Abstract
We studied the role of glycolysis in the mechanism of cAMP receptor protein-induced macrophage cell death of Salmonella enterica serovar Typhimurium (S. Typhimurium). Cell apoptosis, caspase-3, -8, -9 enzyme activity, and pyruvic acid, lactic acid, ATP, and hexokinase (HK) contents were determined after infection of macrophages with S. Typhimurium SL1344 wild-type and a cAMP receptor protein mutant strain. While cell apoptosis, caspase-3, -8, -9 enzyme activity, lactic acid, hexokinase, and ATP levels significantly changed by infection with crp mutants compared to the wild-type strain (P < 0.05). Our data suggest that the cAMP receptor protein of S. Typhimurium can modulate macrophage death by effecting glycolysis levels. This finding may help to elucidate the mechanisms of S. Typhimurium pathogenesis.
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References
Wang M, Feng P, Chen X, Zhang H, Ni B, Xie X, Du H (2014) YgaE regulates out membrane proteins in Salmonella enterica serovar Typhi under hyperosmotic stress. Sci World J 2014:374276
Detweiler CS, Cunanan DB, Falkow S (2001) Host microarray analysis reveals a role for the Salmonella response regulator phoP in human macrophage cell death. Proc Natl Acad Sci USA 98(10):5850–5855
Vazquez-Torres A, Jones-Carson J, Baumler AJ, Falkow S, Valdivia R, Brown W, Le M, Berggren R, Parks WT, Fang FC (1999) Extraintestinal dissemination of Salmonella by CD18-expressing phagocytes. Nature 401(6755):804–808
Bacci G, Capanna R, Orlandi M, Mancini I, Bettelli G, Dallari D, Campanacci M (1985) Prognostic significance of serum lactic acid dehydrogenase in Ewing’s tumor of bone. La Ric Clin Lab 15(1):89–96
Hernandez LD, Pypaert M, Flavell RA, Galan JE (2003) A Salmonella protein causes macrophage cell death by inducing autophagy. J Cell Biol 163(5):1123–1131
Santos RL, Tsolis RM, Baumler AJ, Smith R 3rd, Adams LG (2001) Salmonella enterica serovar Typhimurium induces cell death in bovine monocyte-derived macrophages by early sipB-dependent and delayed sipB-independent mechanisms. Infect Immun 69(4):2293–2301
Wijburg OL, Van Rooijen N, Strugnell RA (2002) Induction of CD8+ T lymphocytes by Salmonella Typhimurium is independent of Salmonella pathogenicity island 1-mediated host cell death. J Immunol 169(6):3275–3283
Huang SW, Kao JK, Wu CY, Wang ST, Lee HC, Liang SM, Chen YJ, Shieh JJ (2014) Targeting aerobic glycolysis and HIF-1alpha expression enhance imiquimod-induced apoptosis in cancer cells. Oncotarget 5(5):1363–1381
Kok SH, Hou KL, Hong CY, Chao LH, Hsiang-Hua Lai E, Wang HW, Yang H, Shun CT, Wang JS, Lin SK (2015) Sirtuin 6 modulates hypoxia-induced apoptosis in osteoblasts via inhibition of glycolysis: implication for pathogenesis of periapical lesions. J Endodont 41(10):1631–1637
Liu Y, Tong L, Luo Y, Li X, Chen G, Wang Y (2018) Resveratrol inhibits the proliferation and induces the apoptosis in ovarian cancer cells via inhibiting glycolysis and targeting AMPK/mTOR signaling pathway. J Cell Biochem 119(7):6162–6172
Zhou J, Li C, Yao W, Ma A, Huo L, Liu H, Miao YL (2018) Hypoxia-inducible factor-1alpha-dependent autophagy plays a role in glycolysis switch in mouse granulosa cells. Biol Reprod 99(2):308–318
Hui L, Zhang J, Guo X (2018) MiR-125b-5p suppressed the glycolysis of laryngeal squamous cell carcinoma by down-regulating hexokinase-2. Biomed Pharmacother 103:1194–1201
Sanman LE, Qian Y, Eisele NA, Ng TM, van der Linden WA, Monack DM, Weerapana E, Bogyo M (2016) Disruption of glycolytic flux is a signal for inflammasome signaling and pyroptotic cell death. eLife 5:e13663
Bowden SD, Rowley G, Hinton JC, Thompson A (2009) Glucose and glycolysis are required for the successful infection of macrophages and mice by Salmonella enterica serovar Typhimurium. Infect Immun 77(7):3117–3126
Murphy JN, Durbin KJ, Saltikov CW (2009) Functional roles of arcA, etrA, cyclic AMP (cAMP)-cAMP receptor protein, and cya in the arsenate respiration pathway in Shewanella sp. strain ANA-3. J Bacteriol 191(3):1035–1043
Shimada T, Fujita N, Yamamoto K, Ishihama A (2011) Novel roles of cAMP receptor protein (CRP) in regulation of transport and metabolism of carbon sources. PLoS ONE 6(6):e20081
Basak S, Geng H, Jiang R (2014) Rewiring global regulator cAMP receptor protein (CRP) to improve E. coli tolerance towards low pH. J Biotechnol 173:68–75
Huang L, Pu Y, Yang X, Zhu X, Cai J, Xu Z (2015) Engineering of global regulator cAMP receptor protein (CRP) in Escherichia coli for improved lycopene production. J Biotechnol 199:55–61
Basak S, Jiang R. Enhancing (2012) E. coli tolerance towards oxidative stress via engineering its global regulator cAMP receptor protein (CRP). PLoS ONE 7(12):e51179
Chen ZW, Hsuan SL, Liao JW, Chen TH, Wu CM, Lee WC, Lin CC, Liao CM, Yeh KS, Winton JR, Huang C, Chien MS (2010) Mutations in the Salmonella enterica serovar Choleraesuis cAMP-receptor protein gene lead to functional defects in the SPI-1 Type III secretion system. Vet Res 41(1):5
Chen S, Zhang C, Liao C, Li J, Yu C, Cheng X, Yu Z, Zhang M, Wang Y (2015) Deletion of invasion protein B in Salmonella enterica serovar Typhimurium influences bacterial invasion and virulence. Curr Microbiol 71(6):687–692
Liao C, Cheng X, Zhao Z, Zhang C, Li Y, Wu T, Yu C, Wang X, Hu A (2011) Construction and characterzation of the cAMP receptor protein gene deletion mutant of Salmoella Typhimurium SL1344 strain. Chin J Vet Sci 31(12):1711–1716
Zhang H, Huang Y, Du Q, Luo X, Zhang L, Zhao X, Tong D (2015) Porcine parvovirus infection induces apoptosis in PK-15 cells through activation of p53 and mitochondria-mediated pathway. Biochem Biophys Res Commun 456(2):649–655
Berger AK, Danthi P (2013) Reovirus activates a caspase-independent cell death pathway. mBio 4(3):e00178–e00113
Ding L, Huang Y, Du Q, Dong F, Zhao X, Zhang W, Xu X, Tong D (2014) TGEV nucleocapsid protein induces cell cycle arrest and apoptosis through activation of p53 signaling. Biochem Biophys Res Commun 445(2):497–503
Akhter Y, Yellaboina S, Farhana A, Ranjan A, Ahmed N, Hasnain SE (2008) Genome scale portrait of cAMP-receptor protein (CRP) regulons in mycobacteria points to their role in pathogenesis. Gene 407(1–2):148–158
Xue J, Tan B, Yang S, Luo M, Xia H, Zhang X, Zhou X, Yang X, Yang R, Li Y, Qiu J (2016) Influence of cAMP receptor protein (CRP) on bacterial virulence and transcriptional regulation of allS by CRP in Klebsiella pneumoniae. Gene 593(1):28–33
Cook P, Totemeyer S, Stevenson C, Fitzgerald KA, Yamamoto M, Akira S, Maskell DJ, Bryant CE (2007) Salmonella-induced SipB-independent cell death requires Toll-like receptor-4 signalling via the adapter proteins Tram and Trif. Immunology 122(2):222–229
Gunster RA, Matthews SA, Holden DW, Thurston TL (2017) SseK1 and SseK3 type III secretion system effectors inhibit NF-kappaB signaling and necroptotic cell death in Salmonella-infected macrophages. Infect Immun 85(3):IAI-00010
He P, Wu S, Chu Y, Yang Y, Li Y, Huang R (2012) Salmonella enterica serovar Typhi plasmid pR ST98 enhances intracellular bacterial growth and S. typhi-induced macrophage cell death by suppressing autophagy. Braz J Infect Dis 16(3):262–266
Kurita A, Gotoh H, Eguchi M, Okada N, Matsuura S, Matsui H, Danbara H, Kikuchi Y (2003) Intracellular expression of the Salmonella plasmid virulence protein, SpvB, causes apoptotic cell death in eukaryotic cells. Microb Pathog 35(1):43–48
Thurston TL, Matthews SA, Jennings E, Alix E, Shao F, Shenoy AR, Birrell MA, Holden DW (2016) Growth inhibition of cytosolic Salmonella by caspase-1 and caspase-11 precedes host cell death. Nat Commun 7:13292
Ou Q, Fan J, Duan D, Xu L, Wang J, Zhou D, Yang H, Li B (2017) Involvement of cAMP receptor protein in biofilm formation, fimbria production, capsular polysaccharide biosynthesis and lethality in mouse of Klebsiella pneumoniae serotype K1 causing pyogenic liver abscess. J Med Microbiol 66(1):1–7
Zhao X, Liu Q, Xiao K, Hu Y, Liu X, Li Y, Kong Q (2016) Identification of the crp gene in avian Pasteurella multocida and evaluation of the effects of crp deletion on its phenotype, virulence and immunogenicity. BMC Microbiol 16(1):125
Zhu Y, Ramos da Silva S, He M, Liang Q, Lu C, Feng P, Jung JU, Gao SJ (2016) An oncogenic virus promotes cell survival and cellular transformation by suppressing glycolysis. PLoS Pathog 12(5):e1005648
Tchawa Yimga M, Leatham MP, Allen JH, Laux DC, Conway T, Cohen PS (2006) Role of gluconeogenesis and the tricarboxylic acid cycle in the virulence of Salmonella enterica serovar Typhimurium in BALB/c mice. Infect Immun 74(2):1130–1140
Hos NJ, Ganesan R, Gutierrez S, Hos D, Klimek J, Abdullah Z, Kronke M, Robinson N (2017) Type I interferon enhances necroptosis of Salmonella Typhimurium-infected macrophages by impairing antioxidative stress responses. J Cell Biol 216(12):4107–4121
Acknowledgements
This study was supported by grants from the National Natural Science Foundation of China (Grant 31572489), the HeNan Natural Science Foundation (182300410078), and the National Key R&D Program (2016YFD0500708).
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Ding, K., Zhang, C., Li, J. et al. cAMP Receptor Protein of Salmonella enterica Serovar Typhimurium Modulate Glycolysis in Macrophages to Induce Cell Apoptosis. Curr Microbiol 76, 1–6 (2019). https://doi.org/10.1007/s00284-018-1574-1
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DOI: https://doi.org/10.1007/s00284-018-1574-1