{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T21:25:53Z","timestamp":1785187553310,"version":"3.55.0"},"reference-count":67,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,11]],"date-time":"2021-12-11T00:00:00Z","timestamp":1639180800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Salmonella enterica is a common cause of many enteric infections worldwide and is successfully engineered to deliver heterologous antigens to be used as vaccines. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) RNA-guided Cas9 endonuclease is a promising genome editing tool. In the current study, a CRISPR-Cas9 system was used to target S.enterica\u00a0sdiA that encodes signal molecule receptor SdiA and responds to the quorum sensing (QS) signaling compounds N-acylhomoserine lactones (AHLs). For this purpose, sdiA was targeted in both S.enterica wild type (WT) and the \u0394ssaV mutant strain, where SsaV has been reported to be an essential component of SPI2-T3SS. The impact of sdiA mutation on S.\u00a0enterica virulence was evaluated at both early invasion and later intracellular replication in both the presence and absence of AHL. Additionally, the influence of sdiA mutation on the pathogenesis S.\u00a0enterica WT and mutants was investigated in vivo, using mice infection model. Finally, the minimum inhibitory concentrations (MICs) of various antibiotics against S.\u00a0enterica strains were determined. Present findings show that mutation in sdiA significantly affects S.enterica biofilm formation, cell adhesion and invasion. However, sdiA mutation did not affect bacterial intracellular survival. Moreover, in vivo bacterial pathogenesis was markedly lowered in S.enterica \u0394sdiA in comparison with the wild-type strain. Significantly, double-mutant sdiA and ssaV attenuated the S. enterica virulence and in vivo pathogenesis. Moreover, mutations in selected genes increased Salmonella susceptibility to tested antibiotics, as revealed by determining the MICs and MBICs of these antibiotics. Altogether, current results clearly highlight the importance of the CRISPR-Cas9 system as a bacterial genome editing tool and the valuable role of SdiA in S.enterica virulence. The present findings extend the understanding of virulence regulation and host pathogenesis of Salmonellaenterica.<\/jats:p>","DOI":"10.3390\/microorganisms9122564","type":"journal-article","created":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T01:29:33Z","timestamp":1639358973000},"page":"2564","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["Alteration of Salmonella enterica Virulence and Host Pathogenesis through Targeting sdiA by Using the CRISPR-Cas9 System"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4282-6789","authenticated-orcid":false,"given":"Momen","family":"Askoura","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1333-980X","authenticated-orcid":false,"given":"Ahmad J.","family":"Almalki","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia"},{"name":"Center of Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7385-868X","authenticated-orcid":false,"given":"Amr S. Abu","family":"Lila","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt"},{"name":"Department of Pharmaceutics, College of Pharmacy, University of Hail, Hail 81442, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1913-9005","authenticated-orcid":false,"given":"Khaled","family":"Almansour","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, University of Hail, Hail 81442, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5055-6256","authenticated-orcid":false,"given":"Farhan","family":"Alshammari","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, University of Hail, Hail 81442, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3741-0893","authenticated-orcid":false,"given":"El-Sayed","family":"Khafagy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-kharj 11942, Saudi Arabia"},{"name":"Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Suez Canal University, Ismailia 41552, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3049-4617","authenticated-orcid":false,"given":"Tarek S.","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5683-4803","authenticated-orcid":false,"given":"Wael A. H.","family":"Hegazy","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"111","DOI":"10.2217\/fmb.11.144","article-title":"Salmonella enterica as a vaccine carrier","volume":"7","author":"Hegazy","year":"2012","journal-title":"Futur. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/nrmicro1788","article-title":"Salmonellae interplay with host cells","volume":"6","author":"Haraga","year":"2008","journal-title":"Nat. Rev. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1128\/MMBR.68.4.771-795.2004","article-title":"Process of protein transport by the Type III secretion system","volume":"68","author":"Ghosh","year":"2004","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_4","first-page":"317","article-title":"Salmonella pathogenicity islands in host specificity, host pathogen-interactions and antibiotics re-sistance of Salmonella enterica","volume":"120","author":"Gerlach","year":"2007","journal-title":"Berl. Munch. Tierarztl. Wochenschr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1093\/femspd\/ftaa011","article-title":"Ciprofloxacin interferes with Salmonella Typhimurium intracellular survival and host virulence through repression of Salmonella pathogenicity island-2 (SPI-2) genes expression","volume":"78","author":"Askoura","year":"2020","journal-title":"Pathog. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"6965","DOI":"10.1128\/IAI.00648-06","article-title":"The translocated Salmonella effector proteins SseF and SseG interact and are required to establish an intracellular replication niche","volume":"74","author":"Deiwick","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1111\/j.1574-695X.2007.00364.x","article-title":"Identification of Salmonella SPI-2 secretion system compo-nents required for SpvB-mediated cytotoxicity in macrophages and virulence in mice","volume":"52","author":"Browne","year":"2008","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"718","DOI":"10.5897\/AJB2016.15852","article-title":"Evaluation of the role of SsaV Salmonella pathogenicity island-2 dependent type III secretion system components on the virulence behavior of Salmonella enterica serovar Typhimurium","volume":"16","author":"Wael","year":"2017","journal-title":"Afr. J. Biotechnol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Abbas, H.A., and Hegazy, W.A.H. (2020). Repurposing anti-diabetic drug \u201cSitagliptin\u201d as a novel virulence attenuating agent in Serratia marcescens. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0231625"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Hegazy, W.A.H., Khayat, M.T., Ibrahim, T.S., Nassar, M.S., Bakhrebah, M.A., Abdulaal, W.H., Alhakamy, N.A., and Bendary, M.M. (2020). Repurposing anti-diabetic drugs to cripple Quorum sensing in Pseudomonas aeruginosa. Microorganisms, 8.","DOI":"10.3390\/microorganisms8091285"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"103777","DOI":"10.1016\/j.micpath.2019.103777","article-title":"Investigating the influence of iron on Campylobacter jejuni transcriptome in re-sponse to acid stress","volume":"138","author":"Askoura","year":"2020","journal-title":"Microb. Pathog."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"6204","DOI":"10.1128\/AEM.01458-14","article-title":"Punicalagin inhibits Salmonella virulence factors and has anti-quorum-sensing potential","volume":"80","author":"Li","year":"2014","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1517\/13543776.2013.779674","article-title":"Quorum sensing inhibitors: A patent review","volume":"23","author":"Jiang","year":"2013","journal-title":"Expert Opin. Ther. Patents"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Khayyat, A., Hegazy, W., Shaldam, M., Mosbah, R., Almalki, A., Ibrahim, T., Khayat, M., Khafagy, E.-S., Soliman, W., and Abbas, H. (2021). Xylitol inhibits growth and blocks virulence in Serratia marcescens. Microorganism, 9.","DOI":"10.3390\/microorganisms9051083"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1128\/AEM.01451-06","article-title":"Synthesis of N-Acyl Homoserine Lactone analogues reveals strong activators of SdiA, the Salmonella en-terica Serovar Typhimurium LuxR Homologue","volume":"73","author":"Janssens","year":"2007","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5733","DOI":"10.1128\/JB.183.19.5733-5742.2001","article-title":"SdiA of Salmonella enterica is a LuxR Homolog that detects mixed microbial communities","volume":"183","author":"Michael","year":"2001","journal-title":"J. Bacteriol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1128\/JB.185.4.1357-1366.2003","article-title":"Detection of other microbial species by Salmonella: Expression of the SdiA regulon","volume":"185","author":"Smith","year":"2003","journal-title":"J. Bacteriol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1128\/IAI.06056-11","article-title":"Evaluation of Salmonella enterica Type III secretion system effector proteins as carriers for heterologous vaccine antigens","volume":"80","author":"Hegazy","year":"2012","journal-title":"Infect. Immun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"6260","DOI":"10.1158\/0008-5472.CAN-14-1169","article-title":"Effective cancer vaccine platform based on attenuated Salmonella and a Type III secretion system","volume":"74","author":"Xu","year":"2014","journal-title":"Cancer Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"207","DOI":"10.2174\/1566523034578357","article-title":"Tumor-specific gene delivery using genetically engineered bacteria","volume":"3","author":"Theys","year":"2003","journal-title":"Curr. Gene Ther."},{"key":"ref_21","first-page":"331","article-title":"RNA-guided genetic silencing systems in bacteria and archaea","volume":"482","author":"Wiedenheft","year":"2012","journal-title":"Nat. Cell Biol."},{"key":"ref_22","first-page":"50","article-title":"Rewriting a genome","volume":"495","author":"Charpentier","year":"2013","journal-title":"Nat. Cell Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1146\/annurev.micro.112408.134123","article-title":"CRISPR\/Cas system and its role in phage-bacteria interactions","volume":"64","author":"Deveau","year":"2010","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1126\/science.1179555","article-title":"CRISPR\/Cas, the immune system of bacteria and Archaea","volume":"327","author":"Horvath","year":"2010","journal-title":"Science"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/nbt.2508","article-title":"RNA-guided editing of bacterial genomes using CRISPR-Cas sys-tems","volume":"31","author":"Jiang","year":"2013","journal-title":"Nat. Biotechnol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2506","DOI":"10.1128\/AEM.04023-14","article-title":"Multigene editing in the Escherichia coli genome via the CRISPR-Cas9 system","volume":"81","author":"Jiang","year":"2015","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e131","DOI":"10.1093\/nar\/gku623","article-title":"CRISPR\u2013Cas9-assisted recombineering in Lactobacillus reuteri","volume":"42","author":"Oh","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jbiotec.2015.02.005","article-title":"Markerless chromosomal gene deletion in Clostrid-ium beijerinckii using CRISPR\/Cas9 system","volume":"200","author":"Wang","year":"2015","journal-title":"J. Biotechnol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1111\/pbi.12465","article-title":"Designed nucleases for targeted genome editing","volume":"14","author":"Lee","year":"2015","journal-title":"Plant. Biotechnol. J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1975","DOI":"10.1093\/mp\/sst119","article-title":"RNA-guided genome editing in plants using a CRISPR\u2013Cas system","volume":"6","author":"Xie","year":"2013","journal-title":"Mol. Plant."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1016\/j.cell.2014.05.010","article-title":"Development and applications of CRISPR-Cas9 for genome engineering","volume":"157","author":"Hsu","year":"2014","journal-title":"Cell"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Braukmann, M., Methner, U., and Berndt, A. (2015). Immune reaction and survivability of Salmonella Typhimurium and Salmonella Infantis after infection of primary avian macrophages. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0122540"},{"key":"ref_33","first-page":"3329","article-title":"TALENs construction: Slowly but surely","volume":"17","author":"Hegazy","year":"2016","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2551","DOI":"10.1099\/mic.0.28048-0","article-title":"Clustered regularly interspaced short palindrome repeats (CRISPRs) have spacers of extrachromosomal origin","volume":"151","author":"Bolotin","year":"2005","journal-title":"Microbiology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1007\/s00239-004-0046-3","article-title":"Intervening sequences of regularly spaced prokaryotic repeats derive from foreign genetic elements","volume":"60","author":"Mojica","year":"2005","journal-title":"J. Mol. Evol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1099\/mic.0.27437-0","article-title":"CRISPR elements in Yersinia pestis acquire new repeats by preferential uptake of bac-teriophage DNA, and provide additional tools for evolutionary studies","volume":"151","author":"Pourcel","year":"2005","journal-title":"Microbiology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1126\/science.1165771","article-title":"CRISPR interference limits horizontal gene transfer in Staphylococci by targeting DNA","volume":"322","author":"Marraffini","year":"2008","journal-title":"Sci-ence"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/mmi.12640","article-title":"Adapting to new threats: The generation of memory by CRISPR-Cas immune systems","volume":"93","author":"Heler","year":"2014","journal-title":"Mol. Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/nrmicro2577","article-title":"Evolution and classification of the CRISPR\u2013Cas systems","volume":"9","author":"Makarova","year":"2011","journal-title":"Nat. Rev. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"249","DOI":"10.4161\/fly.26566","article-title":"CRISPR\/Cas9-mediated genome engineering and the promise of designer flies on demand","volume":"7","author":"Gratz","year":"2013","journal-title":"Fly"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1146\/annurev-micro-091014-104441","article-title":"CRISPR-Cas: New tools for genetic manipulations from bacterial immunity systems","volume":"69","author":"Jiang","year":"2015","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1093\/abbs\/gmv007","article-title":"One-step high-efficiency CRISPR\/Cas9-mediated genome editing in Strepto-myces","volume":"47","author":"Huang","year":"2015","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3360","DOI":"10.1128\/IAI.00404-12","article-title":"Diarrhea and Colitis in mice require the Salmonella Pathogenicity Island 2-Encoded secretion function but Not SifA or Spv effectors","volume":"80","author":"Fierer","year":"2012","journal-title":"Infect. Immun."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1080\/03079450902737771","article-title":"Functions exerted by the virulence-associated type-three secretion systems during Salmonella enterica serovar Enteritidis invasion into and survival within chicken oviduct epithelial cells and macro-phages","volume":"38","author":"Li","year":"2009","journal-title":"Avian Pathol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.mimet.2004.09.013","article-title":"Measurement of bacterial adhesion\u2014In vitro evaluation of different meth-ods","volume":"60","author":"Vesterlund","year":"2005","journal-title":"J. Microbiol. Methods"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"89","DOI":"10.33073\/pjm-2010-013","article-title":"Evaluation of quantitative PCR Measurement of bacterial colonization of Epithelial cells","volume":"59","author":"Schmidt","year":"2010","journal-title":"Pol. J. Microbiol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Khayyat, A., Abbas, H., Mohamed, M., Asfour, H., Khayat, M., Ibrahim, T., Youns, M., Khafagy, E.-S., Abu Lila, A., and Safo, M. (2021). Not only antimicrobial: Metronidazole Mitigates the virulence of Proteus mirabilis isolated from macerated diabetic foot ulcer. Appl. Sci., 11.","DOI":"10.3390\/app11156847"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/S0167-7012(00)00122-6","article-title":"A modified microtiter-plate test for quantification of staphylococcal biofilm formation","volume":"40","year":"2000","journal-title":"J. Microbiol. Methods"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Al Saqr, A., Aldawsari, M.F., Khafagy, E.-S., Shaldam, M.A., Hegazy, W.A.H., and Abbas, H.A. (2021). A novel use of Allopurinol as a quorum-sensing inhibitor in Pseudomonas aeruginosa. Antibiotics, 10.","DOI":"10.3390\/antibiotics10111385"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"H\u00f6lzer, S.U., and Hensel, M. (2012). Divergent roles of Salmonella Pathogenicity Island 2 and metabolic traits during interaction of S. en-terica Serovar Typhimurium with host cells. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0033220"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Aldawsari, M., Khafagy, E.-S., Saqr, A., Alalaiwe, A., Abbas, H., Shaldam, M., Hegazy, W., and Goda, R. (2021). Tackling virulence of Pseudomonas aeruginosa by the Natural Furanone Sotolon. Antibiotics, 10.","DOI":"10.3390\/antibiotics10070871"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Al Saqr, A., Khafagy, E.-S., Alalaiwe, A., Aldawsari, M., Alshahrani, S., Anwer, K., Khan, S., Lila, A., Arab, H., and Hegazy, W. (2021). Synthesis of gold nanoparticles by using green machinery: Characterization and in vitro toxicity. Nanomaterials, 11.","DOI":"10.3390\/nano11030808"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Khayyat, A.N., Abbas, H.A., Khayat, M.T., Shaldam, M.A., Askoura, M., Asfour, H.Z., Khafagy, E.-S., Abu Lila, A.S., Allam, A.N., and Hegazy, W.A.H. (2021). Secnidazole is a promising imidazole mitigator of Serratia marcescens virulence. Microorganism, 9.","DOI":"10.3390\/microorganisms9112333"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1007\/s42770-021-00465-8","article-title":"Repurposing of antidiabetics as Serratia marcescens virulence inhibitors","volume":"52","author":"Hegazy","year":"2021","journal-title":"Braz. J. Microbiol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Bendary, M.M., Ibrahim, D., Mosbah, R.A., Mosallam, F., Hegazy, W.A.H., Awad, N.F.S., Alshareef, W.A., Al Omar, S.Y., Zaitone, S.A., and El-Hamid, M.I.A. (2020). Thymol Nanoemulsion: A new therapeutic option for extensively drug resistant foodborne pathogens. Antibiotics, 10.","DOI":"10.3390\/antibiotics10010025"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1016\/j.femsre.2005.03.005","article-title":"Salmonella stress management and its relevance to behaviour during intestinal colonisation and infec-tion","volume":"29","author":"Rychlik","year":"2005","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.mib.2011.01.006","article-title":"Detection of acyl-homoserine lactones by Escherichia and Salmonella","volume":"14","author":"Soares","year":"2011","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Smith, J.N., Dyszel, J.L., Soares, J.A., Ellermeier, C.D., Altier, C., Lawhon, S.D., Adams, L.G., Konjufca, V., Curtiss, R., and Slauch, J.M. (2008). SdiA, an N-Acylhomoserine lactone receptor, becomes active during the transit of Salmonella enterica through the gastrointestinal tract of turtles. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0002826"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Liu, Z., Que, F., Liao, L., Zhou, M., You, L., Zhao, Q., Li, Y., Niu, H., Wu, S., and Huang, R. (2014). Study on the promotion of bacterial biofilm formation by a Salmonella Conjugative Plasmid and the Underlying mechanism. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0109808"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/nrg2749","article-title":"CRISPR interference: RNA-directed adaptive immunity in bacteria and archaea","volume":"11","author":"Marraffini","year":"2010","journal-title":"Nat. Rev. Genet."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/1751-0147-53-44","article-title":"Salmonella Typhimurium invasion of HEp-2 epithelial cells in vitro is increased by N-acylhomoserine lactone quorum sensing signals","volume":"53","author":"Nesse","year":"2011","journal-title":"Acta Vet. Scand."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1128\/JB.185.3.991-1000.2003","article-title":"Characterization of SrgA, a Salmonella en-terica Serovar Typhimurium virulence plasmid-encoded paralogue of the Disulfide Oxidoreductase DsbA, essential for bio-genesis of plasmid-encoded fimbriae","volume":"185","author":"Bouwman","year":"2003","journal-title":"J. Bacteriol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"34631","DOI":"10.1074\/jbc.M402760200","article-title":"Two periplasmic disulfide oxidoreductases, DsbA and SrgA, target outer membrane protein SpiA, a component of the Salmonella Pathogenicity Island 2 Type III secretion system","volume":"279","author":"Miki","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Pati, N.B., Vishwakarma, V., Selvaraj, S.K., Dash, S., Saha, B., Singh, N., and Suar, M. (2013). Salmonella Typhimurium TTSS-2 deficient mig-14 mutant shows attenuation in immunocompromised mice and offers protection against wild-type Salmonella Typhi-murium infection. BMC Microbiol., 13.","DOI":"10.1186\/1471-2180-13-236"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1637\/8642-020309-Reg.1","article-title":"Induction of CXC Chemokine messenger-RNA expression in chicken oviduct epithelial cells by Salmonella enterica serovar Enteritidis via the type three secretion system\u20131","volume":"53","author":"Li","year":"2009","journal-title":"Avian Dis."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Periaswamy, B., Maier, L., Vishwakarma, V., Slack, E., Kremer, M., Andrews-Polymenis, H.L., McClelland, M., Grant, A.J., Suar, M., and Hardt, W.-D. (2012). Live attenuated S. Typhimurium vaccine with improved safety in immuno-compromised mice. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0045433"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Aldawsari, M., Alalaiwe, A., Khafagy, E.-S., Al Saqr, A., Alshahrani, S., Alsulays, B., Alshehri, S., Abu Lila, A., Rizvi, S.D., and Hegazy, W. (2021). Efficacy of SPG-ODN 1826 Nanovehicles in inducing M1 phenotype through TLR-9 activation in murine alveolar J774A.1 cells: Plausible nano-immunotherapy for lung carcinoma. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22136833"}],"updated-by":[{"DOI":"10.3390\/microorganisms14010245","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2021,12,11]],"date-time":"2021-12-11T00:00:00Z","timestamp":1639180800000}}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/9\/12\/2564\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T11:11:33Z","timestamp":1768993893000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/9\/12\/2564"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,11]]},"references-count":67,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["microorganisms9122564"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms9122564","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,11]]}}}