{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:28:00Z","timestamp":1791822480979,"version":"4.3.4"},"reference-count":136,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,10,11]],"date-time":"2022-10-11T00:00:00Z","timestamp":1665446400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Salmonella enterica serovar Typhi (S. Typhi) is a Gram-negative pathogen that causes typhoid fever in humans. Though many serotypes of Salmonella spp. are capable of causing disease in both humans and animals alike, S. Typhi and S. Paratyphi are common in human hosts only. The global burden of typhoid fever is attributable to more than 27 million cases each year and approximately 200,000 deaths worldwide, with many regions such as Africa, South and Southeast Asia being the most affected in the world. The pathogen is able to cause disease in hosts by evading defense systems, adhesion to epithelial cells, and survival in host cells in the presence of several virulence factors, mediated by virulence plasmids and genes clustered in distinct regions known as Salmonella pathogenicity islands (SPIs). These factors, coupled with plasmid-mediated antimicrobial resistance genes, enable the bacterium to become resistant to various broad-spectrum antibiotics used in the treatment of typhoid fever and other infections caused by Salmonella spp. The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains in many countries of the world has raised great concern over the rise of antibiotic resistance in pathogens such as S. Typhi. In order to identify the key virulence factors involved in S. Typhi pathogenesis and infection, this review delves into various mechanisms of virulence, pathogenicity, and antimicrobial resistance to reinforce efficacious disease management.<\/jats:p>","DOI":"10.3390\/microorganisms10102006","type":"journal-article","created":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T02:10:27Z","timestamp":1665540627000},"page":"2006","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Understanding the Mechanism of Antimicrobial Resistance and Pathogenesis of Salmonella enterica Serovar Typhi"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8011-7951","authenticated-orcid":false,"given":"Maryam","family":"Khan","sequence":"first","affiliation":[{"name":"Institute of Molecular Biology and Biotechnology, The University of Lahore, Defence Road Campus, Lahore 54000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saba","family":"Shamim","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Biotechnology, The University of Lahore, Defence Road Campus, Lahore 54000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,11]]},"reference":[{"key":"ref_1","first-page":"925","article-title":"Polyosides (encapsulated bacteria)","volume":"322","author":"Lindberg","year":"1999","journal-title":"Comptes Rendus Acad. Sci. III"},{"key":"ref_2","first-page":"e000425","article-title":"Comparing serotyping with whole-genome sequencing for subtyping of non-typhoidal Salmonella enterica: A large-scale analysis of 37 serotypes with a public health impact in the USA","volume":"6","author":"Elnekave","year":"2020","journal-title":"Microb. Genom."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"104352","DOI":"10.1016\/j.micpath.2020.104352","article-title":"A review on the origin of multidrug-resistant Salmonella and perspective of tailored phoP gene towards avirulence","volume":"147","author":"Gangathraprabhu","year":"2020","journal-title":"Microb. Pathog."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1093\/cid\/ciy846","article-title":"Progress in typhoid fever epidemiology","volume":"68","author":"Crump","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1017\/S0950268897008558","article-title":"Risk factors for typhoid fever in an endemic setting, Karachi, Pakistan","volume":"120","author":"Luby","year":"1998","journal-title":"Epidemiol. Infect."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2655801","DOI":"10.1155\/2022\/2655801","article-title":"Mechanisms for the invasion and dissemination of Salmonella","volume":"2022","author":"Li","year":"2022","journal-title":"Can. J. Infect. Dis. Med. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.1093\/cid\/ciab745","article-title":"Spatial and genomic data to characterize endemic typhoid transmission","volume":"74","author":"Gauld","year":"2022","journal-title":"Clin. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"E122","DOI":"10.1017\/S0950268822000759","article-title":"Rainfall anomalies and typhoid fever in Blantyre, Malawi","volume":"150","author":"Gauld","year":"2022","journal-title":"Epidemiol. Infect."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e00167-19","DOI":"10.1128\/JCM.00167-19","article-title":"Real-time PCR assay for differentiation of typhoidal and nontyphoidal Salmonella","volume":"57","author":"Nair","year":"2019","journal-title":"J. Clin. Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1086\/314766","article-title":"A massive epidemic of multidrug-resistant typhoid fever in Tajikistan associated with consumption of municipal water","volume":"179","author":"Mermin","year":"1999","journal-title":"J. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Karkey, A., Thompson, C.N., Tran Vu Thieu, N., Dongol, S., Le Thi Phuong, T., Voong Vinh, P., Arjyal, A., Martin, L.B., Rondini, S., and Farrar, J.J. (2013). Differential epidemiology of Salmonella Typhi and Paratyphi A in Kathmandu, Nepal: A matched case control investigation in a highly endemic enteric fever setting. PLoS Negl. Trop. Dis., 7.","DOI":"10.1371\/journal.pntd.0002391"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1056\/NEJMra020201","article-title":"Typhoid fever","volume":"347","author":"Parry","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/S1473-3099(05)70239-5","article-title":"Typhoid and paratyphoid fever in travellers","volume":"5","author":"Connor","year":"2005","journal-title":"Lancet Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"101946","DOI":"10.1016\/j.tmaid.2020.101946","article-title":"Typhoid fever infection\u2014Antibiotic resistance and vaccination strategies: A narrative review","volume":"40","author":"Atouguia","year":"2021","journal-title":"Travel Med. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1086\/649541","article-title":"Global trends in typhoid and paratyphoid Fever","volume":"50","author":"Crump","year":"2010","journal-title":"Clin. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1016\/S0140-6736(13)62708-7","article-title":"Typhoid fever","volume":"385","author":"Wain","year":"2015","journal-title":"Lancet"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","article-title":"Global, regional, and national sepsis incidence and mortality, 1990\u20132017: Analysis for the Global Burden of Disease Study","volume":"395","author":"Rudd","year":"2020","journal-title":"Lancet"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Mukherjee, N., Nolan, V.G., Dunn, J.R., and Banerjee, P. (2019). Sources of human infection by Salmonella enterica serotype Javiana: A systematic review. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0222108"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1111\/age.12341","article-title":"Splenic gene expression profiling in white leghorn layer inoculated with the Salmonella enterica serovar enteritidis","volume":"46","author":"Wu","year":"2015","journal-title":"Anim. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"EFSA, and ECDC (2021). The European Union One Health 2020 Zoonoses Report. EFSA J., 19, e6971\u2013e7295.","DOI":"10.2903\/j.efsa.2021.6971"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s41043-018-0144-2","article-title":"Investigation of a Typhoid fever epidemic in Moyale Sub-County, Keny-2015","volume":"37","author":"Galgallo","year":"2018","journal-title":"J. Health Popul. Nutr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2667","DOI":"10.3389\/fmicb.2019.02667","article-title":"Multistate outbreaks of foodborne illness in the united states associated with fresh produce from 2010 to 2017","volume":"10","author":"Carstens","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"805384","DOI":"10.3389\/fcimb.2022.805384","article-title":"Prevalence, serotype distribution and antimicrobial resistance of non-typhoidal Salmonella in hospitalized patients in Conghua District of Guangzhou, China","volume":"12","author":"Gong","year":"2022","journal-title":"Front. Cell Infect. Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"S117","DOI":"10.1093\/cid\/ciy1124","article-title":"Epidemiology of typhoid and paratyphoid: Implications for vaccine policy","volume":"68","author":"Saha","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/S0140-6736(05)67181-4","article-title":"Typhoid and paratyphoid fever","volume":"366","author":"Bhan","year":"2005","journal-title":"Lancet"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Lozano-Le\u00f3n, A., Garc\u00eda-Omil, C., Rodr\u00edguez-Souto, R.R., Lamas, A., and Garrido-Maestu, A. (2022). An evaluation of the pathogenic potential, and the antimicrobial resistance, of Salmonella strains isolated from mussels. Microorganisms, 10.","DOI":"10.3390\/microorganisms10010126"},{"key":"ref_27","first-page":"346","article-title":"The global burden of typhoid fever","volume":"82","author":"Crump","year":"2004","journal-title":"Bull. World Health Organ."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1146\/annurev-micro-091313-103739","article-title":"Salmonella enterica serovar Typhi and the pathogenesis of typhoid fever","volume":"68","author":"Dougan","year":"2014","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e1062","DOI":"10.1016\/S2214-109X(18)30312-7","article-title":"Typhoid fever outbreak with severe complications in Yucatan, Mexico","volume":"6","author":"Campos","year":"2018","journal-title":"Lancet Glob. Health"},{"key":"ref_30","unstructured":"IHME (2022, July 01). Global Burden of Disease Collaborative Network. GBD 2020 Cause and Risk Summaries: Typhoid Fever\u2014Level 4 Cause. Seattle, United States: Institute for Health Metrics and Evaluation (IHME). Available online: http:\/\/www.healthdata.org\/results\/gbd_summaries\/2019\/typhoid-fever-level-4-cause."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4","DOI":"10.4269\/ajtmh.18-0032","article-title":"Introductory article on global burden and epidemiology of typhoid fever","volume":"99","author":"Radhakrishnan","year":"2018","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_32","first-page":"e22316","article-title":"A rare case of typhoid fever in the United States associated with travel to Mexico","volume":"14","author":"Kim","year":"2022","journal-title":"Cureus"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.ijid.2022.03.036","article-title":"Toward typhoid fever elimination","volume":"119","author":"Khanam","year":"2022","journal-title":"Int. J. Infect. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/S1473-3099(19)30051-9","article-title":"Extensively drug-resistant typhoid fever in Pakistan","volume":"19","author":"Rasheed","year":"2019","journal-title":"Lancet Infect. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6432580","DOI":"10.1155\/2020\/6432580","article-title":"Extensively drug-resistant (XDR) typhoid: Evolution, prevention, and its management","volume":"2020","author":"Akram","year":"2020","journal-title":"BioMed Res. Int."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"S243","DOI":"10.1093\/infdis\/jix122","article-title":"Social and economic burden associated with typhoid fever in Kathmandu and surrounding areas: A qualitative study","volume":"218","author":"Kaljee","year":"2018","journal-title":"J. Infect. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.3201\/eid1611.100388","article-title":"Typhoid fever among children","volume":"16","author":"Marks","year":"2010","journal-title":"Ghana Emerg. Infect. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Karkey, A., Arjyal, A., Anders, K.L., Boni, M.F., Dongol, S., Koirala, S., My, P.V., Nga, T.V., Clements, A.C., and Holt, K.E. (2010). The burden and characteristics of enteric fever at a healthcare facility in a densely populated area of Kathmandu. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0013988"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e570","DOI":"10.1016\/S2214-109X(14)70301-8","article-title":"Burden of typhoid fever in low income and middle-income countries: A systematic, literature-based update with risk-factor adjustment","volume":"2","author":"Mogasale","year":"2014","journal-title":"Lancet Glob. Health"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1093\/cid\/cix042","article-title":"Evaluation of the clinical and microbiological response to Salmonella paratyphi a infection in the first paratyphoid human challenge model","volume":"64","author":"Dobinson","year":"2017","journal-title":"Clin. Infect. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1093\/cid\/cis025","article-title":"A large outbreak of typhoid fever associated with a high rate of intestinal perforation in Kasese District, Uganda, 2008\u20132009","volume":"54","author":"Neil","year":"2012","journal-title":"Clin. Infect. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1086\/421555","article-title":"A clinical, microbiological, and pathological study of intestinal perforation associated with typhoid fever","volume":"39","author":"Nguyen","year":"2004","journal-title":"Clin. Infect. Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"704","DOI":"10.3855\/jidc.1967","article-title":"Epidemiology, clinical presentation, and patterns of drug resistance of Salmonella Typhi in Karachi, Pakistan","volume":"6","author":"Khan","year":"2012","journal-title":"J. Infect. Dev. Ctries."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1093\/cid\/cis012","article-title":"Multidrug-resistant typhoid fever with neurologic findings on the Malawi-Mozambique border","volume":"54","author":"Lutterloh","year":"2012","journal-title":"Clin. Infect. Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"875","DOI":"10.4269\/ajtmh.14-0709","article-title":"Undifferentiated febrile illness in Kathmandu, Nepal","volume":"92","author":"Thompson","year":"2015","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s12941-016-0147-z","article-title":"What proportion of Salmonella Typhi cases are detected by blood culture? A systematic literature review","volume":"15","author":"Mogasale","year":"2016","journal-title":"Ann. Clin. Microbiol. Antimicrob."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"C8","DOI":"10.1016\/j.vaccine.2015.02.030","article-title":"Diagnostics for invasive Salmonella infections: Current challenges and future directions","volume":"33","author":"Andrews","year":"2015","journal-title":"Vaccine"},{"key":"ref_48","first-page":"1","article-title":"Rapid diagnostic tests for typhoid and paratyphoid (Enteric) fever","volume":"5","author":"Wijedoru","year":"2017","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Khanam, F., Sheikh, A., Sayeed, M.A., Bhuiyan, M.S., Choudhury, F.K., Salma, U., Pervin, S., Sultana, T., Ahmed, D., and Goswami, D. (2013). Evaluation of a typhoid\/paratyphoid diagnostic assay (TPTest) detecting anti-Salmonella IgA in secretions of peripheral blood lymphocytes in patients in Dhaka, Bangladesh. PLoS Negl Trop. Dis., 7.","DOI":"10.1371\/journal.pntd.0002316"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Islam, K., Sayeed, M.A., Hossen, E., Khanam, F., Charles, R.C., Andrews, J., Ryan, E.T., and Qadri, F. (2016). Comparison of the performance of the TPTest, Tubex, Typhidot and Widal immunodiagnostic assays and blood cultures in detecting patients with typhoid fever in Bangladesh, including using a bayesian latent class modeling approach. PLoS Negl. Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0004558"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.3389\/fmicb.2017.02031","article-title":"Assessment and translation of the antibody-in-lymphocyte supernatant (als) assay to improve the diagnosis of enteric fever in two controlled human infection models and an endemic area of Nepal","volume":"8","author":"Darton","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/1476-0711-9-14","article-title":"A fast and highly sensitive blood culture PCR method for clinical detection of Salmonella enterica serovar Typhi","volume":"9","author":"Zhou","year":"2010","journal-title":"Ann. Clin. Microbiol. Antimicrob."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"S770","DOI":"10.1093\/infdis\/jiab393","article-title":"Prospects of future typhoid and paratyphoid vaccines in endemic countries","volume":"224","author":"Shakya","year":"2021","journal-title":"J. Infect. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Kuhns, M., Zautner, A.E., Rabsch, W., Zimmermann, O., Weig, M., Bader, O., and Gro\u00df, U. (2012). Rapid discrimination of Salmonella enterica serovar typhi from other serovars by MALDI-TOF mass spectrometry. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0040004"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1038\/srep01043","article-title":"Immune profiling with a Salmonella Typhi antigen microarray identifies new diagnostic biomarkers of human typhoid","volume":"3","author":"Liang","year":"2013","journal-title":"Sci. Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e03100","DOI":"10.7554\/eLife.03100","article-title":"Salmonella Typhi and Salmonella Paratyphi A elaborate distinct systemic metabolite signatures during enteric fever","volume":"3","author":"Thieu","year":"2014","journal-title":"Elife"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e15651","DOI":"10.7554\/eLife.15651","article-title":"Reproducible diagnostic metabolites in plasma from typhoid fever patients in Asia and Africa","volume":"6","author":"Parry","year":"2017","journal-title":"Elife"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"N\u00e4sstr\u00f6m, E., Jonsson, P., Johansson, A., Dongol, S., Karkey, A., Basnyat, B., Tran Vu Thieu, N., Trinh Van, T., Thwaites, G.E., and Antti, H. (2018). Diagnostic metabolite biomarkers of chronic typhoid carriage. PLoS Negl. Trop. Dis., 12.","DOI":"10.1371\/journal.pntd.0006215"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"22433","DOI":"10.1073\/pnas.0912386106","article-title":"Transcriptional response in the peripheral blood of patients infected with Salmonella enterica serovar Typhi","volume":"106","author":"Thompson","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1084\/jem.20151025","article-title":"Interferon-driven alterations of the host\u2019s amino acid metabolism in the pathogenesis of typhoid fever","volume":"213","author":"Blohmke","year":"2016","journal-title":"J. Exp. Med."},{"key":"ref_61","first-page":"e000195","article-title":"Fluoroquinolone resistance in Salmonella: Insights by whole-genome sequencing","volume":"4","author":"Cuypers","year":"2018","journal-title":"Microb Genom."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"260","DOI":"10.2471\/BLT.06.039818","article-title":"A study of typhoid fever in five Asian countries: Disease burden and implications for controls","volume":"86","author":"Ochiai","year":"2008","journal-title":"Bull. World Health Organ."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4089","DOI":"10.1074\/jbc.M412741200","article-title":"Signal-dependent binding of the response regulators PhoP and PmrA to their target promoters in vivo","volume":"280","author":"Shin","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1128\/CMR.00002-15","article-title":"Epidemiology, clinical presentation, laboratory diagnosis, antimicrobial resistance, and antimicrobial management of invasive Salmonella infections","volume":"28","author":"Crump","year":"2015","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1001\/jama.2009.1229","article-title":"Typhoid fever in the United States, 1999\u20132006","volume":"302","author":"Lynch","year":"2009","journal-title":"J. Am. Med. Assoc."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"393","DOI":"10.3855\/jidc.503","article-title":"Trends in Salmonella enterica serovar typhi in Nairobi, Kenya from 2004 to 2006","volume":"813","author":"Mengo","year":"2010","journal-title":"J. Infect. Dev. Ctries."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1016\/S1473-3099(18)30483-3","article-title":"Outbreak investigation of ceftriaxone resistant Salmonella enterica serotype Typhi and its risk factors among the general population in Hyderabad, Pakistan: A matched case-control study","volume":"18","author":"Qamar","year":"2018","journal-title":"Lancet Infect. Dis."},{"key":"ref_68","unstructured":"World Health Organization (2019). Drug resistant Salmonella infections in Pakistan: Update. Wkly. Epidemiol Monit., 12, 34."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e00492","DOI":"10.1016\/j.idcr.2019.e00492","article-title":"The first Canadian pediatric case of extensively drug-resistant Salmonella Typhi originating from an outbreak in Pakistan and its implication for empiric antimicrobial choices","volume":"15","author":"Wong","year":"2019","journal-title":"IDCases"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"286","DOI":"10.5694\/mja2.50316","article-title":"First reported case of extensively drug-resistant typhoid in Australia","volume":"211","author":"Kesson","year":"2019","journal-title":"Med. J. Aust."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1900289","DOI":"10.2807\/1560-7917.ES.2019.24.21.1900289","article-title":"Ceftriaxone resistant Salmonella enterica serotype Typhi in a pregnant traveller returning from Karachi, Pakistan to Denmark","volume":"24","author":"Engsbro","year":"2019","journal-title":"Euro Surveill."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"11","DOI":"10.15585\/mmwr.mm6801a3","article-title":"Emergence of extensively drug-resistant Salmonella Typhi infections among travelers to or from Pakistan\u2014United States, 2016\u20132018","volume":"68","author":"Medalla","year":"2019","journal-title":"Morb. Mortal. Wkly. Rep."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"S165","DOI":"10.1093\/cid\/ciy1111","article-title":"Antibiotic resistance and typhoid","volume":"68","author":"Dyson","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Bokhary, H., Pangesti, K.N.A., Rashid, H., Abd-El-Ghany, M., and Hill-Cawthorne, G.A. (2021). Travel-related antimicrobial resistance: A systematic review. Trop. Med. Infect. Dis., 6.","DOI":"10.3390\/tropicalmed6010011"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1002\/jmv.26293","article-title":"COVID-19 and Salmonella Typhi co-epidemics in Pakistan: A real problem","volume":"93","author":"Haqqi","year":"2020","journal-title":"J. Med. Virol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.1093\/cid\/ciz1112","article-title":"Phylogenetic analysis indicates a longer term presence of the globally distributed H58 haplotype of Salmonella Typhi in Southern India","volume":"71","author":"Pragasam","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"5094","DOI":"10.1038\/s41467-018-07370-z","article-title":"The phylogeography and incidence of multi-drug resistant typhoid fever in sub-Saharan Africa","volume":"9","author":"Park","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Shin, E., Park, J., Jeong, H.J., Park, A.K., Na, K., Lee, H., Chun, J.H., Hwang, K.J., Kim, C.J., and Kim, J. (2021). Emerging high-level ciprofloxacin-resistant Salmonella enterica serovar typhi haplotype H58 in travelers returning to the Republic of Korea from India. PLOS Negl. Trop. Dis., 15.","DOI":"10.1371\/journal.pntd.0009170"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Britto, C.D., Wong, V.K., Dougan, G., and Pollard, A.J. (2018). A systematic review of antimicrobial resistance in Salmonella enterica serovar Typhi, the etiological agent of typhoid. PLoS Negl. Trop. Dis., 12.","DOI":"10.1371\/journal.pntd.0006779"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"169","DOI":"10.3855\/jidc.12049","article-title":"Extended-spectrum beta-lactamases producing extensively drug-resistant Salmonella Typhi in Punjab, Pakistan","volume":"14","author":"Saeed","year":"2020","journal-title":"J. Infect. Dev. Ctries."},{"key":"ref_81","first-page":"7","article-title":"Antimicrobial resistance trends of typhoidal Salmonellae in southern Pakistan","volume":"44","author":"Shaikh","year":"2019","journal-title":"RMJ"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"788","DOI":"10.3855\/jidc.3030","article-title":"Antimicrobial resistance among blood culture isolates of Salmonella enterica in New Delhi","volume":"7","author":"Jain","year":"2013","journal-title":"J. Infect. Dev. Ctries."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"S91","DOI":"10.1093\/cid\/ciaa366","article-title":"Antimicrobial resistance in typhoidal Salmonella: Around the World in 3 Days","volume":"71","author":"Saha","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_84","first-page":"e4379","article-title":"Antimicrobial susceptibility patterns of Salmonella species in southern Pakistan","volume":"11","author":"Laghari","year":"2019","journal-title":"Cureus"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2518","DOI":"10.4269\/ajtmh.20-0258","article-title":"A systematic review on antimicrobial resistance among Salmonella Typhi worldwide","volume":"103","author":"Marchello","year":"2020","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1017\/S146625230800159X","article-title":"Antimicrobial resistance: Its emergence and transmission","volume":"9","author":"Boerlin","year":"2008","journal-title":"Anim. Health Res. Rev."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1093\/jac\/dki074","article-title":"Increase in ampC promoter strength due to mutations and deletion of the attenuator in a clinical isolate of cefoxitin-resistant Escherichia coli as determined by RT-PCR","volume":"55","author":"Tracz","year":"2005","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.ijmm.2013.02.001","article-title":"Plasmids and the spread of resistance","volume":"303","author":"Carattoli","year":"2013","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_89","first-page":"66","article-title":"Stabilization of the virulence plasmid pSLT of Salmonella Typhimurium by three maintenance systems and its evaluation by using a new stability test","volume":"3","year":"2016","journal-title":"Front. Mol. Biosci."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"129","DOI":"10.3389\/fmicb.2011.00129","article-title":"The role of the spv genes in Salmonella pathogenesis","volume":"2","author":"Guiney","year":"2011","journal-title":"Front. Microbiol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1128\/JB.181.4.1364-1368.1999","article-title":"The virulence plasmid of Salmonella typhimurium is self-transmissible","volume":"181","author":"Ahmer","year":"1999","journal-title":"J Bacteriol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1006\/plas.1994.1012","article-title":"Nucleotide sequence and replication 845 characteristics of RepHI1B: A replicon specific to the IncHI1 plasmids","volume":"846","author":"Gabant","year":"1994","journal-title":"Plasmid"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"e00105-18","DOI":"10.1128\/mBio.00105-18","article-title":"Emergence of an Extensively Drug-Resistant Salmonella enterica Serovar Typhi clone harboring a promiscuous plasmid encoding resistance to fluoroquinolones and third-generation cephalosporins","volume":"9","author":"Klemm","year":"2018","journal-title":"MBio"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1111\/jam.15211","article-title":"Identification and characterization of multidrug-resistant ESBL-producing Salmonella enterica serovars Kentucky and Typhimurium isolated in Tunisia CTX-M-61\/TEM-34, a novel cefotaxime-hydrolysing \u03b2-lactamase of Salmonella","volume":"132","author":"Belghouthi","year":"2022","journal-title":"J. Appl. Microbiol."},{"key":"ref_95","first-page":"4610246","article-title":"Typhoid fever due to extended spectrum \u03b2- lactamase-producing Salmonella enterica serovar Typhi: A case report and literature review","volume":"2018","author":"Riyaaz","year":"2018","journal-title":"Case Rep. Infect. Dis."},{"key":"ref_96","first-page":"535","article-title":"Molecular detection of integrin and antimicrobial substances genes in multidrug resistant Salmonella isolated from poultry, calves and human in Beni-Suef governorate, Egypt","volume":"7","author":"Shany","year":"2018","journal-title":"Beni-Suef Univ. J. Basic Appl. Sci."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Odoch, T., Sekse, C., Abee-Lund, T.M., Hansen, H.H.C., Kankya, C., and Wasteson, Y. (2018). Diversity and antimicrobial resistance genotypes in non-typhoidal Salmonella isolates from poultry farms in Uganda. Int. J. Environ. Res. Public Health, 15.","DOI":"10.3390\/ijerph15020324"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Kim, C., Latif, I., Neupane, D.P., Lee, G.Y., Kwon, R.S., Batool, A., Ahmed, Q., Qamar, M.U., and Song, J. (2021). The molecular basis of extensively drug-resistant Salmonella Typhi isolates from pediatric septicemia patients. PLoS ONE, 16.","DOI":"10.1101\/2021.06.20.449163"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Awad, W., Hess, C., and Hess, M. (2017). Enteric pathogens and their toxin-induced disruption of the intestinal barrier through alteration of tight junctions in chickens. Toxins, 9.","DOI":"10.3390\/toxins9020060"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Paradis, T., B\u00e8gue, H., Basmaciyan, L., Dalle, F., and Bon, F. (2021). Tight junctions as a key for pathogens invasion in intestinal epithelial cells. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052506"},{"key":"ref_101","first-page":"872","article-title":"Disruption of epithelial barrier integrity by Salmonella enterica serovar Typhimurium requires geranylgeranylated proteins","volume":"71","author":"Tafazoli","year":"2003","journal-title":"Am. Soc. Microbiol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1017\/S0950268800058088","article-title":"Infecting dose and severity of typhoid: Analysis of volunteer data and examination of the influence of the definition of illness used","volume":"115","author":"Glynn","year":"1995","journal-title":"Epidemiol. Infect."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1093\/cid\/ciu078","article-title":"An outpatient, ambulant design, controlled human infection model using escalating doses of Salmonella Typhi challenge delivered in sodium bicarbonate solution","volume":"58","author":"Waddington","year":"2014","journal-title":"Clin. Infect. Dis."},{"key":"ref_104","first-page":"604","article-title":"Asymptomatic typhoidal bacteremia in volunteers","volume":"161","author":"Snyder","year":"1963","journal-title":"Antimicrob. Agents Chemotherap."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"270","DOI":"10.3389\/fcimb.2019.00270","article-title":"Salmonella Pathogenicity Island 1 (SPI-1) and its complex regulatory network","volume":"9","author":"Lou","year":"2019","journal-title":"Front. Cell Infect. Microbiol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1186\/s12866-021-02187-1","article-title":"Investigation of the invasion mechanism mediated by the outer membrane protein PagN of Salmonella Typhimurium","volume":"21","author":"Barilleau","year":"2021","journal-title":"BMC Microbiol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"2894","DOI":"10.1128\/IAI.69.5.2894-2901.2001","article-title":"Salmonella enterica serovar Typhi possesses a unique repertoire of fimbrial gene sequences","volume":"69","author":"Townsend","year":"2001","journal-title":"Infect. Immun."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1128\/IAI.69.1.204-212.2001","article-title":"Salmonella enterica serotype Typhimurium elicits cross-immunity against a Salmonella enterica serotype enteritidis strain expressing LP fimbriae from the lac promoter","volume":"69","author":"Nicholson","year":"2001","journal-title":"Infect Immun."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"3067","DOI":"10.1128\/IAI.68.6.3067-3073.2000","article-title":"Salmonella enterica serovar Typhi uses type IVB pili to enter human intestinal epithelial cells","volume":"68","author":"Zhang","year":"2000","journal-title":"Infect Immun."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1046\/j.1365-2958.2000.01907.x","article-title":"Host adaptation and the emergence of infectious disease: The Salmonella paradigm","volume":"36","author":"Kingsley","year":"2000","journal-title":"Mol. Microbiol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1097\/00006454-200012000-00016","article-title":"Nontyphoidal Salmonella infections of children in tropical Africa","volume":"19","author":"Graham","year":"2000","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1172\/JCI11792","article-title":"Breaching the mucosal barrier by stealth: An emerging pathogenic mechanism for enteroadherent bacterial pathogens","volume":"107","author":"Fleckenstein","year":"2001","journal-title":"J. Clin. Investig."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1146\/annurev.med.52.1.259","article-title":"Salmonella: A model for bacterial pathogenesis","volume":"52","author":"Ohl","year":"2001","journal-title":"Annu. Rev. Med."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1172\/JCI10501","article-title":"Salmonella typhimurium translocates flagellin across intestinal epithelia, inducing a proinflammatory response","volume":"107","author":"Gewirtz","year":"2001","journal-title":"J. Clin. Investig."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1128\/iai.65.2.395-404.1997","article-title":"Salmonella typhi stimulation of human intestinal epithelial cells induces secretion of epithelial cell-derived interleukin 6","volume":"65","author":"Weinstein","year":"1997","journal-title":"Infect Immun."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1086\/503033","article-title":"Salmonella enterica serovar Paratyphi A and S. enterica serovar Typhi cause indistinguishable clinical syndromes in Kathmandu, Nepal","volume":"42","author":"Maskey","year":"2006","journal-title":"Clin. Infect. Dis."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"110008","DOI":"10.1098\/rsob.110008","article-title":"Combined high-resolution genotyping and geospatial analysis reveals modes of endemic urban typhoid fever transmission","volume":"1","author":"Baker","year":"2011","journal-title":"Open Biol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1097\/QCO.0000000000000479","article-title":"Typhoid and paratyphoid fever: A call to action","volume":"31","author":"Gibani","year":"2018","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Liaquat, S., Sarwar, Y., Ali, A., Haque, A., Farooq, M., Martinez-Ballesteros, I., Laorden, L., Garaizar, J., and Bikandi, J. (2018). Virulotyping of Salmonella enterica serovar Typhi isolates from Pakistan: Absence of complete SPI10 in Vi negative isolates. PLoS Negl. Trop. Dis., 12.","DOI":"10.1371\/journal.pntd.0006839"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.micres.2011.08.001","article-title":"Role of antigens and virulence factors of Salmonella enterica serovar Typhi in its pathogenesis","volume":"167","author":"Kaur","year":"2012","journal-title":"Microbiol. Res."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.mib.2012.11.006","article-title":"Salmonella T3SSs: Successful mission of the secret(ion) agents","volume":"16","author":"Moest","year":"2013","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"2310","DOI":"10.1128\/IAI.66.5.2310-2318.1998","article-title":"Differential early interactions between Salmonella enterica serovar Typhi and two other pathogenic Salmonella serovars with intestinal epithelial cells","volume":"66","author":"Weinstein","year":"1998","journal-title":"Infect. Immun."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"14084","DOI":"10.1074\/jbc.275.19.14084","article-title":"Analysis by high density cDNA arrays of altered gene expression in human intestinal epithelial cells in response to infection with the invasive enteric bacteria Salmonella","volume":"275","author":"Eckmann","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"5894","DOI":"10.4049\/jimmunol.164.11.5894","article-title":"Salmonella Typhimurium infection and lipopolysaccharide stimulation induce similar changes in macrophage gene expression","volume":"164","author":"Rosenberger","year":"2000","journal-title":"J. Immunol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1046\/j.1462-5822.2000.00056.x","article-title":"Pathogen-induced apoptosis of macrophages: A common end for different pathogenic strategies","volume":"2","author":"Navarre","year":"2000","journal-title":"Cell Microbiol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1046\/j.1365-2958.2000.02103.x","article-title":"Salmonella induces macrophage death by caspase-1-dependent necrosis","volume":"38","author":"Brennan","year":"2000","journal-title":"Mol. Microbiol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/S0966-842X(00)01937-5","article-title":"Salmonella-induced cell death: Apoptosis, necrosis or programmed cell death?","volume":"9","author":"Boise","year":"2001","journal-title":"Trends. Microbiol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1084\/jem.192.2.249","article-title":"Salmonella exploits caspase-1 to colonize Peyer\u2019s patches in a murine typhoid model","volume":"192","author":"Monack","year":"2000","journal-title":"J. Exp. Med."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1097\/00001432-200110000-00011","article-title":"Typhoid fever: Pathogenesis and disease","volume":"14","author":"House","year":"2001","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Mascellino, M.T. (2018). Virulence system of Salmonella with special reference to Salmonella enterica. Salmonella\u2014A Re-Emerging Pathogen, IntechOpen.","DOI":"10.5772\/intechopen.69799"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.femsim.2005.02.002","article-title":"Distribution of \u201cclassic\u201d virulence factors among Salmonella spp.","volume":"44","author":"Aphons","year":"2005","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.3389\/fmicb.2016.01305","article-title":"Relevant genes linked to virulence are required for Salmonella Typhimurium to survive intracellularly in the social amoeba dictyosteliumdiscoideum","volume":"7","author":"Riquelme","year":"2016","journal-title":"Front. Microbiol."},{"key":"ref_133","first-page":"13","article-title":"The mechanisms of virulence and antimicrobial resistance in Salmonella enterica serovar Typhi: A systematic review","volume":"2","author":"Fowoyo","year":"2020","journal-title":"Afr. J. Bio. Sci."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Hart, P.J., O\u2019Shaughnessy, C.M., Siggins, M.K., Bobat, S., Kingsley, R.A., Goulding, D.A., Crump, J.A., Reyburn, H., Micoli, F., and Dougan, G. (2016). Differential killing of Salmonella enterica Serovar Typhi by antibodies targeting Vi and lipopolysaccharide O:9 antigen. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0145945"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"3367","DOI":"10.1128\/IAI.73.6.3367-3374.2005","article-title":"The Vi capsular antigen of Salmonella enterica serotype Typhi reduces toll-like receptor-dependent Interleukin-8 expression in the intestinal mucosa","volume":"73","author":"Raffatellu","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1038\/35101607","article-title":"Complete genome sequence of a multiple drug resistant Salmonella enterica serovar Typhi CT18","volume":"413","author":"Parkhill","year":"2001","journal-title":"Nature"}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/10\/10\/2006\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:50:04Z","timestamp":1760143804000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/10\/10\/2006"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,11]]},"references-count":136,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["microorganisms10102006"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms10102006","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,11]]}}}