Analysis of the twenty-six largest outbreaks of tuberculosis in Aragon using whole-genome sequencing for surveillance purposes
Abstract The incidence of tuberculosis in Aragon, Spain, is around ten cases per 100,000 inhabitants. Since 2004, a molecular surveillance protocol has been carried out; therefore, all M. tuberculosis strains are genotyped. Recently, whole-genome sequencing has been implemented for relevant isolates...
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| Format: | Article |
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Nature Portfolio
2022-11-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-23343-1 |
| _version_ | 1811329065396731904 |
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| author | Jessica Comín Alberto Cebollada Daniel Ibarz Jesús Viñuelas Juan Sahagún Luis Torres María-José Iglesias Sofía Samper |
| author_facet | Jessica Comín Alberto Cebollada Daniel Ibarz Jesús Viñuelas Juan Sahagún Luis Torres María-José Iglesias Sofía Samper |
| author_sort | Jessica Comín |
| collection | DOAJ |
| description | Abstract The incidence of tuberculosis in Aragon, Spain, is around ten cases per 100,000 inhabitants. Since 2004, a molecular surveillance protocol has been carried out; therefore, all M. tuberculosis strains are genotyped. Recently, whole-genome sequencing has been implemented for relevant isolates. The aim of this work is to characterise at the molecular level the causative strains of the 26 largest outbreaks of the community (including ten or more cases), genotyped by IS6110-RFLP and causing 26% of tuberculosis cases. To achieve this objective, two or three isolates of each IS6110-cluster belonging to different years were selected for sequencing. We found that strains of lineages L4.8, L4.3 and L4.1.2 were the most frequent. The threshold of 12 SNPs as the maximum distance for confirming the belonging to an outbreak was met for 18 of the 26 IS6110-clusters. Four pairs of isolates with more than 90 SNPs were identified as not belonging to the same strain, and four other pairs were kept in doubt as the number of SNPs was close to 12, between 14 and 35. The study of Regions of Difference revealed that they are lineage conserved. Moreover, we could analyse the IS6110 locations for all genome-sequenced isolates, finding some frequent locations in isolates belonging to the same lineage and certain IS6110 movements between the paired isolates. In the vast majority, these movements were not captured by the IS6110-RFLP pattern. After classifying the genes containing SNP by their functional category, we could confirm that the number of SNPs detected in genes considered as virulence factors and the number of cases the strain produced were not related, suggesting that a particular SNP is more relevant than the number. The characteristics found in the most successful strains in our community could be useful for other researchers in epidemiology, virulence and pathogenesis. |
| first_indexed | 2024-04-13T15:37:13Z |
| format | Article |
| id | doaj.art-0fa328b4f6cd4d738c9e3497a56acbc1 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-13T15:37:13Z |
| publishDate | 2022-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-0fa328b4f6cd4d738c9e3497a56acbc12022-12-22T02:41:14ZengNature PortfolioScientific Reports2045-23222022-11-0112111010.1038/s41598-022-23343-1Analysis of the twenty-six largest outbreaks of tuberculosis in Aragon using whole-genome sequencing for surveillance purposesJessica Comín0Alberto Cebollada1Daniel Ibarz2Jesús Viñuelas3Juan Sahagún4Luis Torres5María-José Iglesias6Sofía Samper7Instituto Aragonés de Ciencias de la SaludInstituto Aragonés de Ciencias de la SaludUniversidad de ZaragozaHospital Universitario Miguel ServetHospital Clínico Universitario Lozano BlesaHospital San JorgeUniversidad de ZaragozaInstituto Aragonés de Ciencias de la SaludAbstract The incidence of tuberculosis in Aragon, Spain, is around ten cases per 100,000 inhabitants. Since 2004, a molecular surveillance protocol has been carried out; therefore, all M. tuberculosis strains are genotyped. Recently, whole-genome sequencing has been implemented for relevant isolates. The aim of this work is to characterise at the molecular level the causative strains of the 26 largest outbreaks of the community (including ten or more cases), genotyped by IS6110-RFLP and causing 26% of tuberculosis cases. To achieve this objective, two or three isolates of each IS6110-cluster belonging to different years were selected for sequencing. We found that strains of lineages L4.8, L4.3 and L4.1.2 were the most frequent. The threshold of 12 SNPs as the maximum distance for confirming the belonging to an outbreak was met for 18 of the 26 IS6110-clusters. Four pairs of isolates with more than 90 SNPs were identified as not belonging to the same strain, and four other pairs were kept in doubt as the number of SNPs was close to 12, between 14 and 35. The study of Regions of Difference revealed that they are lineage conserved. Moreover, we could analyse the IS6110 locations for all genome-sequenced isolates, finding some frequent locations in isolates belonging to the same lineage and certain IS6110 movements between the paired isolates. In the vast majority, these movements were not captured by the IS6110-RFLP pattern. After classifying the genes containing SNP by their functional category, we could confirm that the number of SNPs detected in genes considered as virulence factors and the number of cases the strain produced were not related, suggesting that a particular SNP is more relevant than the number. The characteristics found in the most successful strains in our community could be useful for other researchers in epidemiology, virulence and pathogenesis.https://doi.org/10.1038/s41598-022-23343-1 |
| spellingShingle | Jessica Comín Alberto Cebollada Daniel Ibarz Jesús Viñuelas Juan Sahagún Luis Torres María-José Iglesias Sofía Samper Analysis of the twenty-six largest outbreaks of tuberculosis in Aragon using whole-genome sequencing for surveillance purposes Scientific Reports |
| title | Analysis of the twenty-six largest outbreaks of tuberculosis in Aragon using whole-genome sequencing for surveillance purposes |
| title_full | Analysis of the twenty-six largest outbreaks of tuberculosis in Aragon using whole-genome sequencing for surveillance purposes |
| title_fullStr | Analysis of the twenty-six largest outbreaks of tuberculosis in Aragon using whole-genome sequencing for surveillance purposes |
| title_full_unstemmed | Analysis of the twenty-six largest outbreaks of tuberculosis in Aragon using whole-genome sequencing for surveillance purposes |
| title_short | Analysis of the twenty-six largest outbreaks of tuberculosis in Aragon using whole-genome sequencing for surveillance purposes |
| title_sort | analysis of the twenty six largest outbreaks of tuberculosis in aragon using whole genome sequencing for surveillance purposes |
| url | https://doi.org/10.1038/s41598-022-23343-1 |
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