Unraveling the Impact of Short-Chain Fatty Acids on Virulence Genes in Salmonella Typhi: A Gene Expression Profiling Study under SCF-Induced Stress
DOI:
https://doi.org/10.36320/ajb/v15.i3.13000Keywords:
Salmonella Typhi, SCFs, T3SS-1, hilC, hilD, sipC, Salmonella TyphiAbstract
Abstract: Salmonella Typhi is a highly pathogenic bacterium that causes typhoid fever, a serious systematic infectious disease with significant global health implications. Short-chain fatty acids (SCFAs) influence gene expression in other Salmonella strains but their impact on Salmonella Typhi is unclear. This study investigates the impact of specific SCFAs (Sodium Butyrate and Sodium Propionate) on the expression of T3SS-1 virulence-associated genes (hilC, hilD, sipC) and a regulatory gene (ropE) in Salmonella Typhi. Sub-inhibitory concentrations of SCFAs were determined (50mg/ml), allowing analysis of their effects on bacterial behavior without inhibiting growth. Gene expression analysis using RT-qPCR revealed that both Sodium Butyrate and Sodium Propionate significantly downregulated hilC, hilD, and sipC genes, essential for activating virulence factors. However, the ropE gene remained unaffected. These findings suggest that SCFAs play a role in regulating virulence in Salmonella Typhi, consistent with previous research on other Salmonella strains. Understanding SCFAs' influence on Salmonella Typhi virulence could lead to targeted interventions for combatting Salmonella infections and improving public health.
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Tsolis RM, Kingsley RA, Townsend SM, Ficht TA, Adams LG, Bäumler AJ.(1999) Of mice, calves, and men. Comparison of the mouse typhoid model with other Salmonella infections. Adv Exp Med Biol. 1999;473:261-74. PMID: 10659367. DOI: https://doi.org/10.1007/978-1-4615-4143-1_28
Garner, C. D., Antonopoulos, D. A., Wagner, B., Duhamel, G. E., Keresztes, I., Ross, D. A, Young, V. B. and Altier, C. (2009). Perturbation of the small intestine microbial ecology by streptomycin alters pathology in a Salmonella enterica serovar Typhimurium murine model of infection. Infect. Immunity. 77:2691–2702. DOI: https://doi.org/10.1128/IAI.01570-08
Lawhon, S. D., Maurer, R., Suyemoto, M., & Altier, C. (2002). Intestinal short-chain fatty acids alter Salmonella typhimurium invasion gene expression and virulence through BarA/SirA. Molecular microbiology, 46(5), 1451–1464. https://doi.org/10.1046/j.1365-2958.2002.03268.x. DOI: https://doi.org/10.1046/j.1365-2958.2002.03268.x
Altier, C. (2005). Genetic and environmental control of Salmonella invasion. J. Microbiol. 43, 85–92.
Gantois, I., Ducatelle, R., Pasmans, F., Haesebrouck, F., Hautefort, I., Thompson, A., Hinton, J. C., & Van Immerseel, F. (2006). Butyrate specifically down-regulates salmonella pathogenicity island 1 gene expression. Applied and environmental microbiology, 72(1), 946–949. https://doi.org/10.1128/AEM.72.1.946-949.2006. DOI: https://doi.org/10.1128/AEM.72.1.946-949.2006
Parkhill, J., Dougan, G., James, K. D., Thomson, N. R., Pickard, D., Wain, J.,… Barrell, B. G. (2001). Complete genome sequence of a multiple drug resistant Salmonella enterica serovar Typhi CT18. Nature, 413(6858),848–852. https://doi.org/10.1038/35101607. DOI: https://doi.org/10.1038/35101607
McClelland, M., Sanderson, K. E., Clifton, S. W., Latreille, P., Porwollik, S., Sabo, A., …Wilson, R. K. (2004). Comparison of genome degradation in Paratyphi A and Typhi, human‐restricted serovars of Salmonella enterica that cause typhoid. Nature Genetics, 36(12), 1268–1274.https://doi.org/10.1038/ng1470. DOI: https://doi.org/10.1038/ng1470
Nuccio, S. & Baumler, A. (2014). Comparative Analysis of Salmonella Genomes Identifies a Metabolic Network for Escalating Growth in the Inflamed Gut. mBio. 5. 10.1128/mBio.00929-14. DOI: https://doi.org/10.1128/mBio.00929-14
Campbell, J.W., Morgan-Kiss, R.M., and Cronan, J.E., Jr. (2003). A new Escherichia coli metabolic competency: growth on fatty acids by a novel anaerobic beta-oxidation pathway. Mol. Microbiol. 47, 793–805. DOI: https://doi.org/10.1046/j.1365-2958.2003.03341.x
Lopez, C.A., Winter, S.E., Rivera-Chavez, F., Xavier, M.N., Poon, V., Nuccio, S.P., Tsolis, R.M., and Baumler, A.J. (2012). Phage-mediated acquisition of a type III secreted effector protein boosts growth of Salmonella by nitrate respiration. mBio 3, https://doi.org/10.1128/mBio.00143-12. DOI: https://doi.org/10.1128/mBio.00143-12
Lopez, C.A., Rivera-Chavez, F., Byndloss, M.X., and Baumler, A.J. (2015). The periplasmic nitrate reductase NapABC supports luminal growth of Salmonella enterica serovar typhimurium during colitis. Infect. Immun. 83, 3470–3478. DOI: https://doi.org/10.1128/IAI.00351-15
Abdulridha, F. M., & Kudhair, B. K. (2023). Evaluation of a rapid and reliable multiplex PCR assay for the detection of Salmonella Typhi in stool samples. Gene Reports, 33, 101812. https://doi.org/10.1016/j.genrep.2023.101812. DOI: https://doi.org/10.1016/j.genrep.2023.101812
Kim, J., 2011. CWZ Mini Boiling RNA Preparation. Smith College. URL https://www.science.smith.edu/cmbs/next-gen-sequencing/ (accessed 7.8.23).
Hung, C. C., Garner, C. D., Slauch, J. M., Dwyer, Z. W., Lawhon, S. D., Frye, J. G., McClelland, M., Ahmer, B. M., & Altier, C. (2013). The intestinal fatty acid propionate inhibits Salmonella invasion through the post-translational control of HilD. Molecular microbiology, 87(5), 1045–1060. https://doi.org/10.1111/mmi.12149. DOI: https://doi.org/10.1111/mmi.12149
Bronner, D. N., Faber, F., Olsan, E. E., Byndloss, M. X., Sayed, N. A., Xu, G., Yoo, W., Kim, D., Ryu, S., Lebrilla, C. B., & Bäumler, A. J. (2018). Genetic Ablation of Butyrate Utilization Attenuates Gastrointestinal Salmonella Disease. Cell host & microbe, 23(2), 266–273.e4. https://doi.org/10.1016/j.chom.2018.01.004 DOI: https://doi.org/10.1016/j.chom.2018.01.004
Lamas, A., Regal, P., Vázquez, B., Cepeda, A., & Franco, C. M. (2019). Short Chain Fatty Acids Commonly Produced by Gut Microbiota Influence Salmonellaenterica Motility, Biofilm Formation, and Gene Expression. Antibiotics (Basel, Switzerland), 8(4), 265. https://doi.org/10.3390/antibiotics8040265. DOI: https://doi.org/10.3390/antibiotics8040265
Gupta A, Bansal M, Wagle B, Sun X, Rath N, Donoghue A and Upadhyay A (2020) Sodium Butyrate Reduces Salmonella Enteritidis Infection of Chicken Enterocytes and Expression of Inflammatory Host Genes in vitro. Front. Microbiol. 11:553670. doi: 10.3389/fmicb.2020.553670. DOI: https://doi.org/10.3389/fmicb.2020.553670
Liu, J., Zhu, W., Qin, N., Ren, X., & Xia, X. (2022). Propionate and Butyrate Inhibit Biofilm Formation of Salmonella Typhimurium Grown in Laboratory Media and Food Models. Foods, 11(21), 3493. https://doi.org/10.3390/foods11213493. DOI: https://doi.org/10.3390/foods11213493
Schechter, L. M., S. M. Scott, and C. A. Lee. (1999). Two AraC/XylS family members can independently counteract the effect of repressing sequences upstream of the hilA promoter. Mol. Microbiol. 32:629. DOI: https://doi.org/10.1046/j.1365-2958.1999.01381.x
Schechter, L. M., & Lee, C. A. (2001). AraC/XylS family members, HilC and HilD, directly bind and derepress the Salmonella typhimurium hilA promoter. Molecular microbiology, 40(6), 1289–1299. https://doi.org/10.1046/j.1365-2958.2001.02462.x DOI: https://doi.org/10.1046/j.1365-2958.2001.02462.x
Lostroh, C. P., & Lee, C. A. (2001). The HilA box and sequences outside it determine the magnitude of HilA-dependent activation of P(prgH) from Salmonella pathogenicity island 1. Journal of bacteriology, 183(16), 4876–4885. https://doi.org/10.1128/JB.183.16.4876-4885.2001. DOI: https://doi.org/10.1128/JB.183.16.4876-4885.2001
Kaniga, K., Bossio, J. C., & Galán, J. E. (1994). The Salmonella typhimurium invasion genes invF and invG encode homologues of the AraC and PulD family of proteins. Molecular microbiology, 13(4), 555–568. https://doi.org/10.1111/j.1365-2958.1994.tb00450.x. DOI: https://doi.org/10.1111/j.1365-2958.1994.tb00450.x
Darwin, K. H., & Miller, V. L. (1999). InvF is required for expression of genes encoding proteins secreted by the SPI1 type III secretion apparatus in Salmonella typhimurium. Journal of bacteriology, 181(16), 4949–4954. https://doi.org/10.1128/JB.181.16.4949-4954.1999. DOI: https://doi.org/10.1128/JB.181.16.4949-4954.1999
Eichelberg, K., & Galán, J. E. (1999). Differential Regulation of Salmonella typhimurium Type III Secreted Proteins by Pathogenicity Island 1 (SPI-1)-Encoded Transcriptional Activators InvF and HilA. Infection and Immunity, 67(8), 4099-4105. https://doi.org/10.1128/iai.67.8.4099-4105.1999. DOI: https://doi.org/10.1128/IAI.67.8.4099-4105.1999
Darwin, K. H., & Miller, V. L. (2000). The putative invasion protein chaperone SicA acts together with InvF to activate the expression of Salmonella typhimurium virulence genes. Molecular microbiology, 35(4), 949–960. https://doi.org/10.1046/j.1365-2958.2000.01772.x. DOI: https://doi.org/10.1046/j.1365-2958.2000.01772.x
Lostroh, C. P., Bajaj, V., & Lee, C. A. (2000). The cis requirements for transcriptional activation by HilA, a virulence determinant encoded on SPI-1. Molecular microbiology, 37(2), 300–315. https://doi.org/10.1046/j.1365-2958.2000.01991.x. DOI: https://doi.org/10.1046/j.1365-2958.2000.01991.x
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