<i>Salmonella enterica</i> serovar Typhimurium ST313 sublineage 2.2 has emerged in Malawi with a characteristic gene expression signature and a fitness advantage.


Kumwenda, Benjamin, Canals, Rocío, Predeus, Alexander V ORCID: 0000-0002-2750-1599, Zhu, Xiaojun, Kröger, Carsten ORCID: 0000-0003-0461-1530, Pulford, Caisey, Wenner, Nicolas, Lora, Lizeth Lacharme, Li, Yan ORCID: 0000-0002-7480-9545, Owen, Siân V et al (show 7 more authors) (2024) <i>Salmonella enterica</i> serovar Typhimurium ST313 sublineage 2.2 has emerged in Malawi with a characteristic gene expression signature and a fitness advantage. microLife, 5. uqae005-.

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Abstract

Invasive non-typhoidal <i>Salmonella</i> (iNTS) disease is a serious bloodstream infection that targets immune-compromised individuals, and causes significant mortality in sub-Saharan Africa. <i>Salmonella enterica</i> serovar Typhimurium ST313 causes the majority of iNTS in Malawi. We performed an intensive comparative genomic analysis of 608 <i>S</i>. Typhimurium ST313 isolates dating between 1996 and 2018 from Blantyre, Malawi. We discovered that following the arrival of the well-characterized <i>S</i>. 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 <i>S</i>. 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 kb deletion of a Gifsy-2 prophage region including the <i>sseI</i> pseudogene. Lineage 2 and sublineage 2.2 had distinctive plasmid profiles. The transcriptome was investigated in 15 infection-relevant <i>in vitro</i> conditions and within macrophages. During growth in physiological conditions that do not usually trigger <i>S</i>. 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.

Item Type: Article
Uncontrolled Keywords: antibiotic resistance, comparative genomics, gene expression, lineage evolution, transcriptomics
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User: Symplectic Admin
Date Deposited: 19 Mar 2024 10:43
Last Modified: 02 May 2024 09:35
DOI: 10.1093/femsml/uqae005
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3179571
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