Differences between the global transcriptomes of Salmonella enterica serovars Dublin and Cerro during infection of bovine epithelial cells

Authors: Salaheen, Serajus; Kim, Seonwoo; Van Kessel, Jo Ann; Haley, Bradd

Submitted to: BMC Genomics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/22/2022
Publication Date: 7/8/2022
Citation: Salaheen, S., Kim, S., Van Kessel, J.S., Haley, B.J. 2022. Differences between the global transcriptomes of Salmonella enterica serovars Dublin and Cerro during infection of bovine epithelial cells. BMC Genomics. https://doi.org/10.1186/s12864-022-08725-z.
DOI: https://doi.org/10.1186/s12864-022-08725-z

Interpretive Summary: Salmonella enterica (S. enterica) is a major cause of infection-related morbidity among humans and domesticated animals worldwide. A small percentage of the approximately 2500 known serovars of S. enterica account for most human infections, but all S. enterica serovars are considered potential human pathogens. Many serovars can asymptomatically infect food-producing animals and these animals can shed the bacteria in their feces, thereby potentially contaminating foods, other animals, humans, and the environment causing an under-appreciated public health concern. Dairy cows are known reservoirs of S. enterica and the impact and/or severity of infection in cattle is highly variable and often serovar-dependent. There are significant knowledge gaps in our understanding of genomic and transcriptomic features that are responsible for the differential interactions between S. enterica serovars with bovine host cells. This study compared the global transcriptomes of the highly pathogenic, bovine-adapted S. Dublin and the less pathogenic, bovine-adapted S. Cerro during interactions with bovine epithelial cells to identify genes that impact serovar-related outcomes of S. enterica infections in cattle. Results indicated that the higher levels of invasiveness of the S. Dublin strains to bovine epithelial cells compared with the S. Cerro strains appeared to be a result of a complex set of differentially expressed genes – some genes were upregulated in S. Dublin strains and others were upregulated in S. Cerro strains. This study furthered our understanding of the potential S. enterica genes that may be responsible for symptomatic or asymptomatic infection/colonization of two bovine-adapted S. enterica serovars in cattle. Results from this study may be used to identify specific drug targets/management strategies that can be leveraged to reduce occurrences of S. enterica serovars in dairy animals.

Technical Abstract: The impact of S. enterica colonization in cattle is highly variable and often serovar-dependent. The aim of this study was to compare the global transcriptomes of highly pathogenic bovine-adapted S. enterica serovar Dublin and the less pathogenic bovine-adapted serovar Cerro during interactions with bovine epithelial cells, to identify genes that impact serovar-related outcomes of S. enterica infections in dairy animals. Bovine epithelial cells were infected with S. enterica strains from serovars Dublin and Cerro and bacterial RNA sequencing was conducted. The total number of paired-end reads uniquely mapped to non-rRNA and non-tRNA genes in the reference genomes ranged between 12.1 M and 23.4 M (median: 15.7 M). In total, 360 differentially expressed genes (DEGs) were identified with at least 2-fold differences in the transcript abundances between S. Dublin and S. Cerro (false discovery rate = 5%). Most DEGs (17.5%, 63 of 360 genes) between the two serovars were located on the genomic regions potentially associated with Salmonella Pathogenicity Islands (SPIs). DEGs potentially located in the SPI-regions that were upregulated (by =2-fold) in the S. Dublin compared with S. Cerro included: 37 (of 44) SPI-1 genes encoding mostly Type 3 Secretion System (T3SS) apparatus and effectors; all of the 6 SPI-4 genes encoding type I secretion apparatus (siiABCDEF); T3SS effectors and chaperone (sopB, pipB, and sigE) located in SPI-5; type VI secretion system associated protein coding genes (sciJKNOR) located in SPI-6; and T3SS effector sopF in SPI-11. Additional major functional categories of DEGs included transcription regulators (n = 25), amino acid transport and metabolism (n = 20), carbohydrate transport and metabolism (n = 20), energy production and metabolism (n = 19), cell membrane biogenesis (n = 18), and coenzyme transport and metabolism (n = 15). DEGs were further mapped to the metabolic pathways listed in the KEGG database; most genes of the fatty acid ß-oxidation pathway were upregulated/uniquely present in the S. Dublin strains compared with the S. Cerro strains. This study identifies potential genes of S. enterica that may be responsible for symptomatic or asymptomatic infection/colonization of two bovine-adapted serovars in cattle.