{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T18:04:29Z","timestamp":1776708269892,"version":"3.51.2"},"reference-count":59,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,12,15]],"date-time":"2016-12-15T00:00:00Z","timestamp":1481760000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,12,15]],"date-time":"2016-12-15T00:00:00Z","timestamp":1481760000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Orally administered phages to control zoonotic pathogens face important challenges, mainly related to the hostile conditions found in the gastrointestinal tract (GIT). These include temperature, salinity and primarily pH, which is exceptionally low in certain compartments. Phage survival under these conditions can be jeopardized and undermine treatment. Strategies like encapsulation have been attempted with relative success, but are typically complex and require several optimization steps. Here we report a simple and efficient alternative, consisting in the genetic engineering of phages to display lipids on their surfaces. <jats:italic>Escherichia coli<\/jats:italic> phage T7 was used as a model and the <jats:italic>E. coli<\/jats:italic> PhoE signal peptide was genetically fused to its major capsid protein (10\u2009A), enabling phospholipid attachment to the phage capsid. The presence of phospholipids on the mutant phages was confirmed by High Performance Thin Layer Chromatography, Dynamic Light Scattering and phospholipase assays. The stability of phages was analysed in simulated GIT conditions, demonstrating improved stability of the mutant phages with survival rates 10<jats:sup>2<\/jats:sup>\u201310<jats:sup>7<\/jats:sup> pfu.mL<jats:sup>\u22121<\/jats:sup> higher than wild-type phages. Our work demonstrates that phage engineering can be a good strategy to improve phage tolerance to GIT conditions, having promising application for oral administration in veterinary medicine.<\/jats:p>","DOI":"10.1038\/srep39235","type":"journal-article","created":{"date-parts":[[2016,12,15]],"date-time":"2016-12-15T13:08:50Z","timestamp":1481807330000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":85,"title":["Genetically manipulated phages with improved pH resistance for oral administration in veterinary medicine"],"prefix":"10.1038","volume":"6","author":[{"given":"Franklin L.","family":"Nobrega","sequence":"first","affiliation":[]},{"given":"Ana Rita","family":"Costa","sequence":"additional","affiliation":[]},{"given":"Jos\u00e9 F.","family":"Santos","sequence":"additional","affiliation":[]},{"given":"Melvin F.","family":"Siliakus","sequence":"additional","affiliation":[]},{"given":"Jan W. M.","family":"van Lent","sequence":"additional","affiliation":[]},{"given":"Serv\u00e9 W. M.","family":"Kengen","sequence":"additional","affiliation":[]},{"given":"Joana","family":"Azeredo","sequence":"additional","affiliation":[]},{"given":"Leon D.","family":"Kluskens","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2016,12,15]]},"reference":[{"key":"BFsrep39235_CR1","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.tibtech.2006.03.003","volume":"24","author":"J Clark","year":"2006","unstructured":"Clark, J. & March, J. Bacteriophages and biotechnology: vaccines, gene therapy and antibacterials. Trends. Biotechnol. 24, 212\u2013218 (2006).","journal-title":"Trends. Biotechnol."},{"key":"BFsrep39235_CR2","unstructured":"Sulakvelidze, A. & Barrow, P. Bacteriophages, biology and applications (eds Kutter, E. & Sulakvelidze, A. ) 335\u2013380 (CRC Press, 2005)."},{"key":"BFsrep39235_CR3","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/0923-2508(91)90187-F","volume":"142","author":"A Berchieri Jr","year":"1991","unstructured":"Berchieri, A. Jr, Lovell, M. A. & Barrow, P. A. The activity in the chicken alimentary tract of bacteriophages lytic for Salmonella typhimurium. Res. Microbiol. 142, 541\u2013549 (1991).","journal-title":"Res. Microbiol."},{"key":"BFsrep39235_CR4","doi-asserted-by":"crossref","first-page":"5032","DOI":"10.1128\/AEM.69.8.5032-5036.2003","volume":"69","author":"D Goode","year":"2003","unstructured":"Goode, D., Allen, V. & Barrow, P. Reduction of experimental Salmonella and Campylobacter contamination of chicken skin by application of lytic bacteriophages. Appl. Environ. Microbiol. 69, 5032\u20135036 (2003).","journal-title":"Appl. Environ. Microbiol."},{"key":"BFsrep39235_CR5","doi-asserted-by":"crossref","first-page":"3877","DOI":"10.1128\/AEM.70.7.3877-3883.2004","volume":"70","author":"PL Connerton","year":"2004","unstructured":"Connerton, P. L. et al. Longitudinal study of Campylobacter jejuni bacteriophages and their hosts from broiler chickens. Appl. Environ. Microbiol. 70, 3877\u20133883 (2004).","journal-title":"Appl. Environ. Microbiol."},{"key":"BFsrep39235_CR6","first-page":"2659","volume":"129","author":"HW Smith","year":"1983","unstructured":"Smith, H. W. & Huggins, M. B. Effectiveness of phages in treating experimental Escherichia coli diarrhoea in calves, piglets and lambs. J. Gen. Microbiol. 129, 2659\u20132675 (1983).","journal-title":"J. Gen. Microbiol."},{"key":"BFsrep39235_CR7","first-page":"1111","volume":"133","author":"HW Smith","year":"1987","unstructured":"Smith, H. W., Huggins, M. B. & Shaw, K. M. The control of experimental Escherichia coli diarrhoea in calves by means of bacteriophages. J. Gen. Microbiol. 133, 1111\u20131126 (1987).","journal-title":"J. Gen. Microbiol."},{"key":"BFsrep39235_CR8","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1128\/CDLI.5.3.294-298.1998","volume":"5","author":"P Barrow","year":"1998","unstructured":"Barrow, P., Lovell, M. & Berchieri, A. Use of lytic bacteriophage for control of experimental Escherichia coli septicemia and meningitis in chickens and calves. Clin. Diagn. Lab. Immunol. 5, 294\u2013298 (1998).","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"BFsrep39235_CR9","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1637\/7041","volume":"47","author":"W Huff","year":"2003","unstructured":"Huff, W., Huff, G., Rath, N., Balog, J. & Donoghue, A. Bacteriophage treatment of a severe Escherichia coli respiratory infection in broiler chickens. Avian. Dis. 47, 1399\u20131405 (2003).","journal-title":"Avian. Dis."},{"key":"BFsrep39235_CR10","doi-asserted-by":"crossref","first-page":"6554","DOI":"10.1128\/AEM.71.11.6554-6563.2005","volume":"71","author":"C Loc Carrillo","year":"2005","unstructured":"Loc Carrillo, C. et al. Bacteriophage therapy to reduce Campylobacter jejuni colonization of broiler chickens. Appl. Environ. Microbiol. 71, 6554\u20136563 (2005).","journal-title":"Appl. Environ. Microbiol."},{"key":"BFsrep39235_CR11","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1186\/1471-2180-10-232","volume":"10","author":"C Carvalho","year":"2010","unstructured":"Carvalho, C. et al. The in vivo efficacy of two administration routes of a phage cocktail to reduce numbers of Campylobacter coli and Campylobacter jejuni in chickens. BMC Microbiology 10, 232 (2010).","journal-title":"BMC Microbiology"},{"key":"BFsrep39235_CR12","doi-asserted-by":"crossref","first-page":"4543","DOI":"10.1128\/AEM.00049-07","volume":"73","author":"RJ Atterbury","year":"2007","unstructured":"Atterbury, R. J. et al. Bacteriophage therapy to reduce Salmonella colonization of broiler chickens. Appl. Environ. Microbiol. 73, 4543\u20134549 (2007).","journal-title":"Appl. Environ. Microbiol."},{"key":"BFsrep39235_CR13","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.ijfoodmicro.2011.08.015","volume":"151","author":"SPT Hooton","year":"2011","unstructured":"Hooton, S. P. T., Atterbury, R. J. & Connerton, I. F. Application of a bacteriophage cocktail to reduce Salmonella Typhimurium U288 contamination on pig skin. Int. J. Food Microbiol. 151, 157\u2013163 (2011).","journal-title":"Int. J. Food Microbiol."},{"key":"BFsrep39235_CR14","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1637\/8953-060509-Reg.1","volume":"54","author":"R Miller","year":"2010","unstructured":"Miller, R., Skinner, E., Sulakvelidze, A., Mathis, G. & Hofacre, C. Bacteriophage therapy for control of necrotic enteritis of broiler chickens experimentally infected with Clostridium perfringens. Avian. Dis. 54, 33\u201340 (2010).","journal-title":"Avian. Dis."},{"key":"BFsrep39235_CR15","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.vetmic.2010.05.014","volume":"146","author":"C Hawkins","year":"2010","unstructured":"Hawkins, C., Harper, D., Burch, D., \u00c4ngg\u00e5rd, E. & Soothill, J. Topical treatment of Pseudomonas aeruginosa otitis of dogs with a bacteriophage mixture: A before\/after clinical trial. Vet. Microbiol. 146, 309\u2013313 (2010).","journal-title":"Vet. Microbiol."},{"key":"BFsrep39235_CR16","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1093\/ps\/82.4.640","volume":"82","author":"R Joerger","year":"2003","unstructured":"Joerger, R. Alternatives to antibiotics: bacteriocins, antimicrobial peptides and bacteriophages. Poul. Sci. 82, 640\u2013647 (2003).","journal-title":"Poul. Sci"},{"key":"BFsrep39235_CR17","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/s12223-011-0039-8","volume":"56","author":"E Jo\u0144czyk","year":"2011","unstructured":"Jo\u0144czyk, E., K\u0142ak, M., Mi\u0119dzybrodzki, R. & G\u00f3rski, A. The influence of external factors on bacteriophages - review. Folia. Microbiol. 56, 191\u2013200 (2011).","journal-title":"Folia. Microbiol."},{"key":"BFsrep39235_CR18","first-page":"35","volume":"38","author":"HW Ackermann","year":"2004","unstructured":"Ackermann, H. W., Tremblay, D. & Moineau, S. Long-term bacteriophage preservation. WFCC Newslett. 38, 35\u201340 (2004).","journal-title":"WFCC Newslett"},{"key":"BFsrep39235_CR19","doi-asserted-by":"crossref","first-page":"3019","DOI":"10.3168\/jds.2008-1744","volume":"92","author":"P Garc\u00eda","year":"2009","unstructured":"Garc\u00eda, P., Madera, C., Mart\u00ednez, B., Rodr\u00edguez, A. & Evaristo Su\u00e1rez, J. Prevalence of bacteriophages infecting Staphylococcus aureus in dairy samples and their potential as biocontrol agents. J. Dairy Sci. 92, 3019\u20133026 (2009).","journal-title":"J. Dairy Sci."},{"key":"BFsrep39235_CR20","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1128\/AAC.00635-06","volume":"51","author":"R Watanabe","year":"2007","unstructured":"Watanabe, R. et al. Efficacy of bacteriophage therapy against gut-derived sepsis caused by Pseudomonas aeruginosa in mice. Antimicrob. Agents Chemother. 51, 446\u2013452 (2007).","journal-title":"Antimicrob. Agents Chemother."},{"key":"BFsrep39235_CR21","doi-asserted-by":"crossref","first-page":"51","DOI":"10.3389\/fmicb.2014.00051","volume":"5","author":"M Ly-Chatain","year":"2014","unstructured":"Ly-Chatain, M. The factors affecting effectiveness of treatment in phages therapy. Front. Microbiol. 5, 51 (2014).","journal-title":"Front. Microbiol."},{"key":"BFsrep39235_CR22","doi-asserted-by":"crossref","first-page":"2558","DOI":"10.1128\/AAC.48.7.2558-2569.2004","volume":"48","author":"S Chibani-Chennoufi","year":"2004","unstructured":"Chibani-Chennoufi, S. et al. In vitro and in vivo bacteriolytic activities of Escherichia coli phages: Implications for phage therapy. Antimicrob. Agents Chemother. 48, 2558\u20132569 (2004).","journal-title":"Antimicrob. Agents Chemother."},{"key":"BFsrep39235_CR23","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.jviromet.2004.08.010","volume":"122","author":"MR Olson","year":"2004","unstructured":"Olson, M. R., Axler, R. P. & Hicks, R. E. Effects of freezing and storage temperature on MS2 viability. J. Virol. Methods 122, 147\u2013152 (2004).","journal-title":"J. Virol. Methods"},{"key":"BFsrep39235_CR24","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1128\/aem.40.6.1067-1079.1980","volume":"40","author":"CJ Hurst","year":"1980","unstructured":"Hurst, C. J., Gerba, C. P. & Cech, I. Effects of environmental variables and soil characteristics on virus survival in soil. Appl. Environ. Microbiol. 40, 1067\u20131079 (1980).","journal-title":"Appl. Environ. Microbiol."},{"key":"BFsrep39235_CR25","doi-asserted-by":"crossref","first-page":"1748","DOI":"10.1016\/S0043-1354(98)00380-7","volume":"33","author":"AM Nasser","year":"1999","unstructured":"Nasser, A. M. & Oman, S. D. Quantitative assessment of the inactivation of pathogenic and indicator viruses in natural water sources. Water Res. 33, 1748\u20131752 (1999).","journal-title":"Water Res."},{"key":"BFsrep39235_CR26","first-page":"268","volume":"8","author":"B Tey","year":"2009","unstructured":"Tey, B. et al. Production of fusion m13 phage bearing the disulphide constrained peptide sequence (C-WSFFSNI-C) that interacts with hepatitis B core antigen. J. African Biotechnol. 8, 268\u2013273 (2009).","journal-title":"Biotechnol."},{"key":"BFsrep39235_CR27","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1002\/mabi.201200109","volume":"12","author":"C Dini","year":"2012","unstructured":"Dini, C., Islan, G. A., de Urraza, P. J. & Castro, G. R. Novel biopolymer matrices for microencapsulation of phages: enhanced protection against acidity and protease activity. Macromol. Biosci. 12, 1200\u20131208 (2012).","journal-title":"Macromol. Biosci."},{"key":"BFsrep39235_CR28","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1021\/bm049607o","volume":"6","author":"A Metters","year":"2004","unstructured":"Metters, A. & Hubbell, J. Network formation and degradation behavior of hydrogels formed by michael-type addition reactions. Biomacromolecules 6, 290\u2013301 (2004).","journal-title":"Biomacromolecules"},{"key":"BFsrep39235_CR29","unstructured":"Bosio, V., Islan, G., Mart\u00ednez, Y. & Castro, G. Advances in Bioprocesses in Food Industries (eds Soccol, C. R., Pandey, A., Soccol, V. T. & Laroche, C. ) 1 (Asiatech Press, 2011)."},{"key":"BFsrep39235_CR30","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1021\/mp060100x","volume":"4","author":"GR Castro","year":"2007","unstructured":"Castro, G. R., Panilaitis, B., Bora, E. & Kaplan, D. L. Controlled release biopolymers for enhancing the immune response. Mol. Pharm. 4, 33\u201346 (2007).","journal-title":"Mol. Pharm."},{"key":"BFsrep39235_CR31","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.lwt.2015.12.039","volume":"68","author":"M Samtlebe","year":"2016","unstructured":"Samtlebe, M. et al. Carrier systems for bacteriophages to supplement food systems: Encapsulation and controlled release to modulate the human gut microbiota. LWT - Food Sci. Technol. 68, 334\u2013340 (2016).","journal-title":"LWT - Food Sci. Technol"},{"key":"BFsrep39235_CR32","doi-asserted-by":"crossref","first-page":"4799","DOI":"10.1128\/AEM.00246-08","volume":"74","author":"Y Ma","year":"2008","unstructured":"Ma, Y. et al. Microencapsulation of bacteriophage Felix O1 into chitosan-alginate microspheres for oral delivery. Appl. Environ. Microbiol. 74, 4799\u20134805 (2008).","journal-title":"Appl. Environ. Microbiol."},{"key":"BFsrep39235_CR33","doi-asserted-by":"crossref","first-page":"4841","DOI":"10.1128\/AEM.00812-15","volume":"81","author":"J Colom","year":"2015","unstructured":"Colom, J. et al. Liposome-encapsulated bacteriophages for enhanced oral phage therapy against Salmonella spp. Appl. Environ. Microbiol. 81, 4841\u20134849 (2015).","journal-title":"Appl. Environ. Microbiol."},{"key":"BFsrep39235_CR34","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/S0168-3659(00)00294-7","volume":"68","author":"C Sturesson","year":"2000","unstructured":"Sturesson, C. & Degling Wikingsson, L. Comparison of poly(acryl starch) and poly(lactide-co-glycolide) microspheres as drug delivery system for a rotavirus vaccine. J. Control. Release 68, 441\u2013450 (2000).","journal-title":"J. Control. Release"},{"key":"BFsrep39235_CR35","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1002\/mabi.200300126","volume":"4","author":"E Chiellini","year":"2004","unstructured":"Chiellini, E., Cinelli, P., Chiellini, F. & Imam, S. H. Environmentally degradable bio-based polymeric blends and composites. Macromol. Biosci. 4, 218\u2013231 (2004).","journal-title":"Macromol. Biosci."},{"key":"BFsrep39235_CR36","doi-asserted-by":"crossref","first-page":"5","DOI":"10.4161\/bact.18778","volume":"2","author":"L Marinelli","year":"2012","unstructured":"Marinelli, L., Hatfull, G. & Piuri, M. Recombineering: A powerful tool for modification of bacteriophage genomes. Bacteriophage 2, 5\u201314 (2012).","journal-title":"Bacteriophage"},{"key":"BFsrep39235_CR37","doi-asserted-by":"crossref","first-page":"e3957","DOI":"10.1371\/journal.pone.0003957","volume":"3","author":"LJ Marinelli","year":"2008","unstructured":"Marinelli, L. J. et al. BRED: A simple and powerful tool for constructing mutant and recombinant bacteriophage genomes. PLoS One 3, e3957 (2008).","journal-title":"PLoS One"},{"key":"BFsrep39235_CR38","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/newbio239117a0","volume":"239","author":"C Milstein","year":"1972","unstructured":"Milstein, C., Brownlee, G., TM, H. & Mathews, M. A possible precursor of immunoglobulin light chains. Nature New Biol. 239, 117\u2013120 (1972).","journal-title":"Nature New Biol"},{"key":"BFsrep39235_CR39","first-page":"55","volume":"1694","author":"SJ Facey","year":"2004","unstructured":"Facey, S. J. & Kuhn, A. Membrane integration of E. coli model membrane proteins. BBA - Mol. Cell Res. 1694, 55\u201366 (2004).","journal-title":"BBA - Mol. Cell Res"},{"key":"BFsrep39235_CR40","doi-asserted-by":"crossref","first-page":"5145","DOI":"10.1093\/nar\/12.13.5145","volume":"12","author":"ME Watson","year":"1984","unstructured":"Watson, M. E. Compilation of published signal sequences. Nucleic Acids Res. 12, 5145\u20135164 (1984).","journal-title":"Nucleic Acids Res"},{"key":"BFsrep39235_CR41","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/0022-2836(85)90046-4","volume":"184","author":"G von Heijne","year":"1985","unstructured":"von Heijne, G. Signal sequences. J. Mol. Biol. 184, 99\u2013105 (1985).","journal-title":"J. Mol. Biol."},{"key":"BFsrep39235_CR42","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.1021\/bi00121a014","volume":"31","author":"RCA Keller","year":"1992","unstructured":"Keller, R. C. A., Killian, J. A. & De Kruijff, B. Anionic phospholipids are essential for alpha-helix formation of the signal peptide of prePhoE upon interaction with phospholipid vesicles. Biochemistry 31, 1672\u20131677 (1992).","journal-title":"Biochemistry"},{"key":"BFsrep39235_CR43","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1126\/science.2941862","volume":"233","author":"M Briggs","year":"1986","unstructured":"Briggs, M., Cronell, D., Dluhy, R. & Gierasch, L. Conformations of signal peptides induced by lipids suggest initial steps in protein export. Science 233, 206\u2013208 (1986).","journal-title":"Science"},{"key":"BFsrep39235_CR44","doi-asserted-by":"crossref","first-page":"8131","DOI":"10.1021\/bi00487a021","volume":"29","author":"J Killian","year":"1990","unstructured":"Killian, J. et al. Tryptophan fluorescence study on the interaction of the signal peptide of the Escherichia coli outer membrane protein PhoE with model membranes. Biochemistry 29, 8131\u20138137 (1990).","journal-title":"Biochemistry"},{"key":"BFsrep39235_CR45","doi-asserted-by":"crossref","first-page":"6241","DOI":"10.1021\/bi00239a023","volume":"30","author":"C McKnight","year":"1991","unstructured":"McKnight, C., Rafalski, M. & Gierasch, L. Fluorescence analysis of tryptophan-containing variants of the LamB signal sequence upon insertion into a lipid bilayer. Biochemistry 30, 6241\u20136246 (1991).","journal-title":"Biochemistry"},{"key":"BFsrep39235_CR46","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1017\/S1466252308001576","volume":"9","author":"RP Johnson","year":"2008","unstructured":"Johnson, R. P. et al. Bacteriophages for prophylaxis and therapy in cattle, poultry and pigs. Anim. Health Res. Rev. 9, 201\u2013215 (2008).","journal-title":"Anim. Health Res. Rev."},{"key":"BFsrep39235_CR47","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.mib.2011.07.010","volume":"14","author":"A Bertin","year":"2011","unstructured":"Bertin, A., de Frutos, M. & Letellier, L. Bacteriophage-host interactions leading to genome internalization. Curr. Opin. Microbiol. 14, 492\u2013496 (2011).","journal-title":"Curr. Opin. Microbiol."},{"key":"BFsrep39235_CR48","doi-asserted-by":"crossref","first-page":"G526","DOI":"10.1152\/ajpgi.2001.281.2.G526","volume":"281","author":"JP Li","year":"2001","unstructured":"Li, J. P., Chang, T.-M., Wagner, D. & Chey, W. Y. Pancreatic phospholipase A2 from the small intestine is a secretin-releasing factor in rats. Am. J. Physiol. Gastrointest. Liver Physiol. 281, G526\u2013G532 (2001).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"BFsrep39235_CR49","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1007\/s13228-011-0015-4","volume":"2","author":"EK Ulleberg","year":"2011","unstructured":"Ulleberg, E. K. et al. Human gastrointestinal juices intended for use in in vitro digestion models. Food Dig. 2, 52\u201361 (2011).","journal-title":"Food Dig"},{"key":"BFsrep39235_CR50","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.4315\/0362-028X-63.12.1665","volume":"63","author":"J Koo","year":"2000","unstructured":"Koo, J., DePaola, A. & Marshall, D. L. Effect of simulated gastric fluid and bile on survival of Vibrio vulnificus and Vibrio vulnificus phage. J. Food Prot. 63, 1665\u20131669 (2000).","journal-title":"J. Food Prot."},{"key":"BFsrep39235_CR51","doi-asserted-by":"crossref","unstructured":"Khanorkar, S. Insights in Physiology. 170\u2013177 (Jaypee Brothers Medical Publishers, 2012).","DOI":"10.5005\/jp\/books\/11552_29"},{"key":"BFsrep39235_CR52","doi-asserted-by":"crossref","first-page":"6998","DOI":"10.1128\/jb.173.21.6998-7003.1991","volume":"173","author":"BG Condron","year":"1991","unstructured":"Condron, B. G., Atkins, J. F. & Gesteland, R. F. Frameshifting in gene 10 of bacteriophage T7. J. Bacteriol. 173, 6998\u20137003 (1991).","journal-title":"J. Bacteriol."},{"key":"BFsrep39235_CR53","doi-asserted-by":"crossref","unstructured":"Barr, J. J. et al. Subdiffusive motion of bacteriophage in mucosal surfaces increases the frequency of bacterial encounters. Proc. Natl. Acad. Sci. 112 (2015).","DOI":"10.1073\/pnas.1508355112"},{"key":"BFsrep39235_CR54","unstructured":"Sambrook, J., Fritch, E. F. & Maniatis, T. Molecular cloning. A laboratory manual (Cold Spring Harbor Laboratory Press, 1987)."},{"key":"BFsrep39235_CR55","unstructured":"Ausubel, F. et al. Short Protocols in Molecular Biology, 5th ed (eds Ausubel, F. M. et al.) (John Wiley & Sons, 2002)."},{"key":"BFsrep39235_CR56","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1139\/y59-099","volume":"37","author":"EG Bligh","year":"1959","unstructured":"Bligh, E. G. & Dyer, W. J. A rapid method of total lipid extraction and purification. Can. J. Biochem. Physiol. 37, 911\u2013917 (1959).","journal-title":"Can. J. Biochem. Physiol."},{"key":"BFsrep39235_CR57","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1085\/jgp.22.3.365","volume":"22","author":"EL Ellis","year":"1939","unstructured":"Ellis, E. L. & Delbr\u00fcck, M. The growth of bacteriophage. J. Gen. Physiol. 22, 365\u2013384 (1939).","journal-title":"J. Gen. Physiol."},{"key":"BFsrep39235_CR58","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1002\/path.1700890112","volume":"89","author":"HW Smith","year":"1965","unstructured":"Smith, H. W. Observations on the flora of the alimentary tract of animals and factors affecting its composition. J. Pathol. Bacteriol. 89, 95\u2013122 (1965).","journal-title":"J. Pathol. Bacteriol."},{"key":"BFsrep39235_CR59","doi-asserted-by":"crossref","unstructured":"Kropinski, A., Mazzocco, A., Waddell, T., Lingohr, E. & Johnson, R. In Bacteriophages Vol. 501 Methods in Molecular Biology (eds Clokie, M. R. J. & Kropinski, A. M. ) 69\u201376 (Humana Press, 2009).","DOI":"10.1007\/978-1-60327-164-6_7"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep39235.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep39235","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep39235.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T02:52:13Z","timestamp":1672887133000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep39235"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,12,15]]},"references-count":59,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,12,23]]}},"alternative-id":["BFsrep39235"],"URL":"https:\/\/doi.org\/10.1038\/srep39235","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,12,15]]},"assertion":[{"value":"2 September 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 November 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 December 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"39235"}}