Klemm EJ et al., 2018. Emergence of an extensively drug-resistant Salmonella enterica serovar Typhi clone harboring a promiscuous plasmid encoding resistance to fluoroquinolones and third-generation cephalosporins. mBio 9: 1–10.
Nizamuddin S, Ching C, Kamal R, Zaman MH, Sultan F, 2017. Continued outbreak of ceftriaxone-resistant Salmonella enterica serotype Typhi across Pakistan and assessment of knowledge and practices among healthcare workers. Am J Trop Med Hyg 104: 1265–1270.
Wong VK et al., 2015. Phylogeographical analysis of the dominant multidrug-resistant H58 clade of Salmonella typhi identifies inter- and intracontinental transmission events. Nat Genet 47: 632–639.
Chatham-Stephens K et al., 2019. Emergence of extensively drug-resistant Salmonella typhi infections among travelers to or from Pakistan–United States, 2016–2018. MMWR Morb Mortal Wkly Rep 38: 630.
World Health Organization , 2018. 2018 - Pakistan. Available at: https://www.who.int/emergencies/disease-outbreak-news/item/27-december-2018-typhoid-pakistan-en. Accessed October 23, 2022.
Nair S et al., 2021. ESBL-producing strains isolated from imported cases of enteric fever in England and Wales reveal multiple chromosomal integrations of blaCTX-M-15 in XDR Salmonella typhi. J Antimicrob Chemother 76: 1459–1466.
Wong VK et al., 2016. An extended genotyping framework for Salmonella enterica serovar Typhi, the cause of human typhoid. Nat Commun 7: 1–11.
Ingle DJ, Nair S, Hartman H, Ashton PM, Dyson ZA, Day M, Freedman J, Chattaway MA, Holt KE, Dallman TJ, 2019. Informal genomic surveillance of regional distribution of Salmonella typhi genotypes and antimicrobial resistance via returning travellers. PLoS Negl Trop Dis 13: 1–20.
Ingle DJ et al., 2021. Genomic epidemiology and antimicrobial resistance mechanisms of imported typhoid in Australia. Antimicrob Agents Chemother 65: 1–12.
Qamar FN et al., 2018. 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. Lancet Infect Dis 18: 1368–1376.
Tagg KA et al., 2020. Sequencing and characterization of five extensively drug-resistant Salmonella enterica serotype Typhi isolates implicated in human infections from Punjab, Pakistan. Microbiol Resour Announc 9: 9–11.
Clinical and Laboratory Standards Institute , 2018. M02 Performance Standards for Antimicrobial Disk Susceptibility Tests, 13th edition. Available at: https://clsi.org/standards/products/microbiology/documents/m02/. Accessed November 3, 2022.
Wohl S, Lee EC, DiPrete BL, Lessler J, 2022. Sample size calculations for variant surveillance in the presence of biological and systematic biases. medRxiv. Available at: https://www.medrxiv.org/content/10.1101/2021.12.30.21268453v1. Accessed October 23, 2022.
Karimnasab N, Tadayon K, Khaki P, Bidhendi SM, Ghaderi R, Sekhavati M, Asadi F, 2013. An optimized affordable DNA-extraction method from Salmonella enterica enteritidis for PCR experiments. Arch Razi Inst 68: 105–109.
Florensa AF, Kaas RS, Clausen PTLC, Aytan-Aktug D, Aarestrup FM, 2022. ResFinder: an open online resource for identification of antimicrobial resistance genes in next-generation sequencing data and prediction of phenotypes from genotypes. Microb Genom 8: 1–10.
Carattoli A, Zankari E, Garciá-Fernández A, Larsen MV, Lund O, Villa L, Aarestrup FM, Hasman H, 2014. In silico detection and typing of plasmids using PlasmidFinder and plasmid multilocus sequence typing. Antimicrob Agents Chemother 58: 3895–3903.
Harrison KJ, De Crécy-Lagard V, Zallot R, 2018. Gene Graphics: a genomic neighborhood data visualization web application. Bioinformatics 34: 1406–1408.
Kaas RS, Leekitcharoenphon P, Aarestrup FM, Lund O, 2014. Solving the problem of comparing whole bacterial genomes across different sequencing platforms. PLoS One 9: 1–8.
Alonso-del Valle A, León-Sampedro R, Rodríguez-Beltrán J, DelaFuente J, Hernández-García M, Ruiz-Garbajosa P, Cantón R, Peña-Miller R, San Millán A, 2021. Variability of plasmid fitness effects contributes to plasmid persistence in bacterial communities. Nat Commun 12: 1–14.
Kamruzzaman M, Iredell J, 2019. A ParDE-family toxin antitoxin system in major resistance plasmids of Enterobacteriaceae confers antibiotic and heat tolerance. Sci Rep 9: 1–12.
Goldfarb T, Sberro H, Weinstock E, Cohen O, Doron S, Charpak‐Amikam Y, Afik S, Ofir G, Sorek R, 2015. BREX is a novel phage resistance system widespread in microbial genomes. EMBO J 34: 169–183.
Fronzes R, Christie PJ, Waksman G, 2009. The structural biology of type IV secretion systems. Nat Rev Microbiol 7: 703–714.
Andrews JR, Qamar FN, Charles RC, Ryan E, 2018. Extensively drug-resistant typhoid: are conjugate vaccines arriving just in time? N Engl J Med 379: 1491–1493.
Collineau L et al., 2019. Integrating whole-genome sequencing data into quantitative risk assessment of foodborne antimicrobial resistance: a review of opportunities and challenges. Front Microbiol 10: 1–18.
Lazebnik T, Bunimovich-Mendrazitsky S, 2022. Generic approach for mathematical model of multi-strain pandemics. PLoS One 17: 1–20.
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Abstract Views | 4544 | 2615 | 172 |
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Typhoid fever, caused by Salmonella enterica serovar Typhi (S. Typhi), is a life-threatening bacterial infection. Recently, an outbreak of a new sublineage of extensively drug resistant (XDR) S. Typhi emerged in Pakistan in the province of Sindh. This sublineage had both a composite multidrug resistance transposon integrated on the chromosome and an acquired IncY plasmid carrying the extended spectrum beta-lactamase, blaCTX-M-15, which conferred resistance to third-generation cephalosporins. We observed previously that XDR typhoid had spread beyond the originating southern Sindh Province. Thus, we sought to determine the genetic diversity of 58 ceftriaxone-resistant S. Typhi clinical isolates by whole genome sequencing collected across Pakistan from November 2018 to December 2020 to provide insights into the molecular epidemiology of the evolving outbreak. We identify multiple novel genomic integrations of the extended spectrum beta-lactamase gene into the chromosome in S. Typhi, revealing the existence of various XDR typhoid variants circulating in the country. Notably, the integration of the IncY plasmid bearing antibiotic resistance genes may allow for subsequent plasmid acquisition by these variants, potentially leading to further plasmid-borne multidrug resistance. Our results can inform containment initiatives, help track associated outcomes and international spread, and help determine how widespread the risk is.
These authors contributed equally to this work.
Financial support: This work was funded by a research grant from the Shaukat Khanum Memorial Cancer Hospital and Research Centre.
Disclaimer: This study was granted exemption from the Shaukat Khanum Memorial Cancer Hospital and Research Centre’s Institutional Review Board.
Authors addresses: Rashid Kamal, Faisal Sultan, Salma Abbas, and Summiya Nizamuddin, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, E-mails: dr.rashidkamal@gmail.com, faisal@skm.org.pk, salmaabbas@skm.org.pk, and summiyan@skm.org.pk. Carly Ching and Muhammad H. Zaman, Department of Biomedical Engineering, Boston University, Boston, MA, E-mails: chingc@bu.edu and zaman@bu.edu. Ezza Khan and Shaper Mirza, Department of Biology, Syed Babar Ali School of Science and Engineering, Lahore University of Management Sciences, Lahore, Pakistan, E-mails: ezzakhan283@gmail.com and shaper.mirza@lums.edu.pk.
Klemm EJ et al., 2018. Emergence of an extensively drug-resistant Salmonella enterica serovar Typhi clone harboring a promiscuous plasmid encoding resistance to fluoroquinolones and third-generation cephalosporins. mBio 9: 1–10.
Nizamuddin S, Ching C, Kamal R, Zaman MH, Sultan F, 2017. Continued outbreak of ceftriaxone-resistant Salmonella enterica serotype Typhi across Pakistan and assessment of knowledge and practices among healthcare workers. Am J Trop Med Hyg 104: 1265–1270.
Wong VK et al., 2015. Phylogeographical analysis of the dominant multidrug-resistant H58 clade of Salmonella typhi identifies inter- and intracontinental transmission events. Nat Genet 47: 632–639.
Chatham-Stephens K et al., 2019. Emergence of extensively drug-resistant Salmonella typhi infections among travelers to or from Pakistan–United States, 2016–2018. MMWR Morb Mortal Wkly Rep 38: 630.
World Health Organization , 2018. 2018 - Pakistan. Available at: https://www.who.int/emergencies/disease-outbreak-news/item/27-december-2018-typhoid-pakistan-en. Accessed October 23, 2022.
Nair S et al., 2021. ESBL-producing strains isolated from imported cases of enteric fever in England and Wales reveal multiple chromosomal integrations of blaCTX-M-15 in XDR Salmonella typhi. J Antimicrob Chemother 76: 1459–1466.
Wong VK et al., 2016. An extended genotyping framework for Salmonella enterica serovar Typhi, the cause of human typhoid. Nat Commun 7: 1–11.
Ingle DJ, Nair S, Hartman H, Ashton PM, Dyson ZA, Day M, Freedman J, Chattaway MA, Holt KE, Dallman TJ, 2019. Informal genomic surveillance of regional distribution of Salmonella typhi genotypes and antimicrobial resistance via returning travellers. PLoS Negl Trop Dis 13: 1–20.
Ingle DJ et al., 2021. Genomic epidemiology and antimicrobial resistance mechanisms of imported typhoid in Australia. Antimicrob Agents Chemother 65: 1–12.
Qamar FN et al., 2018. 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. Lancet Infect Dis 18: 1368–1376.
Tagg KA et al., 2020. Sequencing and characterization of five extensively drug-resistant Salmonella enterica serotype Typhi isolates implicated in human infections from Punjab, Pakistan. Microbiol Resour Announc 9: 9–11.
Clinical and Laboratory Standards Institute , 2018. M02 Performance Standards for Antimicrobial Disk Susceptibility Tests, 13th edition. Available at: https://clsi.org/standards/products/microbiology/documents/m02/. Accessed November 3, 2022.
Wohl S, Lee EC, DiPrete BL, Lessler J, 2022. Sample size calculations for variant surveillance in the presence of biological and systematic biases. medRxiv. Available at: https://www.medrxiv.org/content/10.1101/2021.12.30.21268453v1. Accessed October 23, 2022.
Karimnasab N, Tadayon K, Khaki P, Bidhendi SM, Ghaderi R, Sekhavati M, Asadi F, 2013. An optimized affordable DNA-extraction method from Salmonella enterica enteritidis for PCR experiments. Arch Razi Inst 68: 105–109.
Florensa AF, Kaas RS, Clausen PTLC, Aytan-Aktug D, Aarestrup FM, 2022. ResFinder: an open online resource for identification of antimicrobial resistance genes in next-generation sequencing data and prediction of phenotypes from genotypes. Microb Genom 8: 1–10.
Carattoli A, Zankari E, Garciá-Fernández A, Larsen MV, Lund O, Villa L, Aarestrup FM, Hasman H, 2014. In silico detection and typing of plasmids using PlasmidFinder and plasmid multilocus sequence typing. Antimicrob Agents Chemother 58: 3895–3903.
Harrison KJ, De Crécy-Lagard V, Zallot R, 2018. Gene Graphics: a genomic neighborhood data visualization web application. Bioinformatics 34: 1406–1408.
Kaas RS, Leekitcharoenphon P, Aarestrup FM, Lund O, 2014. Solving the problem of comparing whole bacterial genomes across different sequencing platforms. PLoS One 9: 1–8.
Alonso-del Valle A, León-Sampedro R, Rodríguez-Beltrán J, DelaFuente J, Hernández-García M, Ruiz-Garbajosa P, Cantón R, Peña-Miller R, San Millán A, 2021. Variability of plasmid fitness effects contributes to plasmid persistence in bacterial communities. Nat Commun 12: 1–14.
Kamruzzaman M, Iredell J, 2019. A ParDE-family toxin antitoxin system in major resistance plasmids of Enterobacteriaceae confers antibiotic and heat tolerance. Sci Rep 9: 1–12.
Goldfarb T, Sberro H, Weinstock E, Cohen O, Doron S, Charpak‐Amikam Y, Afik S, Ofir G, Sorek R, 2015. BREX is a novel phage resistance system widespread in microbial genomes. EMBO J 34: 169–183.
Fronzes R, Christie PJ, Waksman G, 2009. The structural biology of type IV secretion systems. Nat Rev Microbiol 7: 703–714.
Andrews JR, Qamar FN, Charles RC, Ryan E, 2018. Extensively drug-resistant typhoid: are conjugate vaccines arriving just in time? N Engl J Med 379: 1491–1493.
Collineau L et al., 2019. Integrating whole-genome sequencing data into quantitative risk assessment of foodborne antimicrobial resistance: a review of opportunities and challenges. Front Microbiol 10: 1–18.
Lazebnik T, Bunimovich-Mendrazitsky S, 2022. Generic approach for mathematical model of multi-strain pandemics. PLoS One 17: 1–20.
Past two years | Past Year | Past 30 Days | |
---|---|---|---|
Abstract Views | 4544 | 2615 | 172 |
Full Text Views | 511 | 62 | 9 |
PDF Downloads | 277 | 41 | 4 |