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Salmonella enterica serovar Typhimurium ST313 causes the majority of iNTS in Malawi. We performed an intensive comparative genomic analysis of 608 S. Typhimurium ST313 isolates dating between 1996 and 2018 from Blantyre, Malawi. We discovered that following the arrival of the well-characterized S. Typhimurium ST313 lineage 2 in 1999, two multidrug-resistant variants emerged in Malawi in 2006 and 2008, designated sublineages 2.2 and 2.3, respectively. The majority of S. Typhimurium isolates from human bloodstream infections in Malawi now belong to sublineages 2.2 or 2.3. To understand the emergence of the prevalent ST313 sublineage 2.2, we studied two representative strains, D23580 (lineage 2) and D37712 (sublineage 2.2). The chromosome of ST313 lineage 2 and sublineage 2.2 only differed by 29 SNPs\/small indels and a 3\u00a0kb deletion of a Gifsy-2 prophage region including the sseI pseudogene. Lineage 2 and sublineage 2.2 had distinctive plasmid profiles. The transcriptome was investigated in 15 infection-relevant in vitro conditions and within macrophages. During growth in physiological conditions that do not usually trigger S. Typhimurium SPI2 gene expression, the SPI2 genes of D37712 were transcriptionally active. We identified down-regulation of flagellar genes in D37712 compared with D23580. Following phenotypic confirmation of transcriptomic differences, we discovered that sublineage 2.2 had increased fitness compared with lineage 2 during mixed growth in minimal media. We speculate that this competitive advantage is contributing to the emergence of sublineage 2.2 in Malawi.<\/jats:p>","DOI":"10.1093\/femsml\/uqae005","type":"journal-article","created":{"date-parts":[[2024,3,27]],"date-time":"2024-03-27T18:34:17Z","timestamp":1711564457000},"source":"Crossref","is-referenced-by-count":10,"title":["<i>Salmonella enterica<\/i> serovar Typhimurium ST313 sublineage 2.2 has emerged in Malawi with a characteristic gene expression signature and a fitness advantage"],"prefix":"10.1093","volume":"5","author":[{"given":"Benjamin","family":"Kumwenda","sequence":"first","affiliation":[{"name":"School of Life Sciences and Allied Health Professions, Kamuzu University of Health Sciences Blantyre , Blantyre, 265 ,","place":["Malawi"]},{"name":"Institute of Infection, Veterinary & Ecological Sciences, University of Liverpool , Liverpool, L69 7ZB ,","place":["United Kingdom"]},{"name":"Malawi\u2013Liverpool\u2013Wellcome Programme , Blantyre, 3 ,","place":["Malawi"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roc\u00edo","family":"Canals","sequence":"additional","affiliation":[{"name":"Institute of Infection, Veterinary & Ecological Sciences, University of Liverpool , Liverpool, L69 7ZB ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2750-1599","authenticated-orcid":false,"given":"Alexander V","family":"Predeus","sequence":"additional","affiliation":[{"name":"Institute of Infection, Veterinary & Ecological Sciences, University of Liverpool , Liverpool, L69 7ZB ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojun","family":"Zhu","sequence":"additional","affiliation":[{"name":"Institute of Infection, Veterinary & Ecological Sciences, University of Liverpool , Liverpool, L69 7ZB ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0461-1530","authenticated-orcid":false,"given":"Carsten","family":"Kr\u00f6ger","sequence":"additional","affiliation":[{"name":"Institute of Infection, Veterinary & Ecological Sciences, University of Liverpool , Liverpool, L69 7ZB ,","place":["United Kingdom"]},{"name":"Department of Microbiology, Moyne Institute of Preventive Medicine, School of Genetics and Microbiology, Trinity College Dublin , Dublin, D02 PN40 ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caisey","family":"Pulford","sequence":"additional","affiliation":[{"name":"Institute of Infection, Veterinary & Ecological Sciences, University of Liverpool , Liverpool, L69 7ZB ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Wenner","sequence":"additional","affiliation":[{"name":"Institute of Infection, Veterinary & Ecological Sciences, University of Liverpool , Liverpool, L69 7ZB ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lizeth Lacharme","family":"Lora","sequence":"additional","affiliation":[{"name":"Institute of Infection, Veterinary & Ecological Sciences, University of Liverpool , Liverpool, L69 7ZB ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7480-9545","authenticated-orcid":false,"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Infection, Veterinary & Ecological Sciences, University of Liverpool , Liverpool, L69 7ZB ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si\u00e2n V","family":"Owen","sequence":"additional","affiliation":[{"name":"Institute of Infection, Veterinary & Ecological Sciences, University of Liverpool , Liverpool, L69 7ZB ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2253-6036","authenticated-orcid":false,"given":"Dean","family":"Everett","sequence":"additional","affiliation":[{"name":"Department of Public Health and Epidemiology, College of Medicine and Health Sciences, Khalifa University , Abu Dhabi, P.O. 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