-title":"AIMS Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.cell.2022.11.017","article-title":"Phage therapy: From biological mechanisms to future directions","volume":"186","author":"Strathdee","year":"2023","journal-title":"Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1073\/pnas.1810138116","article-title":"Niche adaptation limits bacteriophage predation of Vibrio cholerae in a nutrient-poor aquatic environment","volume":"116","author":"Camilli","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1093\/infdis\/jiy563","article-title":"Reviving Phage Therapy for the Treatment of Cholera","volume":"219","author":"Bhandare","year":"2019","journal-title":"J. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Naser, I.B., Hoque, M.M., Abdullah, A., Bari, S.M.N., Ghosh, A.N., and Faruque, S.M. (2017). Environmental bacteriophages active on biofilms and planktonic forms of toxigenic Vibrio cholerae: Potential relevance in cholera epidemiology. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0180838"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2136","DOI":"10.1038\/s41564-019-0579-2","article-title":"Breakdown of Vibrio cholerae biofilm architecture induced by antibiotics disrupts community barrier function","volume":"4","author":"Hartmann","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.mib.2017.09.004","article-title":"Phage therapy as an alternative or complementary strategy to prevent and control biofilm-related infections","volume":"39","author":"Pires","year":"2017","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Ferriol-Gonz\u00e1lez, C., and Domingo-Calap, P. (2020). Phages for Biofilm Removal. Antibiotics, 9.","DOI":"10.3390\/antibiotics9050268"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"145","DOI":"10.7883\/yoken.67.145","article-title":"Cholera outbreaks in South and Southeast Asia: Descriptive analysis, 2003\u20132012","volume":"67","author":"Mahapatra","year":"2014","journal-title":"Jpn. J. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1016\/S0140-6736(22)00330-0","article-title":"Cholera","volume":"399","author":"Kanungo","year":"2022","journal-title":"Lancet"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1016\/S0140-6736(17)30559-7","article-title":"Cholera","volume":"390","author":"Clemens","year":"2017","journal-title":"Lancet"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"A31","DOI":"10.1016\/j.vaccine.2019.07.078","article-title":"Epidemiology of cholera","volume":"38","author":"Deen","year":"2020","journal-title":"Vaccine"},{"key":"ref_22","unstructured":"Disease Control Bureau of the Ministry of Health of China (2013). Manual of Cholera Prevention, People\u2019s Medical Publishing House. [6th ed.]."},{"key":"ref_23","doi-asserted-by":"crossref","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":"ref_24","doi-asserted-by":"crossref","first-page":"40022","DOI":"10.1038\/srep40022","article-title":"Yersinia pestis halotolerance illuminates plague reservoirs","volume":"7","author":"Malek","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3142","DOI":"10.1002\/pmic.200401128","article-title":"Proteomic analysis on the expression of outer membrane proteins of Vibrio alginolyticus at different sodium concentrations","volume":"5","author":"Xu","year":"2005","journal-title":"Proteomics"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1089\/mdr.2018.0079","article-title":"Variability in the Adaptive Response of Antibiotic-Resistant Salmonella Typhimurium to Environmental Stresses","volume":"25","author":"Uddin","year":"2019","journal-title":"Microb. Drug Resist."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1017\/S0022172400043606","article-title":"Further Investigations on the Nature of Ultra-Microscopic Viruses and their Cultivation","volume":"36","author":"Twort","year":"1936","journal-title":"J. Hyg."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/nrmicro821","article-title":"Bacterial biofilms: From the natural environment to infectious diseases","volume":"2","author":"Costerton","year":"2004","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"9521","DOI":"10.3168\/jds.2021-20128","article-title":"Effects of tolC on tolerance to bile salts and biofilm formation in Cronobacter malonaticus","volume":"104","author":"Wang","year":"2021","journal-title":"J. Dairy Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/j.ijantimicag.2018.09.006","article-title":"Bacteriophage Sb-1 enhances antibiotic activity against biofilm, degrades exopolysaccharide matrix and targets persisters of Staphylococcus aureus","volume":"52","author":"Tkhilaishvili","year":"2018","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_31","first-page":"703","article-title":"Synergistic Interaction Between Phage Therapy and Antibiotics Clears Pseudomonas Aeruginosa Infection in Endocarditis and Reduces Virulence","volume":"215","author":"Oechslin","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1099\/00221287-28-2-367","article-title":"Relationship of sodium chloride tolerance and serological group of staphylococcal phages","volume":"28","author":"West","year":"1962","journal-title":"J. Gen. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"268","DOI":"10.3390\/md7030268","article-title":"Phage therapy and photodynamic therapy: Low environmental impact approaches to inactivate microorganisms in fish farming plants","volume":"7","author":"Almeida","year":"2009","journal-title":"Mar. Drugs"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1039\/c0em00434k","article-title":"Evaluating seasonal dynamics of bacterial communities in marine fish aquaculture: A preliminary study before applying phage therapy","volume":"13","author":"Pereira","year":"2011","journal-title":"J. Environ. Monit."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1016\/j.jbiomech.2006.07.027","article-title":"Comparison of long-term numerical and experimental total knee replacement wear during simulated gait loading","volume":"40","author":"Knight","year":"2007","journal-title":"J. Biomech."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"fiz190","DOI":"10.1093\/femsec\/fiz190","article-title":"Salinity reduces bacterial diversity, but increases network complexity in Tibetan Plateau lakes","volume":"95","author":"Ji","year":"2019","journal-title":"FEMS Microbiol. Ecol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1038\/ismej.2011.41","article-title":"Transitions in bacterial communities along the 2000 km salinity gradient of the Baltic Sea","volume":"5","author":"Herlemann","year":"2011","journal-title":"ISME J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1046\/j.1462-2920.2002.00306.x","article-title":"Prokaryotic genetic diversity throughout the salinity gradient of a coastal solar saltern","volume":"4","author":"Benlloch","year":"2002","journal-title":"Environ. Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"25078","DOI":"10.1038\/srep25078","article-title":"Salinity shapes microbial diversity and community structure in surface sediments of the Qinghai-Tibetan Lakes","volume":"6","author":"Yang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3425","DOI":"10.1128\/AEM.70.6.3425-3433.2004","article-title":"Richness and diversity of bacterioplankton species along an estuarine gradient in Moreton Bay, Australia","volume":"70","author":"Hewson","year":"2004","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Wang, J., Yang, D., Zhang, Y., Shen, J., van der Gast, C., Hahn, M.W., and Wu, Q. (2011). Do patterns of bacterial diversity along salinity gradients differ from those observed for macroorganisms?. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0027597"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"6251","DOI":"10.1128\/IAI.70.11.6251-6262.2002","article-title":"Phage therapy of local and systemic disease caused by Vibrio vulnificus in iron-dextran-treated mice","volume":"70","author":"Cerveny","year":"2002","journal-title":"Infect. Immun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1128\/jb.58.5.611-620.1949","article-title":"The Streptococcus lactis host-virus system; characteristics of virus growth and the effect of electrolytes on virus adsorption","volume":"58","author":"Cherry","year":"1949","journal-title":"J. Bacteriol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1084\/jem.97.6.807","article-title":"Virus and cell interaction with ion exchangers","volume":"97","author":"Puck","year":"1953","journal-title":"J. Exp. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/S0168-6496(03)00149-1","article-title":"Salinity as a structuring factor for the composition and performance of bacterioplankton degrading riverine DOC","volume":"45","author":"Langenheder","year":"2003","journal-title":"FEMS Microbiol. Ecol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"5478","DOI":"10.1128\/AEM.00767-06","article-title":"Bacterioplankton community composition along a salinity gradient of sixteen high-mountain lakes located on the Tibetan Plateau, China","volume":"72","author":"Wu","year":"2006","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"7017","DOI":"10.1128\/AEM.01544-09","article-title":"Low taxon richness of bacterioplankton in high-altitude lakes of the eastern tibetan plateau, with a predominance of Bacteroidetes and Synechococcus spp","volume":"75","author":"Xing","year":"2009","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4748","DOI":"10.1128\/AEM.07806-11","article-title":"Influence of salinity on the bacterial community composition in Lake Bosten, a large oligosaline lake in arid northwestern China","volume":"78","author":"Tang","year":"2012","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"282","DOI":"10.3389\/fmicb.2017.00282","article-title":"Fish as Hosts of Vibrio cholerae","volume":"8","author":"Halpern","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e0021121","DOI":"10.1128\/cmr.00211-21","article-title":"Diagnosis, Management, and Future Control of Cholera","volume":"35","author":"Chowdhury","year":"2022","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.watres.2016.12.004","article-title":"The roles of bacteriophages in membrane-based water and wastewater treatment processes: A review","volume":"110","author":"Wu","year":"2017","journal-title":"Water Res."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/8\/1639\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:20:54Z","timestamp":1760127654000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/8\/1639"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,27]]},"references-count":51,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["v15081639"],"URL":"https:\/\/doi.org\/10.3390\/v15081639","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,27]]}}}