{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T16:19:24Z","timestamp":1778775564736,"version":"3.51.4"},"reference-count":65,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,3,10]],"date-time":"2020-03-10T00:00:00Z","timestamp":1583798400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN-2015-04871"],"award-info":[{"award-number":["RGPIN-2015-04871"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008762","name":"Genome Canada","doi-asserted-by":"publisher","award":["8505"],"award-info":[{"award-number":["8505"]}],"id":[{"id":"10.13039\/100008762","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Bacteriophages have shown promise as therapeutic alternatives to antibiotics for the control of infectious bacteria, including the human pathogen Salmonella. However, the development of effective phage-based applications requires the elucidation of key interactions between phages and target hosts, particularly since host resistance to phage is inevitable. Little is known about the alteration of host phenotypes following the development of resistance to phage. The aim of this study is to evaluate the antibiotic susceptibility and virulence of a Salmonella isolate following the development of resistance to bacteriophage SI1. We observed enhanced susceptibility to tetracycline and decreased invasion capacity in a differentiated Caco-2 intestinal cell line. Whole genome sequence analysis revealed an array of mutations, most notably, truncations in vgrG1_2, a core gene involved in Type VI secretion and mutations in the lipopolysaccharide, thereby indicating the plausible attachment site of phage SI1. These findings shed light on understanding the underlying mechanism for phage immunity within the host. Importantly, we reveal an associated genetic cost to the bacterial host with developing resistance to phages. Taken together, these results will aid in advancing strategies to delay or eliminate the development of host resistance when designing informed phage-based antimicrobials.<\/jats:p>","DOI":"10.3390\/ijms21051883","type":"journal-article","created":{"date-parts":[[2020,3,10]],"date-time":"2020-03-10T11:59:36Z","timestamp":1583841576000},"page":"1883","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Bacteriophage-Insensitive Mutants of Antimicrobial-Resistant Salmonella Enterica are Altered in their Tetracycline Resistance and Virulence in Caco-2 Intestinal Cells"],"prefix":"10.3390","volume":"21","author":[{"given":"Karen","family":"Fong","sequence":"first","affiliation":[{"name":"Food, Nutrition and Health, The University of British Columbia, Vancouver, BC V6T 1Z4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaiwen","family":"Mu","sequence":"additional","affiliation":[{"name":"Food, Nutrition and Health, The University of British Columbia, Vancouver, BC V6T 1Z4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Guillaume","family":"Rheault","sequence":"additional","affiliation":[{"name":"Institut de biologie int\u00e9grative et des syst\u00e8mes (IBIS), Universit\u00e9 Laval, Quebec City, QC G1V 0A6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8315-5937","authenticated-orcid":false,"given":"Roger C.","family":"Levesque","sequence":"additional","affiliation":[{"name":"Institut de biologie int\u00e9grative et des syst\u00e8mes (IBIS), Universit\u00e9 Laval, Quebec City, QC G1V 0A6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David D.","family":"Kitts","sequence":"additional","affiliation":[{"name":"Food, Nutrition and Health, The University of British Columbia, Vancouver, BC V6T 1Z4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pascal","family":"Delaquis","sequence":"additional","affiliation":[{"name":"Agriculture and Agri-Food Canada, Summerland, BC V0H 1Z0, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lawrence","family":"Goodridge","sequence":"additional","affiliation":[{"name":"Food Science Department, University of Guelph, Guelph, ON N1G 2W1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2468-2483","authenticated-orcid":false,"given":"Siyun","family":"Wang","sequence":"additional","affiliation":[{"name":"Food, Nutrition and Health, The University of British Columbia, Vancouver, BC V6T 1Z4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1086\/650733","article-title":"International Collaboration on Enteric Disease \u2018Burden of Illness\u2019 Studies. The global burden of nontyphoidal Salmonella gastroenteritis","volume":"50","author":"Majowicz","year":"2010","journal-title":"Clin. Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"941","DOI":"10.3201\/eid2106.140999","article-title":"Global burden of invasive nontyphoidal Salmonella disease, 2010","volume":"21","author":"Ao","year":"2015","journal-title":"Emerg. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2015\/520179","article-title":"Salmonella enterica: Survival, colonization, and virulence differences among serovars","volume":"2015","author":"Andino","year":"2014","journal-title":"Sci. World J."},{"key":"ref_4","unstructured":"(2019, August 30). Reports of Selected Salmonella Outbreak Investigations, Available online: https:\/\/www.cdc.gov\/salmonella\/outbreaks.html."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2193","DOI":"10.3389\/fmicb.2017.02193","article-title":"Characterization of four novel bacteriophages isolated from British Columbia for control of non-typhoidal Salmonella in vitro and on sprouting alfalfa seeds","volume":"8","author":"Fong","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_6","unstructured":"(2019, September 02). Global Priority List of Antibiotic-Resistant Bacteria to Guide Research Discovery and Development of New Antibiotics. Available online: http:\/\/www.who.int\/entity\/medicines\/publications\/WHO-PPL-Short_Summary_25Feb-ET_NM_WHO.pdf? ua=1."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.3389\/fmicb.2015.01271","article-title":"On-demand isolation of bacteriophages against drug-resistant bacteria for personalized phage therapy","volume":"6","author":"Mattila","year":"2015","journal-title":"Front. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/ja.2010.62","article-title":"Antibiotic discovery in the twenty-first century: Current trends and future perspectives","volume":"63","author":"Donadio","year":"2010","journal-title":"J. Antibiot."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.bcp.2016.09.025","article-title":"Antibiotics in late clinical development","volume":"133","author":"Fernandes","year":"2017","journal-title":"Biochem. Pharmacol."},{"key":"ref_10","first-page":"1177","article-title":"Bacteriophage procurement for therapeutic purposes","volume":"7","author":"Zaczek","year":"2016","journal-title":"Front. Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1146\/annurev-food-030713-092415","article-title":"Phage therapy in the food industry","volume":"5","author":"Endersen","year":"2014","journal-title":"Ann. Rev. Food Sci. Technol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Filippov, A.A., Sergueev, K.V., He, Y., Huang, X.Z., Gnade, B.T., Mueller, A.J., and Nikolich, M.P. (2011). Bacteriophage-resistant mutants in Yersinia pestis: Identification of phage receptors and attenuation for mice. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0025486"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1111\/j.1472-765X.2007.02242.x","article-title":"Salmonella enterica phage-resistant mutant colonies display an unusual phenotype in the presence of phage Felix 01","volume":"45","author":"Coffey","year":"2007","journal-title":"Lett. Appl. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Seed, K.D. (2015). Battling phages: How bacteria defend against viral attack. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1004847"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1038\/nature10172","article-title":"Genomic island variability facilitates Prochlorococcus-virus coexistence","volume":"474","author":"Avrani","year":"2011","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"6599","DOI":"10.1128\/JB.187.18.6599-6600.2005","article-title":"Yersinia pestis is viable with endotoxin composed of only lipid A","volume":"187","author":"Tan","year":"2005","journal-title":"J. Bacteriol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"26717","DOI":"10.1038\/srep26717","article-title":"Phage selection restores antibiotic sensitivity in MDR Pseudomonas aeruginosa","volume":"6","author":"Chan","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.tim.2015.11.009","article-title":"Trade-off mechanisms shaping the diversity of bacteria","volume":"24","author":"Ferenci","year":"2016","journal-title":"Trends Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1128\/AEM.03494-13","article-title":"Core lipopolysaccharide-specific phage SSU5 as an auxiliary component of a phage cocktail for Salmonella biocontrol","volume":"80","author":"Kim","year":"2014","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_20","first-page":"1","article-title":"Screening of polyvalent phage- resistant Escherichia coli strains based on phage receptor analysis","volume":"10","author":"Li","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1128\/AEM.06231-11","article-title":"Characterization and comparative genomic analysis of a novel bacteriophage, SFP10, simultaneously inhibiting both Salmonella enterica and Escherichia coli O157: H7","volume":"78","author":"Park","year":"2012","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Shin, H., Lee, J.H., Kim, H., Choi, Y., Heu, S., and Ryu, S. (2012). Receptor diversity and host interaction of bacteriophages infecting Salmonella enterica serovar Typhimurium. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0043392"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1093\/nar\/gkm360","article-title":"CRISPRFinder: A web tool to identify clustered regularly interspaced short palindromic repeats","volume":"35","author":"Grissa","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_24","unstructured":"(2019, September 10). Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS). Available online: http:\/\/publications.gc.ca\/collections\/collection_2018\/aspc-phac\/HP2-4- 2016-eng.pdf."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e00068-19","DOI":"10.1128\/mSystems.00068-19","article-title":"Global transcriptomic analysis of the interactions between phage \u03c6abp1 and extensively drug-resistant Acinetobacter baumannii","volume":"4","author":"Yang","year":"2019","journal-title":"MSystems"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1128\/AAC.03876-14","article-title":"16S rRNA gene mutations associated with decreased susceptibility to tetracycline in Mycoplasma bovis","volume":"59","author":"Amram","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1098\/rspb.2015.1270","article-title":"Costs of CRISPR-Cas-mediated resistance in Streptococcus thermophilus","volume":"282","author":"Vale","year":"2015","journal-title":"Proc. R. Soc. B"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1128\/MMBR.00044-12","article-title":"Diverse functions of restriction-modification systems in addition to cellular defense","volume":"77","author":"Vasu","year":"2013","journal-title":"Microbiol. Mol. Rev."},{"key":"ref_29","first-page":"248849","article-title":"Comparative transcriptomics reveals a conserved bacterial adaptive phage response (BAPR) to viral predation","volume":"2018","author":"Blasdel","year":"2018","journal-title":"BioRxiv"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Sacher, J., Flint, A., Butcher, J., Blasdel, B., Reynolds, H., Lavigne, R., and Szymanski, C. (2018). Transcriptomic analysis of the Campylobacter jejuni response to T4-like phage NCTC 12673 infection. Viruses, 10.","DOI":"10.3390\/v10060332"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6894","DOI":"10.1128\/AEM.00928-06","article-title":"Inactivation of adhesion and invasion of food-borne Listeria monocytogenes by bacteriocin-producing Bifidobacterium strains of human origin","volume":"72","author":"Moroni","year":"2006","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40793-016-0218-y","article-title":"Complete genome sequence of the Salmonella enterica serovar Enteritidis bacteriophages fSE1C and fSE4C isolated from food matrices","volume":"12","author":"Santander","year":"2017","journal-title":"Stand. Genome Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2735","DOI":"10.1073\/pnas.041613098","article-title":"Programmed cell death mediated by ced-3 and ced-4 protects Caenorhabditis elegans from Salmonella Typhimurium-mediated killing","volume":"98","author":"Aballay","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1128\/IAI.74.3.1555-1564.2006","article-title":"The outer core lipopolysaccharide of Salmonella enterica serovar Typhi is required for bacterial entry into epithelial cells","volume":"74","author":"Hoare","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1128\/IAI.66.1.43-51.1998","article-title":"Role of flagella in pathogenesis of Pseudomonas aeruginosa pulmonary infection","volume":"66","author":"Feldman","year":"1998","journal-title":"Infect. Immun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1078\/1438-4221-00173","article-title":"The role of motility as a virulence factor in bacteria","volume":"291","author":"Josenhans","year":"2002","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Laanto, E., Bamford, J.K., Laakso, J., and Sundberg, L.R. (2012). Phage-driven loss of virulence in a fish pathogenic bacterium. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0053157"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1992","DOI":"10.1053\/gast.2002.37074","article-title":"Helicobacter pylori infection in mice: Role of outer membrane proteins in colonization and inflammation","volume":"123","author":"Yamaoka","year":"2002","journal-title":"Gastroenterology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1128\/IAI.01165-12","article-title":"The type VI secretion system encoded in Salmonella pathogenicity island 19 is required for Salmonella enterica serotype Gallinarum survival within infected macrophages","volume":"81","author":"Blondel","year":"2013","journal-title":"Infect. Immun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e5044","DOI":"10.1073\/pnas.1608858113","article-title":"Salmonella Typhimurium utilizes a T6SS-mediated antibacterial weapon to establish in the host gut","volume":"113","author":"Sana","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Wang, J., Zhou, Z., He, F., Ruan, Z., Jiang, Y., Hua, X., and Yu, Y. (2018). The role of the type VI secretion system vgrG gene in the virulence and antimicrobial resistance of Acinetobacter baumanii ATCC 19606. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0192288"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"20150021","DOI":"10.1098\/rstb.2015.0021","article-title":"Type VI secretion system: Secretion by a contractile nanomachine","volume":"370","author":"Basler","year":"2015","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1073\/pnas.0510322103","article-title":"Identification of a conserved bacterial protein secretion system in Vibrio cholera using the Dictyostelium host model system","volume":"103","author":"Pukatzki","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.vetmic.2019.01.006","article-title":"The SPI-19 encoded type-six secretion-systems (T6SS) of Salmonella enterica serovars Gallinarum and Dublin play different roles during infection","volume":"230","author":"Schroll","year":"2019","journal-title":"Vet. Microbiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.chom.2013.11.008","article-title":"A view to a kill: The bacterial type VI secretion system","volume":"15","author":"Ho","year":"2014","journal-title":"Cell Host Microbe"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1080\/21505594.2019.1573491","article-title":"Characterization of multiple type-VI secretion system (T6SS) VgrG proteins in the pathogenicity and antibacterial activity of porcine extra-intestinal pathogenic Escherichia Coli","volume":"10","author":"Zong","year":"2019","journal-title":"Virulence"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1098\/rstb.2011.0209","article-title":"Structural biology of type VI secretion systems","volume":"367","author":"Cascales","year":"2012","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.mib.2008.01.006","article-title":"Type VI secretion: A beginner\u2019s guide","volume":"11","author":"Bingle","year":"2008","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1093\/gbe\/evy140","article-title":"Patterns of nucleotide deletion and insertion inferred from bacterial pseudogenes","volume":"10","author":"Danneels","year":"2018","journal-title":"Genome Biol. Evol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1093\/gbe\/evt033","article-title":"Sequence context of indel mutations and their effect on protein evolution in a bacterial endosymbiont","volume":"5","author":"Williams","year":"2013","journal-title":"Genome Biol. Evol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"6110","DOI":"10.1128\/AEM.01421-13","article-title":"Evolution of Pseudomonas aeruginosa virulence as a result of phage predation","volume":"79","author":"Hosseinidoust","year":"2013","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Sistrom, M., Park, D., O\u2019Brien, H.E., Wang, Z., Guttman, D.S., Townsend, J.P., and Turner, P.E. (2015). Genomic and gene-expression comparisons among phage-resistant type-IV pilus mutants of Pseudomonas syringae pathovar phaseolicola. PLoS ONE, 10.","DOI":"10.1101\/025106"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.virusres.2016.04.020","article-title":"Bacteriophages with potential to inactivate Salmonella Typhimurium: Use of single phage suspensions and phage cocktails","volume":"220","author":"Pereira","year":"2016","journal-title":"Virus Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1038\/nprot.2007.521","article-title":"Agar and broth dilution methods to determine the minimal inhibitory concentration (MIC) of antimicrobial substances","volume":"3","author":"Wiegand","year":"2008","journal-title":"Nat. Prot."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1099\/0022-1317-49-6-503","article-title":"Comparative study of the invasiveness of Salmonella serotypes Typhimurium, Choleraesuis and Dublin for Caco-2 cells, HEp-2 cells and rabbit ileal epithelia","volume":"49","author":"Bolton","year":"2000","journal-title":"J. Med. Microbiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.mimet.2005.10.017","article-title":"Invasion assay of Listeria monocytogenes using Vero and Caco-2 cells","volume":"66","author":"Yamada","year":"2006","journal-title":"J. Microbiol. Methods"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Tritt, A., Eisen, J.A., Facciotti, M.T., and Darling, A.E. (2012). An integrated pipeline for de novo assembly of microbial genomes. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0042304"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1101\/gr.2289704","article-title":"Mauve: Multiple alignment of conserved genomic sequence with rearrangements","volume":"14","author":"Darling","year":"2004","journal-title":"Genome Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"W537","DOI":"10.1093\/nar\/gky379","article-title":"The Galaxy platform for accessible, reproducible and collaborative biomedical analyses: 2018 update","volume":"46","author":"Afgan","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: A flexible trimmer for Illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1093\/bioinformatics\/btu153","article-title":"Prokka: Rapid prokaryotic genome annotation","volume":"30","author":"Seemann","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.1923","article-title":"Fast gapped-read alignment with Bowtie 2","volume":"9","author":"Langmead","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1101\/gr.107524.110","article-title":"The genome analysis toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data","volume":"20","author":"McKenna","year":"2010","journal-title":"Genome Res."},{"key":"ref_64","unstructured":"Garrison, E., and Marth, G. (2020, February 12). Haplotype-Based Variant Detection from Short-Read Sequencing. Available online: https:\/\/arxiv.org\/abs\/1207.3907."},{"key":"ref_65","first-page":"1307","article-title":"Rapid whole-genome sequencing for surveillance of Salmonella enterica serovar Enteritidis","volume":"20","author":"Allard","year":"2014","journal-title":"Emerg. Infect. Dis."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/5\/1883\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:05:42Z","timestamp":1760173542000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/5\/1883"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,10]]},"references-count":65,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2020,3]]}},"alternative-id":["ijms21051883"],"URL":"https:\/\/doi.org\/10.3390\/ijms21051883","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,10]]}}}