Abstract: Objective: The purpose of this research was to explore the global transcriptome response of Salmonella typhimurium under acid stress and non-acid stress conditions, analyze the expression levels of differentially expressed genes (DEGs), and elucidate the metabolic pathways related to the acid tolerance response (ATR) of S. typhimurium. Methods: Transcriptome sequencing and bioinformatics were used to select the ATR-related DEGs, whcih were then verified by real-time polymerase chain reaction (real-time PCR). Results: In response to acid stress, a total of 683 DEGs were identified in S. typhimurium, including 343 up-regulated and 340 down-regulated ones. The DEGs involved in cell movements, amino acid metabolism, and cell membrane composition were up-regulated, thus making S. typhimurium adapt to the acidic environment quickly. The up-regulation of the genes associated with carbohydrate metabolism could provide more energy for S. typhimurium to adapt to the acidic environment rapidly. Meanwhile, the down-regulation of the genes involved in energy metabolism pathways such as pyrimidine metabolism could reduce the energy consumption of S. typhimurium to maintain these essential metabolic processes. The up-regulation of the genes related to stress reponse response could enhance the cross-protective resistance of S. typhimurium, and the up-regulation of the virulence-related genes such as flagella, outer membrane protein, and lipopolysaccharide could strengthen the virulence of acid-adpted S. typhimurium. Additionally, the results of real-time PCR were consistent with these transcriptomic data. Conclusion: Acid stress can significantly enhance the acid tolerance of S. typhimurium, and the signaling pathways related to metabolism and cellular processes may play major roles in this effect. This study provides a theoretical basis for further understanding the ATR of S. typhimurium and better controlling its contamination in foods.

Key words: Salmonella typhimurium; acid adaptation; acid tolerance response; RNA sequencing; real-time polymerase chain reaction