Genomic adaptation of Salmonella to antimicrobials and the human host

Salmonella is a well-known pathogen causing gastroenteritis in humans, with some types leading to lethal bloodstream infections. The rise of antimicrobial resistance (AMR) in Salmonella is a significant concern, exacerbated by indications that certain strains are becoming more adapted to humans, potentially facilitating AMR spread. This PhD study aims to investigate genomic adaptations linked to AMR and explore transcriptomic changes associated with host adaptation. First, fluoroquinolone resistance (FQR) in Salmonella was examined by reviewing studies that employed whole genome sequencing (WGS). We found that the dominant presence of the S. Typhi H58 clade was associated with hindering typhoid fever treatment in Asia. Limited data exists on fluoroquinolone-resistant invasive non-typhoidal Salmonella (iNTS) in Africa, despite its high prevalence. Non-typhoidal Salmonella, infecting both animals and humans, displays greater diversity in plasmid-mediated quinolone resistance mechanisms compared to typhoidal Salmonella, highlighting the importance of a One Health approach to effectively monitor FQR spread and its source. Next, Salmonella Concord was studied, which is associated with severe gastrointestinal and bloodstream infections primarily in patients from Ethiopia and Ethiopian adoptees. This pathogen is noteworthy for frequently exhibiting co-resistance to multiple antimicrobials. The evolutionary history and geographic distribution of S. Concord have been unclear. Genomic analysis of 284 S. Concord isolates collected between 1944 and 2022 reveals that S. Concord is a polyphyletic serovar, falling into three Salmonella super-lineages. The majority of S. Concord isolates group within super-lineage A, consisting of eight lineages. Four lineages are found in multiple countries with low AMR levels, while the others are linked to Ethiopia, displaying high AMR to antimicrobials used for invasive Salmonella treatment in low- and middle-income countries. Horizontal gene transfer events involving diverse plasmids and chromosomal islands contribute to the spread of AMR genes. Last, the process of Salmonella adaptation to the human host was studied, focusing on transcriptional rewiring. Rather than investigating the coding genome, a distinctive approach of analysing gene co-expression patterns was used and first implemented in the R programming language. The comparison of gene co-expression conservation between two S. Typhimurium strains reveals little divergence, potentially due to a recent evolutionary split. Transcriptional rewiring was observed in the Type Three Secretion System 1 (T3SS-1), possibly resulting from genomic differences. However, more expression data is needed to confirm this hypothesis. Understanding the aspects addressed in this thesis is crucial for combating AMR and improving our knowledge of Salmonella infections in humans.