Details

Autor(en) / Beteiligte

• Zhu, Xiaojun

Titel

Impact of the Accessory Genome upon the Biology of African Salmonella Enterica Serovar Typhimurium ST313

Ort / Verlag

ProQuest Dissertations Publishing

Erscheinungsjahr

2022

Link zum Volltext

Quelle

Sociological Abstracts

Beschreibungen/Notizen

• Invasive non-typhoidal Salmonella disease (iNTS) is caused by certain variants of Salmonella enterica serovar Typhimurium, and is a particular clinical problem in sub-Saharan Africa. A novel sequence type of S. Typhimurium, ST313, is responsible for about two thirds of human bloodstream infections. Previously, RNA-seq based comparative transcriptomic analysis of ST313 and the well-studied ST19 sequence type identified genes and sRNAs that were differentially expressed in 16 infection-relevant growth conditions, but many of these genes remain to be studied at a functional level. This thesis is focused on the investigation of the links between the accessory genome and differentially-expressed genes of S. Typhimurium ST313 and ST19.Several ST313 isolates from the UK were recently discovered that are closely related to ST313 lineages from Africa, and cause gastroenteritis but not bloodstream infection. The genome-based analysis of the UK ST313 isolates revealed several homologs of novel prophages BTP1 and BTP5 in African ST313. An experimental approach showed that these homologs of BTP1 have a similar host range to the African ST313-derived BTP1 phage, and a range of different levels of spontaneous induction.Recent phylogenetic analysis of African ST313 identified a novel sub-lineage, L2.2 represented by strain D37712. RNA-seq based transcriptomic analysis showed high expression of SPI2 genes by L2.2 in a non-inducing (NonSPI2) growth condition compared with ST313 lineage L2. This finding was confirmed by a GFP transcriptional fusion-based strategy and flow cytometry. A series of competition experiments revealed that the novel ST313 sub-lineage L2.2 has greater fitness than ST313 L2 in the NonSPI2 growth condition.The comparative transcriptomic data of ST313 identified repression of the essential chromosomal gene cysS, coupled with high level of expression of a paralog of cysS gene carried by the novel plasmid pBT1. The expression of the chromosomal cysS promoter was found to be repressed by pBT1, and modulated by a novel pBT1-encoded genetic region between pBT1-0051 and traL.By providing new information about the accessory genome of Salmonella ST313, as well as the relative fitness of Lineage 2/Lineage 2.2, this thesis contributes to a better understanding of the evolution and success of Salmonella ST313 in Africa.