Abstract
Unsuccessful vaccination against Salmonella due to a large number of serovars, and antibiotic resistance, necessitates the development of novel therapeutics to treat salmonellosis. The development of anti-virulence agents against multi-drug-resistant bacteria is a novel strategy because of its non-bacterial feature. Hence, a thorough study of the type three secretion system (T3SS) of Salmonella would help us better understand its role in bacterial pathogenesis and development of anti-virulence agents. However, T3SS can be inhibited by different chemicals at different stages of infection and sequenced delivery of effectors can be blocked to restrict the progression of disease. This review highlights the role of T3SS-1 in the internalization, survival, and replication of Salmonella within the intestinal epithelium and T3SS inhibitors. We concluded that the better we understand the structures and functions of T3SS, the more we have chances to develop anti-virulence agents. Furthermore, greater insights into the T3SS inhibitors of Salmonella would help in the mitigation of the antibiotic resistance problem and would lead us to the era of new therapeutics against salmonellosis.
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Akeda Y, Galán JE (2005) Chaperone release and unfolding of substrates in type III secretion. Nature 437:911
Alemán A, Rodríguez-Escudero I, Mallo GV, Cid VJ, Rotger R (2010) The amino-terminal non-catalytic region of Salmonella typhimurium SigD affects actin organization in yeast and mammalian cells. Cell Microbiol 7:1432–1446
Antillón M, Warren JL, Crawford FW, Weinberger DM, Kürüm E, Pak GD, Marks F, Pitzer VE (2017) The burden of typhoid fever in low-and middle-income countries: A meta-regression approach. PLoS Negl Trop Dis 11:e0005376
Babich H, Zuckerbraun HL, Barber IB, Babich SB, Borenfreund E (1996) Cytotoxicity of sanguinarine chloride to cultured human cells from oral tissue. Pharmacol Toxicol 78:397–403
Bakowski MA, Cirulis JT, Brown NF, Finlay BB, Brumell JH (2007a) SopD acts cooperatively with SopB during Salmonella enterica serovar Typhimurium invasion. Cell Microbiol 9:2839–2855
Bakowski MA, Cirulis JT, Brown NF, Finlay BB, Brumell JH (2007b) SopD acts cooperatively with SopB during Salmonella enterica serovar Typhimurium invasion. Cell Microbiol 9:2839–2855
Bakshi C, Singh V, Wood M, Jones P, Wallis T, Galyov E (2000) Identification of SopE2, a Salmonella secreted protein which is highly homologous to SopE and involved in bacterial invasion of epithelial cells. J Bacteriol 182:2341–2344
Baron C, Coombes B (2007) Targeting bacterial secretion systems: benefits of disarmament in the microcosm. Infect Disord Drug Targets 7:19–27
Bergeron J, Fernández L, Wasney GA, Vuckovic M, Reffuveille F, Hancock R, Strynadka N (2016) The structure of a type 3 secretion system (T3SS) ruler protein suggests a molecular mechanism for needle length sensing *. J Biol Chem 291:1676–1691
Boucher HW, Ambrose PG, Chambers HF, Ebright RH, Jezek A, Murray BE, Newland JG, Ostrowsky B, Rex JH, Infectious Diseases Society of A (2017) White paper: developing antimicrobial drugs for resistant pathogens, narrow-spectrum indications, and unmet needs. J Infect Dis 216:228–236
Boyle EC, Brown NF, Finlay BB (2006) Salmonella enterica serovar Typhimurium effectors SopB, SopE, SopE2 and SipA disrupt tight junction structure and function. Cell Microbiol 8:1946–1957
Braun V, Wong A, Landekic M, Hong WJ, Grinstein S, Brumell JH (2010) Sorting nexin 3 (SNX3) is a component of a tubular endosomal network induced by Salmonella and involved in maturation of the Salmonella-containing vacuole. Cell Microbiol 12:1352–1367
Brawn LC, Hayward RD, Koronakis V (2007) Salmonella SPI1 effector SipA persists after entry and cooperates with a SPI2 effector to regulate phagosome maturation and intracellular replication. Cell Host Microbe 1:63–75
Carlson SA, Omary MB, Jones BD (2002) Identification of cytokeratins as accessory mediators of Salmonella entry into eukaryotic cells. Life Sci 70:1415–1426
Chatterjee S, Chaudhury S, McShan AC, Kaur K, De Guzman RN (2013) Structure and biophysics of type III secretion in bacteria. Biochemistry 52(15):2508–2517
Chen S-H, Parker CH, Croley TR, McFarland MA (2019) Identification of Salmonella taxon-specific peptide markers to the serovar level by mass spectrometry. Anal Chem 91:4388–4395
Choi HW, Brooking-Dixon R, Neupane S, Lee C-J, Miao EA, Staats HF, Abraham SN (2013) Salmonella typhimurium impedes innate immunity with a mast-cell-suppressing protein tyrosine phosphatase, SptP. Immun 39:1108–1120
Cohen ML (1992) Epidemiology of drug resistance: implications for a post-antimicrobial era. Sci 257:1050–1055
Cornelis GR, Wolf-watz H (2010) The Yersinia Yop virulon: a bacterial system for subverting eukaryotic cells. Mol Microbiol 23
Corrotte M, Nyguyen AP, Harlay ML, Vitale N, Bader MF, Grant NJ (2010) Ral isoforms are implicated in Fc gamma R-mediated phagocytosis: activation of phospholipase D by RalA. J Immunol 185:2942–2950
Criss AK, Silva M, Casanova JE, McCormick BA (2001) Regulation of Salmonella-induced neutrophil transmigration by epithelial ADP-ribosylation factor 6 *. J Biol Chem 276:48431–48439
Crutcher FK, Puckhaber LS, Stipanovic RD, Bell AA, Liu J (2017) Microbial resistance mechanisms to the antibiotic and phytotoxin fusaric acid. J Chem Ecol 43:1–11
Deepak S, Ruchi S, Sandra C, Alvaro V (2016) Myricetin: a dietary molecule with diverse biological activities. Nutrients 8:90
Deng W, Marshall NC, Rowland JL, McCoy JM, Worrall LJ, Santos AS, Strynadka NC, Finlay BB (2017) Assembly, structure, function and regulation of type III secretion systems. Nat Rev Microbiol 15:323
Desvaux M, Hébraud M, Henderson IR, Pallen MJ (2006) Type III secretion: what’s in a name? Trends Microbiol 14:157–160
Diepold A, Wagner S (2014) Assembly of the bacterial type III secretion machinery. FEMS Microbiol Rev 38(4):802–822
Dreher D, Kok M, Obregon C, Kiama SG, Gehr P, Nicod LP (2002) Salmonella virulence factor SipB induces activation and release of IL-18 in human dendritic cells. J Leukoc Biol 72:743–751
Ehrbar K, Hapfelmeier S, Stecher B, Hardt W-D (2004) InvB is required for type III-dependent secretion of SopA in Salmonella enterica serovar Typhimurium. J Bacteriol 186:1215–1219
Engel AC, Herbst F, Kerres A, Galle JN, Hegemann JH (2016) The type III secretion system-related CPn0809 from Chlamydia pneumoniae. PloS One 11:e0148509
Felise HB, Nguyen HV, Pfuetzner RA, Barry KC, Jackson SR, Blanc M-P, Bronstein PA, Kline T, Miller SI (2008) An inhibitor of gram-negative bacterial virulence protein secretion. Cell Host Microbe 4:325–336
Fiskin E, Bhogaraju S, Herhaus L, Kalayil S, Hahn M, Dikic I (2017) Structural basis for the recognition and degradation of host TRIM proteins by Salmonella effector SopA. Nat Commun 8:14004
Forsberg A, Wolf-Watz H (2006) The virulence protein Yop5 of Yersinia pseudotuberculosis is regulated at transcriptional level by plasmid-plB1 -encoded trans\n-acting elements controlled by temperature and calcium. Mol Microbiol 2:121–133
Foultier B, Troisfontaines P, Müller S, Opperdoes FR, Cornelis GR (2002) Characterization of the ysa pathogenicity locus in the chromosome of Yersinia enterocolitica and phylogeny analysis of type III secretion systems. J Mol Evol 55:37–51
Friebel A, Ilchmann H, Aepfelbacher M, Ehrbar K, Machleidt W, Hardt WD (2001) SopE and SopE2 from Salmonella typhimurium activate different sets of RhoGTPases of the host cell. J Biol Chem 276:34035
Fu Y, Galán JE (1998a) The Salmonella typhimurium tyrosine phosphatase SptP is translocated into host cells and disrupts the actin cytoskeleton. Mol Microbiol 27:359–368
Fu Y, Galán JE (1999) A Salmonella protein antagonizes Rac-1 and Cdc42 to mediate host-cell recovery after bacterial invasion. Nature 401:293
Fu YX, Galán J (1998b) Identification of a specific chaperone for SptP, a substrate of the centisome 63 type III secretion system of Salmonella typhimurium. J Bacteriol 180:3393–3399
Galán JE, Wolf-Watz H (2006) Protein delivery into eukaryotic cells by type III secretion machines. Nature 444:567
Galán JE (2009) Common themes in the design and function of bacterial effectors. Cell Host Microbe 5:571–579
Galán JE, Lara-Tejero M, Marlovits TC, Wagner S (2014) Bacterial type III secretion systems: specialized nanomachines for protein delivery into target cells. Annu Rev Microbiol 68:415–438
Galyov EE, Wood MW, Rosqvist R, Mullan PB, Watson PR, Hedges S, Wallis TS (1997) A secreted effector protein of Salmonella dublin is translocated into eukaryotic cells and mediates inflammation and fluid secretion in infected ileal mucosa. Mol Microbiol 25:903–912
García-Gil A, Galán-Enríquez CS, Pérez-López A, Nava P, Alpuche-Aranda C, Ortiz-Navarrete V (2018) SopB activates the Akt-YAP pathway to promote Salmonella survival within B cells. Virulence 9:1390–1402
Ghannadi A, Sajjadi SE, Kabouche A (2004) Thymus fontanesii Boiss. & Reut.-A potential source of thymol-rich essential oil in North Africa. Zeitschrift für Naturforschung C 59(3–4):187–189
Gibbs KD, Washington EJ, Jaslow SL, Bourgeois JS, Foster MW, Guo R, Ko DC (2020) The Salmonella Secreted Effector SarA/SteE Mimics Cytokine Receptor Signaling to Activate STAT3. Cell Host Microbe 27(1):129–139
Glasgow AA, Wong HT, Tullman-Ercek D (2017) A secretion-amplification role for Salmonella enterica Translocon protein SipD. ACS Synth Biol 6:1006–1015
Guo Z, Li X, Li J, Yang X, Zhou Y, Lu C, Shen Y (2016) Licoflavonol is an inhibitor of the type three secretion system of Salmonella enterica serovar Typhimurium. Biochem Biophys Res Commun 477:998–1004
Hapfelmeier S, Stecher B, Barthel M, Kremer M, Müller AJ, Heikenwalder M, Stallmach T, Hensel M, Pfeffer K, Akira S (2005) The Salmonella pathogenicity island (SPI)-2 and SPI-1 type III secretion systems allow Salmonella serovar typhimurium to trigger colitis via MyD88-dependent and MyD88-independent mechanisms. J Immunol 174:1675–1685
Hardt WD, Galán JE (1997) A secreted Salmonella protein with homology to an avirulence determinant of plant pathogenic bacteria. Proc National Acad Sci 94(18):9887–9892
Hardt WD, Galan U (1998) A substrate of the centisome 63 type III protein secretion system of Salmonella typhimurium is encoded by a cryptic bacteriophage. Proc Natl Acad Sci 95:2574–2579
Hauser AR (2009) The type III secretion system of Pseudomonas aeruginosa: infection by injection. Nat Rev Microbiol 7:654–665
Hayward RD (1999) Direct nucleation and bundling of actin by the SipC protein of invasive Salmonella. Embo J 18:4926–4934
Hayward RD, Koronakiss V (2002) Direct modulation of the host cell cytoskeleton by Salmonella actin-binding proteins. Trends Cell Biol 12:15–20
He H, Lei Z, Xiaodong Z, Xun J, Xiao D (2010) Total synthesis of cytosporone B. Chin J Chem 28:1041–1043
Hersh D, Monack DM, Smith MR, Ghori N, Falkow S, Zychlinsky A (1999) The Salmonella invasin SipB induces macrophage apoptosis by binding to caspase-1. Proc Natl Acad Sci 96:2396–2401
Hong KH, Miller VL (1998) Identification of a novel Salmonella invasion locus homologous to Shigella ipgDE. J Bacteriol 180:1793
Hu B, Lara-Tejero M, Kong Q, Galán J, Liu J (2017) In situ molecular architecture of the salmonella type III secretion machine. Cell 168:1065–1074
Hudson DL, Layton AN, Field TR, Bowen AJ, Wolf-Watz H, Elofsson M, Stevens MP, Galyov EE (2007) Inhibition of type III secretion in Salmonella enterica serovar Typhimurium by small-molecule inhibitors. Antimicrob Agents Chemother 51:2631–2635
Jantsch J, Chikkaballi D, Hensel M (2011) Cellular aspects of immunity to intracellular Salmonella enterica. Immunol Rev 240:185–195
Johnson R, Byrne A, Berger CN, Klemm E, Crepin VF, Dougan G, Frankel G (2017) The type III secretion system effector SptP of Salmonella enterica serovar Typhi. J Bacteriol 199:e00647–e00616
Johnson R, Mylona E, Frankel G (2018) Typhoidal Salmonella: distinctive virulence factors and pathogenesis. Cell Microbiol 20:e12939
Kaniga K, Tucker S, Trollinger D, Galan JE (1995) Homologs of the Shigella IpaB and IpaC invasins are required for Salmonella typhimurium entry into cultured epithelial cells. J Bacteriol 177:3965–3971
Kaniga K, Uralil J, Bliska JB, Galán JE (1996) A secreted protein tyrosine phosphatase with modular effector domains in the bacterial pathogen Salmonella typhimurlum. Mol Microbiol 21:633–641
Kaur K, Chatterjee S, Deguzman RN (2016) Characterization of the Shigella and Salmonella typeIII secretion system tip–translocon protein–protein interaction by paramagnetic relaxation enhancement. Chembiochem A Eur J Chem Biol 17
Kawakami T, Ando T (2013) Salmonella’s masterful skill in mast cell suppression. Immunity 39:996–998
Kenney LJ (2019) The role of acid stress in Salmonella pathogenesis. Curr Opin Microbiol 47:45–51
Kline T, Felise HB, Barry KC, Jackson SR, Nguyen HV, Miller SI (2008) Substituted 2-imino-5-arylidenethiazolidin-4-one inhibitors of bacterial type III secretion. J Med Chem 51:7065–7074
Kubori T (1998) Supramolecular Structure of the Salmonella typhimurium type III protein secretion system. Sci 280:602–605
Kubori T, Sukhan A, Aizawa S-I, Galán JE (2000) Molecular characterization and assembly of the needle complex of the Salmonella typhimurium type III protein secretion system. Proc Natl Acad Sci 97:10225–10230
Lara-Tejero M, Galán JE (2009) Salmonella enterica serovar typhimurium pathogenicity island 1-encoded type III secretion system translocases mediate intimate attachment to nonphagocytic cells. Infect Immun 77:2635–2642
Lara-Tejero M, Kato J, Wagner S, Liu X, Galán JE (2011) A sorting platform determines the order of protein secretion in bacterial type III systems. Sci 331:1188–1191
Lara-Tejero M, Qin Z, Hu B, Butan C, Liu J, Galán JE (2019) Role of SpaO in the assembly of the sorting platform of a Salmonella type III secretion system. PLoS Pathog 15:e1007565
Lau N, Haeberle AL, O'Keeffe BJ, Latomanski EA, Celli J, Newton HJ, Knodler LA (2019) SopF, a phosphoinositide binding effector, promotes the stability of the nascent Salmonella-containing vacuole. PLoS Pathog
Layton AN, Hudson DL, Thompson A, Hinton JC, Stevens JM, Galyov EE, Stevens MP (2010) Salicylidene acylhydrazide-mediated inhibition of type III secretion system-1 in Salmonella enterica serovar Typhimurium is associated with iron restriction and can be reversed by free iron. FEMS Microbiol Lett 302:114–122
Lee CA, Silva M, Siber AM, Kelly AJ, Galyov E, McCormick BA (2000) A secreted Salmonella protein induces a proinflammatory response in epithelial cells, which promotes neutrophil migration. Proc Natl Acad Sci 97:12283–12288
Lee SO, Li X, Khan S, Safe S (2011) Targeting NR4A1 (TR3) in cancer cells and tumors. Expert Opin Ther Targets 15:195–206
Levy SB (1998) The challenge of antibiotic resistance. Sci Am 278:46
Lhocine N, Arena ET, Bomme P, Ubelmann F, Prévost M-C, Robine S, Sansonetti PJ (2015) Apical invasion of intestinal epithelial cells by Salmonella typhimurium requires villin to remodel the brush border actin cytoskeleton. Cell Host Microbe 17:164–177
Li J, Lv C, Sun W, Li Z, Han X, Li Y, Shen Y (2013) Cytosporone B, an inhibitor of the type III secretion system of Salmonella enterica serovar Typhimurium. Antimicrob Agents Chemother 57:2191–2198
Li J, Sun W, Guo Z, Lu C, Shen Y (2014) Fusaric acid modulates type three secretion system of Salmonella enterica serovar Typhimurium. Biochem Biophys Res Commun 449:455–459
Lie ML, Calkin VLE, Orlova A, Vanloock MS, Egelman EH, Er C (2003) Salmonella SipA polymerizes actin by stapling filaments with nonglobular protein arms. Sci 301:1918–1921
Liu Y, Zhang Y, Zhou Y, Wang T, Zhou T (2019) Cinnamaldehyde inhibits type three secretion system in Salmonella enterica serovar Typhimurium by affecting the expression of key effector proteins. Vet Microbiol 239:108463
Lostroh CP, Lee CA (2001) The Salmonella pathogenicity island-1 type III secretion system. Microbes Infect 3:1281–1291
Lu R, Wu S, Y-g Z, Xia Y, Zhou Z, Kato I, Dong H, Bissonnette M, Sun J (2016) Salmonella protein AvrA activates the STAT3 signaling pathway in colon cancer. Neoplasia 18:307–316
Lunelli M, Hurwitz R, Lambers J, Kolbe M (2011) Crystal structure of PrgI-SipD: insight into a secretion competent state of the type three secretion system needle tip and its interaction with host ligands. PLoS Pathog 7:e1002163
Lv Q, Chu X, Yao X, Ma K, Zhang Y, Deng X (2019) Inhibition of the type III secretion system by syringaldehyde protects mice from Salmonella enterica serovar Typhimurium. J Cell Mol Med 23(7):4679–4688
Lv Q, Li S, Wei H, Wen Z, Wang Y, Tang T, Deng X (2020) Identification of the natural product paeonol derived from peony bark as an inhibitor of the Salmonella enterica serovar Typhimurium type III secretion system. Appl Microbiol Biotechnol 104(4):1673–1682
Lv Q, Lv Y, Dou X, Wassy SL, Wang J (2021) Myricetin inhibits the type III secretion system of Salmonella enterica serovar typhimurium by downregulating the Salmonella pathogenic island I gene regulatory pathway. Microb Pathog 150:104695
Mahmud MS, Bari ML, Hossain MA (2011) Prevalence of Salmonella serovars and antimicrobial resistance profiles in poultry of Savar Area, Bangladesh. Foodborne Pathog Dis 8:1111–1118
Majowicz SE, Musto J, Scallan E, Angulo FJ, Kirk M, O'Brien SJ, Jones TF, Fazil A, Hoekstra RM, Studies ICoEDBoI (2010) The global burden of nontyphoidal Salmonella gastroenteritis. Clin Infect Dis 50:882–889
Malik-Kale P, Jolly CE, Lathrop S, Winfree S, Luterbach C, Steele-Mortimer O (2011) Salmonella – at home in the host cell. Front Microbiol 2:125
Marcus SL, Wenk MR, Steele-Mortimer O, Finlay BB (2001) A synaptojanin-homologous region of Salmonella typhimurium SigD is essential for inositol phosphatase activity and Akt activation. FEBS Lett 494(3):201–207
Marlovits TC, Kubori T, Sukhan A, Thomas DR, Galán JE, Unger VM (2004) Structural insights into the assembly of the type III secretion needle complex. Sci 306:1040–1042
Maserati A, Fink RC, Lourenco A, Julius ML, Diez-Gonzalez F (2017) General response of Salmonella enterica serovar Typhimurium to desiccation: a new role for the virulence factors sopD and sseD in survival. PloS One 12:e0187692
Rhen M, Mastroeni P, Threlfall J (Eds.). (2007) Salmonella: molecular biology and pathogenesis. Horizon Scientific Press.
Matsuda S, Haneda T, Saito H, Miki T, Okada N (2019) Salmonella enterica Effectors SifA, SpvB, SseF, SseJ, and SteA contribute to type III secretion system 1-independent inflammation in a streptomycin-pretreated mouse model of colitis. Infect Immun. 87:e00872–18. doi: 10.1128/IAI.00872-18
Mccormick BA, Parkos CA, Colgan SP, Carnes DK, Madara JL (1998) Apical secretion of a pathogen-elicited epithelial chemoattractant activity in response to surface colonization of intestinal epithelia by Salmonella typhimurium. J Immunol 160:455–466
Mcghie EJ, Hayward RD, Koronakis V (2004) Control of actin turnover by a salmonella invasion protein. Mol Cell 13:497–510
Mcghie EJ, Brawn LC, Hume PJ, Humphreys D, Koronakis V (2009) Salmonella takes control: effector-driven manipulation of the host. Curr Opin Microbiol 12:117–124
Mcghie EJ, Hayward RD, Koronakis V (2014) Cooperation between actin-binding proteins of invasive Salmonella: SipA potentiates SipC nucleation and bundling of actin. Embo J 20:2131–2139
McShan AC, Anbanandam A, Patnaik S, De Guzman RN (2016) Characterization of the binding of hydroxyindole, indoleacetic acid, and morpholinoaniline to the salmonella type III secretion system proteins SipD and SipB. ChemMedChem 11:963–971
Meehl MA, Caparon MG (2010) Specificity of streptolysin O in cytolysin-mediated translocation. Mol Microbiol 52:1665–1676
Mirold S, Rabsch W, Rohde M, Stender S, Tschape H, Russmann H, Igwe E, Hardt WD (1999) Isolation of a temperate bacteriophage encoding the type III effector protein SopE from an epidemic Salmonella typhimurium strain. Proc Natl Acad Sci
Mondal A, Gandhi A, Fimognari C, Atanasov AG, Bishayee A (2019) Alkaloids for cancer prevention and therapy: current progress and future perspectives. Eur J Pharmacol 858:172472
Murli S, Watson RO, Galán J (2001) Role of tyrosine kinases and the tyrosine phosphatase SptP in the interaction of Salmonella with host cells. Cell Microbiol 3:795–810
Negrea A, Bjur E, Ygberg SE, Elofsson M, Wolf-Watz H, Rhen M (2007) Salicylidene acylhydrazides that affect type III protein secretion in Salmonella enterica serovar typhimurium. Antimicrob Agents Chemother 51:2867–2876
Nichols C, Casanova JE (2010) Salmonella-directed recruitment of new membrane to invasion foci via the host exocyst complex. Curr Biol 20:1316–1320
Nordfelth R, Kauppi AM, Norberg HA, Wolf-Watz H, Elofsson M (2005) Small-molecule inhibitors specifically targeting type III secretion. Infect Immun 73:3104–3114
Notti RQ, Stebbins CE (2016) The structure and function of type III secretion systems. Virulence Mechanisms of Bacterial Pathogens, 241-264.
Obregon C, Dreher D, Kok M, Cochand L, Kiama GS, Nicod LP (2003) Human alveolar macrophages infected by virulent bacteria expressing SipB are a major source of active interleukin-18. Infect Immun 71:4382–4388
Pickard D, Wain J, Baker S, Line A, Chohan S, Fookes M, Barron A, Gaora PÓ, Chabalgoity JA, Thanky N (2003) Composition, acquisition, and distribution of the Vi exopolysaccharide-encoding Salmonella enterica pathogenicity island SPI-7. J Bacteriol 185:5055–5065
Pilar AVC, Reid-Yu SA, Cooper CA, Mulder DT, Coombes BK (2012) GogB is an anti-inflammatory effector that limits tissue damage during Salmonella infection through interaction with human FBXO22 and Skp1. PLoS Pathog 8:e1002773
Raffatellu M, Wilson RP, Chessa D, Andrews-Polymenis H, Tran QT, Lawhon S, Khare S, Adams LG, Bäumler AJ (2005) SipA, SopA, SopB, SopD, and SopE2 contribute to Salmonella enterica serotype Typhimurium invasion of epithelial cells. Infect Immun 73:146–154
Ramos-Morales F (2013, 2012) Impact of Salmonella enterica type III secretion system effectors on the eukaryotic host cell. Isrn Cell Biology:787934
Rao S, Schieber AMP, O’Connor CP, Leblanc M, Michel D, Ayres JS (2017) Pathogen-mediated inhibition of anorexia promotes host survival and transmission. Cell 168(e12):503–516
Rasko DA, Sperandio V (2010) Anti-virulence strategies to combat bacteria-mediated disease. Nat Rev Drug Discov 9:117–128
Rathinavelan T, Lara-Tejero M, Lefebre M, Chatterjee S, McShan AC, Guo DC, De Guzman RN (2014) NMR model of PrgI–sipd interaction and its implications in the needle-tip assembly of the Salmonella type III secretion system. J Molecular Bio 426(16):2958–2969
Raucher D, Stauffer T, Wen C, Kang S, Guo S, York JD, Sheetz MP, Meyer T (2000) Phosphatidylinositol 4,5-bisphosphate functions as a second messenger that regulates cytoskeleton–plasma membrane adhesion. Cell 100:221–228
Reveglia P, Cinelli T, Cimmino A, Masi M, Evidente A (2018) The main phytotoxic metabolite produced by a strain of Fusarium oxysporum inducing grapevine plant declining in Italy. Nat Prod Res
Robertson J, Yoshida C, Gurnik S, McGrogan M, Davis K, Arya G, Murphy SA, Nichani A, Nash JHE (2018) An improved DNA array-based classification method for the identification of Salmonella serotypes shows high concordance between traditional and genotypic testing. PloS One 13(e0207550):1932–6203
Rudolph MG, Weise C, Mirold S, Hillenbrand B, Bader B, Wittinghofer A, Hardt W-D (1999) Biochemical analysis of SopE from Salmonella typhimurium, a highly efficient guanosine nucleotide exchange factor for RhoGTPases. J Biol Chem 274:30501–30509
Salmond GP, Reeves PJ (1993) Membrane traffic wardens and protein secretion in gram-negative bacteria. Trends Biochem Sci 18:7–12
Scherer CA, Cooper E, Miller SI (2000) The Salmonella type III secretion translocon protein SspC is inserted into the epithelial cell plasma membrane upon infection. Mol Microbiol 37:1133–1145
Schlumberger MC, Hardt W-D (2006a) Salmonella type III secretion effectors: pulling the host cell’s strings. Curr Opin Microbiol 9:46–54
Schlumberger MC, Hardt WD (2006b) Salmonella type III secretion effectors: pulling the host cell’s strings. Curr Opin Microbiol 9:46–54
Schraidt O, Lefebre MD, Brunner MJ, Schmied WH, Schmidt A, Radics J, Mechtler K, Galán JE, Marlovits TC (2010) Topology and organization of the Salmonella typhimurium type III secretion needle complex components. PLoS Pathog 6:e1000824
Sekiya K, Ohishi M, Ogino T, Tamano K, Sasakawa C, Abe A (2001) Supermolecular structure of the enteropathogenic Escherichia coli type III secretion system and its direct interaction with the EspA-sheath-like structure. Proc National Acad Sci 98(20):11638–11643
Stebbins CE, Galán J (2000) Modulation of host signaling by a bacterial mimic: structure of the Salmonella effector SptP bound to Rac1. Mol Cell 6:1449–1460
Steele-Mortimer (2000) Activation of Akt/Protein kinase B in epithelial cells by the Salmonella typhimurium effector SigD. J Biol Chem 275:37718
Swietnicki W, Carmany D, Retford M, Guelta M, Dorsey R, Bozue J, Lee MS, Olson MA (2011) Identification of small-molecule inhibitors of Yersinia pestis type III secretion system YscN ATPase. PLoS One 6:e19716
Tsou LK, Dossa PD, Hang HC (2013) Small molecules aimed at type III secretion systems to inhibit bacterial virulence. MedChemComm 4:68–79
Vonaesch P, Sellin ME, Cardini S, Singh V, Barthel M, Hardt WD (2014) The Salmonella Typhimurium effector protein SopE transiently localizes to the early SCV and contributes to intracellular replication. Cell Microbiol 16:1723–1735
Wang D, Zetterström CE, Gabrielsen M, Beckham KS, Tree JJ, Macdonald SE, Byron O, Mitchell TJ, Gally DL, Herzyk P (2011) Identification of bacterial target proteins for the salicylidene acylhydrazide class of virulence-blocking compounds. J Biol Chem 286:29922–29931
Hardt WD, Chen LM, Schuebel KE, Bustelo XR, Galán JE (1998). S. typhimurium encodes an activator of Rho GTPases that induces membrane ruffling and nuclear responses in host cells. Cell 93(5):815–826
Wood MW, Jones MA, Watson PR, Hedges S, Wallis TS, Galyov EE (1998) Identification of a pathogenicity island required for Salmonella enteropathogenicity. Mol Microbiol 29:883–891
Worrall LJ, Vuckovic M, Strynadka NC (2010a) Crystal structure of the C-terminal domain of the Salmonella type III secretion system export apparatus protein InvA. Protein Sci 19(5):1091–1096
Worrall LJ, Vuckovic M, Strynadka NC (2010b) Crystal structure of the C-terminal domain of the Salmonella type III secretion system export apparatus protein InvA. Protein Sci 19:1091–1096
Xia Z, Cao X, Rico-Bautista E, Yu J, Chen L, Chen J, Bobkov A, Wolf DA, Zhang XK, Dawson MI (2013) Relative impact of 3- and 5-hydroxyl groups of cytosporone B on cancer cell viability. MedChemComm 4:332–339
Xian D, Ning L, Min W, Shen Q, Guo S (2012) Fusaric acid is a crucial factor in the disturbance of leaf water imbalance in Fusarium -infected banana plants. Plant Physiol Biochem 60:171–179
Zhang Y, Higashide W, Dai S, Sherman DM, Zhou D (2005) Recognition and ubiquitination of Salmonella type III effector SopA by a ubiquitin E3 ligase, HsRMA1. J Biol Chem 280:38682–38688
Zhang Y, Liu Y, Qiu J, Luo Z-Q, Deng X (2018a) The herbal compound thymol protects mice from lethal infection by Salmonella Typhimurium. Front Microbiol 9
Zhang Y, Liu Y, Wang T, Deng X, Chu X (2018b) Natural compound sanguinarine chloride targets the type III secretion system of Salmonella enterica Serovar Typhimurium. Biochem Biophys Rep 14:149–154
Zhou D, Mooseker MS, Galán JE (1999a) Role of the S. typhimurium actin-binding protein SipA in bacterial internalization. Science 283(5410):2092–2095
Zhou D, Mooseker MS, Galán JE (1999b) An invasion-associated Salmonella protein modulates the actin-bundling activity of plastin. Proc Natl Acad Sci 96:10176–10181
Zhou D, Chen L, Hernandez L, Shears SB, Galán J (2010) A Salmonella inositol polyphosphatase acts in conjunction with other bacterial effectors to promote host cell actin cytoskeleton rearrangements and bacterial internalization. Mol Microbiol 39
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This study was supported by a project funded by the National Natural Science Foundation of China (31702284) and the Sichuan Agricultural University Shuangzhi Support Planning (grant number 03571815 and 03572452).
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SH and PO wrote and designed the manuscript. ZYK did the graphical work of the manuscript. AK, HCL, and XXL contributed through their intellectual inputs. GS and LZY read and corrected the contents.
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Hussain, S., Ouyang, P., Zhu, Y. et al. Type 3 secretion system 1 of Salmonella typhimurium and its inhibitors: a novel strategy to combat salmonellosis. Environ Sci Pollut Res 28, 34154–34166 (2021). https://doi.org/10.1007/s11356-021-13986-4
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DOI: https://doi.org/10.1007/s11356-021-13986-4