{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T23:10:34Z","timestamp":1788909034530,"version":"build-2803163510"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T00:00:00Z","timestamp":1698969600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"\n Background<\/jats:title>\n \n S<\/jats:italic>\n . Typhi is a Gram-negative bacterium that causes typhoid fever in humans. Its virulence depends on the TolC outer membrane pump, which expels toxic compounds and antibiotics. However, the role of TolC in the host cell adhesion and invasion by\n S<\/jats:italic>\n . Typhi is unclear.\n <\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n \n We aimed to investigate how deleting the\n tolC<\/jats:italic>\n affects the adhesion and invasion of HT-29 epithelial and THP-1 macrophage cells by\n S<\/jats:italic>\n . Typhi\n in vitro<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We compared the adhesion and invasion rates of the wild-type and the\n tolC<\/jats:italic>\n mutant strains of\n S<\/jats:italic>\n . Typhi using in vitro adhesion and invasion assays. We also measured the expression levels of SPI-1 genes (\n invF, sipA<\/jats:italic>\n ,\n sipC<\/jats:italic>\n , and\n sipD<\/jats:italic>\n ) using quantitative PCR.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n We found that the\n tolC<\/jats:italic>\n mutant showed a significant reduction in adhesion and invasion compared to the wild-type strain in both cell types. We also observed that the expression of SPI-1 genes was downregulated in the\n tolC<\/jats:italic>\n mutant.\n <\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n \n Our results suggest that TolC modulates the expression of SPI-1 genes and facilitates the adhesion and invasion of host cells by\n S<\/jats:italic>\n . Typhi. Our study provides new insights into the molecular mechanisms of\n S<\/jats:italic>\n . Typhi pathogenesis and antibiotic resistance. However, our study is limited by the use of\n in vitro<\/jats:italic>\n models and does not reflect the complex interactions between\n S<\/jats:italic>\n . Typhi and host cells\n in vivo<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fmicb.2023.1301478","type":"journal-article","created":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T06:27:11Z","timestamp":1698992831000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Deletion of Salmonella enterica serovar Typhi tolC reduces bacterial adhesion and invasion toward host cells"],"prefix":"10.3389","volume":"14","author":[{"given":"Ashraf","family":"Hussain","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene Boon Beng","family":"Ong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prabha","family":"Balaram","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asma","family":"Ismail","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phua Kia","family":"Kien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,11,3]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1016\/j.resmic.2004.03.005","article-title":"Identification of a new Salmonella enterica serovar Enteritidis locus involved in cell invasion and in the colonisation of chicks","volume":"155","author":"Amy","year":"2004","journal-title":"Res. Microbiol."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1046\/j.1365-2958.1998.00976.x","article-title":"The RcsB-RcsC regulatory system of Salmonella typhi differentially modulates the expression of invasion proteins, flagellin and Vi antigen in response to osmolarity","volume":"29","author":"Arricau","year":"1998","journal-title":"Mol. Microbiol."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"2006.0008","DOI":"10.1038\/msb4100050","article-title":"Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection","volume":"2","author":"Baba","year":"2006","journal-title":"Mol. Syst. Biol."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1111\/j.1462-5822.2005.00671.x","article-title":"The AcrAB-TolC efflux system of Salmonella enterica serovar Typhimurium plays a role in pathogenesis","volume":"8","author":"Buckley","year":"2006","journal-title":"Cell. Microbiol."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"4949","DOI":"10.1128\/JB.181.16.4949-4954.1999","article-title":"InvF is required for expression of genes encoding proteins secreted by the SPI1 type III secretion apparatus in Salmonella typhimurium","volume":"181","author":"Darwin","year":"","journal-title":"J. Bacteriol."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1128\/CMR.12.3.405","article-title":"Molecular basis of the interaction of Salmonella with the intestinal mucosa","volume":"12","author":"Darwin","year":"","journal-title":"Clin. Microbiol. Rev."},{"key":"ref9001","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1073\/pnas.120163297","article-title":"One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products","volume":"97","author":"Datsenko","year":"2000","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1099\/13500872-145-5-1023","article-title":"Fimbriae- and flagella-mediated association with and invasion of cultured epithelial cells by Salmonella enteritidis","volume":"145","author":"Dibb-Fuller","year":"1999","journal-title":"Microbiology"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"163","DOI":"10.3390\/antibiotics2010163","article-title":"Resistance-nodulation-division multidrug efflux pumps in gram-negative bacteria: role in virulence","volume":"2","author":"Fernando","year":"2013","journal-title":"Antibiotics"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1146\/annurev.cellbio.17.1.53","article-title":"Salmonella interactions with host cells: type III secretion at work","volume":"17","author":"Galan","year":"2001","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref9002","first-page":"887","article-title":"Role of TolC in virulence of salmonella enterica serovar Typhi","volume":"10","author":"Hussain","year":"2016","journal-title":"J. Pure Appl. Microbiol."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1016\/S1286-4579(01)01498-8","article-title":"Introduction: microbiology and immunology: lessons learned from Salmonella","volume":"3","author":"Kaufmann","year":"2001","journal-title":"Microbes Infect."},{"key":"ref9003","doi-asserted-by":"publisher","first-page":"1861","DOI":"10.1128\/jcm.00109-08","article-title":"PCR method to identify Salmonella enterica serovars Typhi, Paratyphi A, and Paratyphi B among Salmonella Isolates from the blood of patients with clinical enteric fever","volume":"46","author":"Levy","year":"2008","journal-title":"J. Clin. Microbiol."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"159","DOI":"10.2165\/00003495-200464020-00004","article-title":"Efflux-mediated drug resistance in bacteria","volume":"64","author":"Li","year":"2004","journal-title":"Drugs"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref13","first-page":"657","article-title":"An instrument-free method for the demonstration of efflux pump activity of bacteria","volume":"20","author":"Martins","year":"2006","journal-title":"In Vivo"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1111\/j.1365-2958.2005.04940.x","article-title":"Virulence and drug resistance roles of multidrug efflux systems of Salmonella enterica serovar Typhimurium","volume":"59","author":"Nishino","year":"2006","journal-title":"Mol. Microbiol."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.micinf.2012.10.014","article-title":"Deletion of invH gene in Salmonella enterica serovar Typhimurium limits the secretion of Sip effector proteins","volume":"15","author":"Pati","year":"2013","journal-title":"Microbes Infect."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1128\/CMR.19.2.382-402.2006","article-title":"Clinically relevant chromosomally encoded multidrug resistance efflux pumps in bacteria","volume":"19","author":"Piddock","year":"","journal-title":"Clin. Microbiol. Rev."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1038\/nrmicro1464","article-title":"Multidrug-resistance efflux pumps - not just for resistance","volume":"4","author":"Piddock","year":"","journal-title":"Nat. Rev. Microbiol."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/j.micinf.2015.01.004","article-title":"How bacterial pathogens colonize their hosts and invade deeper tissues","volume":"17","author":"Ribet","year":"2015","journal-title":"Microbes Infect."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"6039","DOI":"10.1128\/AEM.71.10.6039-6048.2005","article-title":"Investigation of specific substitutions in virulence genes characterizing phenotypic groups of low-virulence field strains of Listeria monocytogenes","volume":"71","author":"Roche","year":"2005","journal-title":"Appl. Environ. Microbiol."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1186\/1471-2180-10-180","article-title":"Absence of functional TolC protein causes increased stress response gene expression in Sinorhizobium meliloti","volume":"10","author":"Santos","year":"2010","journal-title":"BMC Microbiol."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.jprot.2012.12.025","article-title":"Proteomic and phenotypic analysis of triclosan tolerant verocytotoxigenic Escherichia coli O157: H19","volume":"80","author":"Sheridan","year":"2013","journal-title":"J. Proteome"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1016\/j.bbrc.2014.05.090","article-title":"Bacterial multidrug efflux pumps: mechanisms, physiology and pharmacological exploitations","volume":"453","author":"Sun","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1271\/bbb.80778","article-title":"Biogenesis of outer membranes in gram-negative bacteria","volume":"73","author":"Tokuda","year":"2009","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1016\/j.ijmm.2007.12.006","article-title":"TolC, but not AcrB, is involved in the invasiveness of multidrug-resistant Salmonella enterica serovar typhimurium by increasing type III secretion system-1 expression","volume":"298","author":"Virlogeux-Payant","year":"2008","journal-title":"Int. J. Med. Microbiol."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"4276","DOI":"10.1128\/JB.00363-09","article-title":"The global consequence of disruption of the AcrAB-TolC efflux pump in Salmonella enterica includes reduced expression of SPI-1 and other attributes required to infect the host","volume":"191","author":"Webber","year":"2009","journal-title":"J. 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