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Unfortunately, the mechanisms that drive the evolution of such continuously adapting pathogens remain poorly understood. Here, we combine molecular genotyping with network science and Bayesian inference to infer directed genotype networks\u2014and trace the emergence and evolutionary paths\u2014of<jats:italic>Salmonella<\/jats:italic>Typhimurium (STM) from nine years of Australian disease surveillance data. We construct networks where nodes represent STM strains and directed edges represent evolutionary steps, presenting evidence that the structural (i.e., network-based) features are relevant to understanding the functional (i.e., fitness-based) progression of co-evolving STM strains. This is argued by showing that outbreak severity, i.e., prevalence, correlates to: (i) the network path length to the most prevalent node (<jats:italic>r<\/jats:italic>= \u22120.613,<jats:italic>N<\/jats:italic>= 690); and (ii) the network connected-component size (<jats:italic>r<\/jats:italic>= 0.739). Moreover, we uncover distinct exploration-exploitation pathways in the genetic space of STM, including a strong evolutionary drive through a transition region. This is examined via the 6,897 distinct evolutionary paths in the directed network, where we observe a dominant 66% of these paths decrease in network centrality, whilst increasing in prevalence. Furthermore, 72.4% of all paths originate in the transition region, with 64% of those following the dominant direction. Further, we find that the length of an evolutionary path strongly correlates to its increase in prevalence (<jats:italic>r<\/jats:italic>= 0.497). Combined, these findings indicate that longer evolutionary paths result in genetically rare and virulent strains, which mostly evolve from a single transition point. Our results not only validate our widely-applicable approach for inferring directed genotype networks from data, but also provide a unique insight into the elusive functional and structural drivers of STM bacteria.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1008401","type":"journal-article","created":{"date-parts":[[2020,10,30]],"date-time":"2020-10-30T17:54:17Z","timestamp":1604080457000},"page":"e1008401","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Inferring evolutionary pathways and directed genotype networks of foodborne pathogens"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5041-4090","authenticated-orcid":true,"given":"Oliver 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Newman","year":"2003","journal-title":"SIAM review"},{"key":"pcbi.1008401.ref029","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1140\/epjb\/e2008-00473-5","article-title":"Assortativeness and information in scale-free networks","volume":"67","author":"M Piraveenan","year":"2009","journal-title":"The European Physical Journal B"},{"key":"pcbi.1008401.ref030","doi-asserted-by":"crossref","first-page":"e1006554","DOI":"10.1371\/journal.pcbi.1006554","article-title":"A graph-based evidence synthesis approach to detecting outbreak clusters: An application to dog rabies","volume":"14","author":"A Cori","year":"2018","journal-title":"PLOS Computational Biology"},{"issue":"2","key":"pcbi.1008401.ref031","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.mimet.2004.06.014","article-title":"Multiple-locus variable-number tandem-repeats analysis of Salmonella enterica subsp. enterica serovar Typhimurium using PCR multiplexing and multicolor capillary electrophoresis","volume":"59","author":"BA Lindstedt","year":"2004","journal-title":"Journal of Microbiological Methods"},{"key":"pcbi.1008401.ref032","doi-asserted-by":"crossref","first-page":"388","DOI":"10.3201\/eid1303.060460","article-title":"Tandem repeat analysis for surveillance of human Salmonella Typhimurium infections","volume":"13","author":"M Torpdahl","year":"2007","journal-title":"Emerging infectious diseases"},{"issue":"18","key":"pcbi.1008401.ref033","doi-asserted-by":"crossref","first-page":"7711","DOI":"10.1073\/pnas.0702154104","article-title":"The generation of influenza outbreaks by a network of host immune responses against a limited set of antigenic types","volume":"104","author":"M Recker","year":"2007","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"9","key":"pcbi.1008401.ref034","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.3390\/v4091438","article-title":"Evasion of influenza A viruses from innate and adaptive immune responses","volume":"4","author":"CE Van de Sandt","year":"2012","journal-title":"Viruses"},{"issue":"3","key":"pcbi.1008401.ref035","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1073\/pnas.0409065102","article-title":"Evasion of antibody neutralization in emerging severe acute respiratory syndrome coronaviruses","volume":"102","author":"Zy Yang","year":"2005","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"21","key":"pcbi.1008401.ref036","doi-asserted-by":"crossref","first-page":"E4251","DOI":"10.1073\/pnas.1618310114","article-title":"Coronavirus nonstructural protein 15 mediates evasion of dsRNA sensors and limits apoptosis in macrophages","volume":"114","author":"X Deng","year":"2017","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"3","key":"pcbi.1008401.ref037","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1086\/589861","article-title":"Foodborne disease in Australia: the OzFoodNet 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Salmonella: what is it, and how can you protect against it? (CSIRO Scope, 17 February 2016); 2016. https:\/\/blog.csiro.au\/what-is-salmonella."},{"issue":"15","key":"pcbi.1008401.ref041","doi-asserted-by":"crossref","DOI":"10.2807\/ese.14.15.19174-en","article-title":"Development of a new nomenclature for Salmonella Typhimurium multilocus variable number of tandem repeats analysis (MLVA)","volume":"14","author":"JT Larsson","year":"2009","journal-title":"Eurosurveillance"},{"key":"pcbi.1008401.ref042","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-4899-3324-9","volume-title":"Density estimation for statistics and data analysis","author":"BW Silverman","year":"1986"},{"issue":"4","key":"pcbi.1008401.ref043","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1128\/CMR.00056-16","article-title":"Navigating microbiological food safety in the era of whole-genome sequencing","volume":"29","author":"J Ronholm","year":"2016","journal-title":"Clinical microbiology reviews"},{"key":"pcbi.1008401.ref044","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1093\/gbe\/evq077","article-title":"A survey of combinatorial methods for phylogenetic networks","volume":"3","author":"DH Huson","year":"2011","journal-title":"Genome biology and evolution"},{"key":"pcbi.1008401.ref045","article-title":"Phylogenetic network analysis of SARS-CoV-2 genomes","author":"P Forster","year":"2020","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"6","key":"pcbi.1008401.ref046","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.1073\/pnas.0705414105","article-title":"Tipping elements in the Earth\u2019s climate system","volume":"105","author":"TM Lenton","year":"2008","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"7260","key":"pcbi.1008401.ref047","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/nature08227","article-title":"Early-warning signals for critical transitions","volume":"461","author":"M Scheffer","year":"2009","journal-title":"Nature"},{"key":"pcbi.1008401.ref048","unstructured":"Ward K, Franklin N, Furlong C, Polkinghorne B, Flint J. OzFoodNet\u2014Enhancing Foodborne Disease Surveillance across Australia. NSW 2013 OzFoodNet Annual Report; 2013. https:\/\/www.health.nsw.gov.au\/Infectious\/foodborne\/Publications\/NSW-ofn-annual-report-2013.pdf."},{"key":"pcbi.1008401.ref049","unstructured":"Communicable Diseases Branch, NSW Department of Health. OzFoodNet\u2014Enhancing Foodborne Disease Surveillance Across Australia. First Quarter Summary, 2011 NSW\/Hunter New England OFN sites combined; 2011. https:\/\/www.health.nsw.gov.au\/Infectious\/diseases\/Documents\/NSW-1st-quarterly-ofn-report-2011.pdf."},{"key":"pcbi.1008401.ref050","unstructured":"Franklin N, Furlong C, Ward K, Flint J. OzFoodNet\u2014Enhancing Foodborne Disease Surveillance Across Australia. 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