1887

Abstract

Non-typhoidal associated with multidrug resistance cause invasive disease in sub-Saharan Africa. Specific lineages of serovars Typhimurium and Enteritidis have been implicated. Here we characterized the genomic diversity of 100 clinical non-typhoidal collected from 93 patients in 2001 from the eastern, and in 2006–2018 from the western regions of The Gambia respectively. A total of 93 isolates (64 invasive, 23 gastroenteritis and six other sites) representing a single infection episode were phenotypically tested for antimicrobial susceptibility using the Kirby–Bauer disc diffusion technique. Whole genome sequencing of 100 isolates was performed using Illumina, and the reads were assembled and analysed using SPAdes. The Typing Resource (SISTR) was used for serotyping. SNP differences among the 93 isolates were determined using Roary, and phylogenetic analysis was performed in the context of 495 African strains from the European Nucleotide Archive. serovars Typhimurium (26/64; 30.6 %) and Enteritidis (13/64; 20.3 %) were associated with invasive disease, whilst other serovars were mainly responsible for gastroenteritis (17/23; 73.9 %). The presence of three major serovar Enteritidis clades was confirmed, including the invasive West African clade, which made up more than half (11/16; 68.8 %) of the genomes. Multidrug resistance was confined among the serovar Enteritidis West African clade. The presence of this epidemic virulent clade has potential for spread of resistance and thus important implications for systematic patient management. Surveillance and epidemiological investigations to inform control are warranted.

Funding
This study was supported by the:
  • Medical Research Charities Group
    • Principle Award Recipient: SaffiatouDarboe
  • the Global Challenges Research Fund (GCRF) data & resources grant (Award BBS/OS/GC/000009D)
    • Principle Award Recipient: BlancaPerez-Sepulveda
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
Loading

Article metrics loading...

/content/journal/mgen/10.1099/mgen.0.000785
2022-03-18
2022-07-06
Loading full text...

Full text loading...

/deliver/fulltext/mgen/8/3/mgen000785.html?itemId=/content/journal/mgen/10.1099/mgen.0.000785&mimeType=html&fmt=ahah

References

  1. Feasey NA, Hadfield J, Keddy KH, Dallman TJ, Jacobs J et al. Distinct Salmonella Enteritidis lineages associated with enterocolitis in high-income settings and invasive disease in low-income settings. Nat Genet 2016; 48:1211–1217 [View Article] [PubMed]
    [Google Scholar]
  2. Jones TF, Ingram LA, Cieslak PR, Vugia DJ, Tobin-D’Angelo M et al. Salmonellosis outcomes differ substantially by serotype. J Infect Dis 2008; 198:109–114 [View Article] [PubMed]
    [Google Scholar]
  3. Miller RA, Wiedmann M. The cytolethal distending toxin produced by nontyphoidal Salmonella serotypes javiana, montevideo, oranienburg, and mississippi induces DNA damage in a manner similar to that of serotype typhi. mBio 2016; 7:e02109-16 [View Article] [PubMed]
    [Google Scholar]
  4. van Asten AJ, van Dijk JE. Distribution of “classic” virulence factors among Salmonella spp. FEMS Immunol Med Microbiol 2005; 44:251–259 [View Article] [PubMed]
    [Google Scholar]
  5. Langridge GC, Fookes M, Connor TR, Feltwell T, Feasey N et al. Patterns of genome evolution that have accompanied host adaptation in Salmonella. Proc Natl Acad Sci U S A 2015; 112:863–868 [View Article] [PubMed]
    [Google Scholar]
  6. Majowicz SE, Musto J, Scallan E, Angulo FJ, Kirk M et al. The global burden of nontyphoidal Salmonella gastroenteritis. Clin Infect Dis 2010; 50:882–889 [View Article] [PubMed]
    [Google Scholar]
  7. Gal-Mor O, Boyle EC, Grassl GA et al. Same species, different diseases: how and why typhoidal and non-typhoidal Salmonella enterica serovars differ. Front Microbiol 2014; 5:391 [View Article] [PubMed]
    [Google Scholar]
  8. Onwuezobe IA, Oshun PO, Odigwe CC. Antimicrobials for treating symptomatic non-typhoidal Salmonella infection. Cochrane Database Syst Rev 2012; 11:CD001167 [View Article] [PubMed]
    [Google Scholar]
  9. Crump JA, Sjölund-Karlsson M, Gordon MA, Parry CM et al. Epidemiology, clinical presentation, laboratory diagnosis, antimicrobial resistance, and antimicrobial management of invasive Salmonella infections. Clin Microbiol Rev 2015; 28:901–937 [View Article] [PubMed]
    [Google Scholar]
  10. Ao TT, Feasey NA, Gordon MA, Keddy KH, Angulo FJ et al. Global burden of invasive nontyphoidal Salmonella disease, 2010(1). Emerg Infect Dis 2015; 21: [View Article] [PubMed]
    [Google Scholar]
  11. Okoro CK, Kingsley RA, Connor TR, Harris SR, Parry CM et al. Intracontinental spread of human invasive Salmonella Typhimurium pathovariants in sub-Saharan Africa. Nat Genet 2012; 44:1215–1221 [View Article] [PubMed]
    [Google Scholar]
  12. Feasey NA, Dougan G, Kingsley RA, Heyderman RS, Gordon MA et al. Invasive non-typhoidal Salmonella disease: an emerging and neglected tropical disease in Africa. Lancet 2012; 379:2489–2499 [View Article] [PubMed]
    [Google Scholar]
  13. Stanaway JD, Parisi A et al. The global burden of non-typhoidal Salmonella invasive disease: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Infect Dis 2019; 19:1312–1324 [View Article] [PubMed]
    [Google Scholar]
  14. Kingsley RA, Msefula CL, Thomson NR, Kariuki S, Holt KE et al. Epidemic multiple drug resistant Salmonella Typhimurium causing invasive disease in sub-Saharan Africa have a distinct genotype. Genome Res 2009; 19:2279–2287 [View Article] [PubMed]
    [Google Scholar]
  15. Okoro CK, Kingsley RA, Barquist L, Simon HR, Connor TR et al. Invasive Salmonella typhimurium populations from Sub-Saharan Africa: Transmission and adaptation dynamics. Int J Infect Dis 2014; 21:342 [View Article]
    [Google Scholar]
  16. Okoro CK, Barquist L, Connor TR, Harris SR, Clare S et al. Correction: signatures of adaptation in human invasive Salmonella Typhimurium ST313 populations from Sub-Saharan Africa. PLoS Negl Trop Dis 2015; 9:e0003848 [View Article] [PubMed]
    [Google Scholar]
  17. Van Puyvelde S, Pickard D, Vandelannoote K, Heinz E, Barbé B et al. An African Salmonella Typhimurium ST313 sublineage with extensive drug-resistance and signatures of host adaptation. Nat Commun 2019; 10:1–12 [View Article] [PubMed]
    [Google Scholar]
  18. Pulford CV, Perez-Sepulveda BM, Canals R, Bevington JA, Bengtsson RJ et al. Stepwise evolution of Salmonella Typhimurium ST313 causing bloodstream infection in Africa. Nat Microbiol 2021; 6:327–338 [View Article] [PubMed]
    [Google Scholar]
  19. Lunguya O, Lejon V, Phoba M-F, Bertrand S, Vanhoof R et al. Antimicrobial resistance in invasive non-typhoid Salmonella from the Democratic Republic of the Congo: emergence of decreased fluoroquinolone susceptibility and extended-spectrum beta lactamases. PLoS Negl Trop Dis 2013; 7:e2103 [View Article] [PubMed]
    [Google Scholar]
  20. Darboe S, Okomo U, Muhammad A-K, Ceesay B, Jallow M et al. Community-acquired invasive bacterial disease in urban Gambia, 2005-2015: A hospital-based surveillance. Clin Infect Dis 2019; 69:S105–S113 [View Article] [PubMed]
    [Google Scholar]
  21. Enwere G, Biney E, Cheung YB, Zaman SMA, Okoko B et al. Epidemiologic and clinical characteristics of community-acquired invasive bacterial infections in children aged 2-29 months in The Gambia. Pediatr Infect Dis J 2006; 25:700–705 [View Article] [PubMed]
    [Google Scholar]
  22. Hill PC, Onyeama CO, Ikumapayi UNA, Secka O, Ameyaw S et al. Bacteraemia in patients admitted to an urban hospital in West Africa. BMC Infect Dis 2007; 7:2–10 [View Article] [PubMed]
    [Google Scholar]
  23. Kwambana-Adams B, Darboe S, Nabwera H, Foster-Nyarko E, Ikumapayi UN et al. Salmonella infections in The Gambia, 2005-2015. Clin Infect Dis 2015; 61 Suppl 4:S354–62 [View Article] [PubMed]
    [Google Scholar]
  24. Ikumapayi UN, Antonio M, Sonne-Hansen J, Biney E, Enwere G et al. Molecular epidemiology of community-acquired invasive non-typhoidal Salmonella among children aged 2 29 months in rural Gambia and discovery of a new serovar, Salmonella enterica Dingiri. J Med Microbiol 2007; 56:1479–1484 [View Article] [PubMed]
    [Google Scholar]
  25. The Gambia Bureau Statistics The Gambia Demographic and Health Survey 2014 p 5
    [Google Scholar]
  26. Ceesay SJ, Casals-Pascual C, Nwakanma DC, Walther M, Gomez-Escobar N et al. Continued decline of malaria in The Gambia with implications for elimination. PLoS One 2010; 5:e12242 [View Article] [PubMed]
    [Google Scholar]
  27. UNICEF, WHO, World Bank Prevalence of underweight, weight for age. Joint child malnutrition estimates (JME); 2013 https://data.worldbank.org/indicator/SH.STA.MALN.ZS?locations=GM accessed 27 July 2020
  28. National AIDS Secretariat The Gambia Global AIDS Response Progress Report; 2015 https://www.unaids.org/sites/default/files/country/documents/GMB_narrative_report_2015.pdf
  29. Clinical and Laboratory Standards Institute Performance standards for antimicrobial susceptibility testing; 2017M100–S27
  30. Perez-Sepulveda BM, Heavens D, Pulford CV, Predeus AV, Low R et al. An accessible, efficient and global approach for the large-scale sequencing of bacterial genomes. Microbiology 2020 [View Article]
    [Google Scholar]
  31. Wingett SW, Andrews S. FASTQ Screen: A tool for multi-genome mapping and quality control. F1000Res 2018; 7:1338 [View Article] [PubMed]
    [Google Scholar]
  32. Bolger AM, Lohse M, Usadel B et al. Trimmomatic: A flexible trimmer for Illumina sequence data. Bioinformatics 2014; 30:2114–2120 [View Article] [PubMed]
    [Google Scholar]
  33. Bankevich A, Nurk S, Antipov D, Gurevich AA, Dvorkin M et al. SPAdes: A new genome assembly algorithm and its applications to single-cell sequencing. J Comput Biol 2012; 19:455–477 [View Article] [PubMed]
    [Google Scholar]
  34. Yoshida C, Brumwell SL, Lingohr EJ, Ahmad A, Blimkie TM et al. Draft whole-genome sequences of 25 Salmonella enterica strains representing 24 serovars. Genome Announc 2016; 4:e01718-15 [View Article] [PubMed]
    [Google Scholar]
  35. Alikhan N-F, Zhou Z, Sergeant MJ, Achtman M et al. A genomic overview of the population structure of Salmonella. PLOS Genet 2018; 14:e1007261 [View Article] [PubMed]
    [Google Scholar]
  36. Achtman M, Wain J, Weill F-X, Nair S, Zhou Z et al. Multilocus sequence typing as a replacement for serotyping in Salmonella enterica. PLoS Pathog 2012; 8:e1002776 [View Article] [PubMed]
    [Google Scholar]
  37. Seemann T. Prokka: rapid prokaryotic genome annotation. Bioinformatics 2014; 30:2068–2069 [View Article] [PubMed]
    [Google Scholar]
  38. Page AJ, Cummins CA, Hunt M, Wong VK, Reuter S et al. Roary: rapid large-scale prokaryote pan genome analysis. Bioinformatics 2015; 31:3691–3693 [View Article] [PubMed]
    [Google Scholar]
  39. Katoh K, Misawa K, Kuma K, Miyata T. MAFFT: A novel method for rapid multiple sequence alignment based on fast Fourier transform. Nucleic Acids Res 2002; 30:3059–3066 [View Article] [PubMed]
    [Google Scholar]
  40. Letunic I, Bork P. Interactive tree of life (iTOL) v3: an online tool for the display and annotation of phylogenetic and other trees. Nucleic Acids Res 2016; 44:W242–5 [View Article] [PubMed]
    [Google Scholar]
  41. Zankari E, Hasman H, Cosentino S, Vestergaard M, Rasmussen S et al. Identification of acquired antimicrobial resistance genes. J Antimicrob Chemother 2012; 67:2640–2644 [View Article] [PubMed]
    [Google Scholar]
  42. Carattoli A, Zankari E, García-Fernández A, Voldby Larsen M, Lund O et al. In silico detection and typing of plasmids using PlasmidFinder and plasmid multilocus sequence typing. Antimicrob Agents Chemother 2014; 58:3895–3903 [View Article] [PubMed]
    [Google Scholar]
  43. Chen L, Yang J, Yu J, Yao Z, Sun L et al. VFDB: A reference database for bacterial virulence factors. Nucleic Acids Res 2005; 33:D325–8 [View Article] [PubMed]
    [Google Scholar]
  44. García-Fernández A, Villa L, Moodley A, Hasman H, Miriagou V et al. Multilocus sequence typing of IncN plasmids. J Antimicrob Chemother 2011; 66:1987–1991 [View Article] [PubMed]
    [Google Scholar]
  45. Aldrich C, Hartman H, Feasey N, Chattaway MA, Dekker D et al. Emergence of phylogenetically diverse and fluoroquinolone resistant Salmonella Enteritidis as a cause of invasive nontyphoidal Salmonella disease in Ghana. PLoS Negl Trop Dis 2019; 13:e0007485 [View Article] [PubMed]
    [Google Scholar]
  46. Schim van der Loeff MF, Sarge-Njie R, Ceesay S, Awasana AA, Jaye P et al. Regional differences in HIV trends in The Gambia: results from sentinel surveillance among pregnant women. AIDS 2003; 17:1841–1846 [View Article] [PubMed]
    [Google Scholar]
  47. Mwesigwa J, Okebe J, Affara M, Di Tanna GL, Nwakanma D et al. On-going malaria transmission in The Gambia despite high coverage of control interventions: A nationwide cross-sectional survey. Malar J 2015; 14:314 [View Article] [PubMed]
    [Google Scholar]
  48. Kanteh A, Sesay AK, Alikhan N-F, Ikumapayi UN, Salaudeen R et al. Invasive atypical non-typhoidal Salmonella serovars in The Gambia. Microb Genom 2021; 7: [View Article] [PubMed]
    [Google Scholar]
  49. Branchu P, Bawn M, Kingsley RA et al. Genome variation and molecular epidemiology of Salmonella enterica Serovar Typhimurium pathovariants. Infect Immun 2018; 86:1–17 [View Article] [PubMed]
    [Google Scholar]
  50. Panzenhagen PHN, Paul NC, Conte CA, Costa RG, Rodrigues DP et al. Genetically distinct lineages of Salmonella Typhimurium ST313 and ST19 are present in Brazil. Int J Med Microbiol 2018; 308:306–316 [View Article] [PubMed]
    [Google Scholar]
  51. den Bakker HC, Moreno Switt AI, Govoni G, Cummings CA, Ranieri ML et al. Genome sequencing reveals diversification of virulence factor content and possible host adaptation in distinct subpopulations of Salmonella enterica. BMC Genomics 2011; 12:425 [View Article] [PubMed]
    [Google Scholar]
  52. Dione MM, Ikumapayi UN, Saha D, Mohammed NI, Geerts S et al. Clonal differences between Non-Typhoidal Salmonella (NTS) recovered from children and animals living in close contact in the Gambia. PLoS Negl Trop Dis 2011; 5:e1148 [View Article] [PubMed]
    [Google Scholar]
  53. Wilson CN, Pulford CV, Akoko J, Perez Sepulveda B, Predeus AV et al. Salmonella identified in pigs in Kenya and Malawi reveals the potential for zoonotic transmission in emerging pork markets. PLoS Negl Trop Dis 2020; 14:11 [View Article] [PubMed]
    [Google Scholar]
  54. Kotloff KL, Nataro JP, Blackwelder WC, Nasrin D, Farag TH et al. Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study. Lancet 2013; 382:209–222 [View Article] [PubMed]
    [Google Scholar]
  55. Kasumba IN, Pulford CV, Perez-Sepulveda BM, Sen S, Sayed N et al. Characteristics of Salmonella recovered from stools of children enrolled in the global enteric multicenter study. Clin Infect Dis 2021; 73:631–641 [View Article] [PubMed]
    [Google Scholar]
  56. Gordon MA. Invasive nontyphoidal Salmonella disease: epidemiology, pathogenesis and diagnosis. Curr Opin Infect Dis 2011; 24:484–489 [View Article] [PubMed]
    [Google Scholar]
  57. Mackenzie G, Ceesay SJ, Hill PC, Walther M, Bojang KA et al. A decline in the incidence of invasive non-typhoidal Salmonella infection in The Gambia temporally associated with a decline in malaria infection. PLoS One 2010; 5:e10568 [View Article] [PubMed]
    [Google Scholar]
  58. Uche IV, MacLennan CA, Saul A et al. A systematic review of the incidence, risk factors and case fatality rates of invasive nontyphoidal Salmonella (iNTS) disease in Africa (1966 to 2014). PLoS Negl Trop Dis 2017; 11:e0005118 [View Article] [PubMed]
    [Google Scholar]
  59. Molyneux EM, Mankhambo LA, Phiri A, Graham SM, Forsyth H et al. The outcome of non-typhoidal salmonella meningitis in Malawian children, 1997-2006. Ann Trop Paediatr 2009; 29:13–22 [View Article] [PubMed]
    [Google Scholar]
  60. Keddy KH, Sooka A, Musekiwa A, Smith AM, Ismail H et al. Clinical and microbiological features of Salmonella meningitis in a South African population, 2003-2013. Clin Infect Dis 2015; 61 Suppl 4:S272–82 [View Article] [PubMed]
    [Google Scholar]
  61. Zaman SM, Howie SR, Ochoge M, Secka O, Bah A et al. Impact of routine vaccination against Haemophilus influenzae type b in The Gambia: 20 years after its introduction. J Glob Health 2020; 10:010416 [View Article] [PubMed]
    [Google Scholar]
  62. Mackenzie GA, Hill PC, Jeffries DJ, Hossain I, Uchendu U et al. Effect of the introduction of pneumococcal conjugate vaccination on invasive pneumococcal disease in The Gambia: a population-based surveillance study. Lancet Infect Dis 2016; 16:703–711 [View Article] [PubMed]
    [Google Scholar]
  63. Gomes C, Martínez-Puchol S, Palma N, Horna G, Ruiz-Roldán L et al. Macrolide resistance mechanisms in Enterobacteriaceae: Focus on azithromycin. Crit Rev Microbiol 2017; 43:1–30 [View Article] [PubMed]
    [Google Scholar]
  64. Salipante SJ, Hall BG. Determining the limits of the evolutionary potential of an antibiotic resistance gene. Mol Biol Evol 2003; 20:653–659 [View Article] [PubMed]
    [Google Scholar]
  65. Springer B, Kidan YG, Prammananan T, Ellrott K, Böttger EC et al. Mechanisms of streptomycin resistance: selection of mutations in the 16S rRNA gene conferring resistance. Antimicrob Agents Chemother 2001; 45:2877–2884 [View Article] [PubMed]
    [Google Scholar]
  66. Afema JA, Byarugaba DK, Shah DH, Atukwase E, Nambi M et al. Potential sources and transmission of Salmonella and antimicrobial resistance in Kampala, Uganda. PLoS One 2016; 11:e0152130 [View Article] [PubMed]
    [Google Scholar]
  67. Laxminarayan R, Duse A, Wattal C, Zaidi AKM, Wertheim HFL et al. Antibiotic resistance-the need for global solutions. Lancet Infect Dis 2013; 13:1057–1098 [View Article] [PubMed]
    [Google Scholar]
  68. Carroll LM, Wiedmann M, den Bakker H, Siler J, Warchocki S et al. Whole-genome sequencing of drug-resistant Salmonella enterica isolates from dairy cattle and humans in New York and Washington states reveals source and geographic associations. Appl Environ Microbiol 2017; 83:12 [View Article] [PubMed]
    [Google Scholar]
  69. Kariuki S, Oundo JO, Muyodi J, Lowe B, Threlfall EJ et al. Genotypes of multidrug-resistant Salmonella enterica serotype typhimurium from two regions of Kenya. FEMS Immunol Med Microbiol 2000; 29:9–13 [View Article] [PubMed]
    [Google Scholar]
  70. Cheng RA, Eade CR, Wiedmann M et al. Embracing diversity: differences in virulence mechanisms, disease severity, and host adaptations contribute to the success of nontyphoidal Salmonella as a foodborne pathogen. Front Microbiol 2019; 10:10 [View Article] [PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/mgen/10.1099/mgen.0.000785
Loading
/content/journal/mgen/10.1099/mgen.0.000785
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error