Dataset Information

Whole genome sequencing of multidrug-resistant Mycobacterium tuberculosis isolates collected in the Czech Republic, 2005-2020.

ABSTRACT: The emergence and spread of resistant tuberculosis (TB) pose a threat to public health, so it is necessary to diagnose the drug-resistant forms in a clinically short time frame and closely monitor their transmission. In this study, we carried out a first whole genome sequencing (WGS)-based analysis of multidrug resistant (MDR) M. tuberculosis strains to explore the phylogenetic lineages diversity, drug resistance mechanisms, and ongoing transmission chains within the country. In total, 65 isolates phenotypically resistant to at least rifampicin and isoniazid collected in the Czech Republic in 2005-2020 were enrolled for further analysis. The agreement of the results obtained by WGS with phenotypic drug susceptibility testing (pDST) in the determination of resistance to isoniazid, rifampicin, pyrazinamide, streptomycin, second-line injectables and fluoroquinolones was more than 80%. Phylogenetic analysis of WGS data revealed that the majority of MDR M. tuberculosis isolates were the Beijing lineage 2.2.1 (n = 46/65; 70.8%), while the remaining strains belonged to Euro-American lineage. Cluster analysis with a predefined cut-off distance of less than 12 single nucleotide polymorphisms between isolates showed 19 isolates in 6 clusters (clustering rate 29.2%), located mainly in the region of the capital city of Prague. This study highlights the utility of WGS as a high-resolution approach in the diagnosis, characterization of resistance patterns, and molecular-epidemiological analysis of resistant TB in the country.

SUBMITTER: Dohal M

PROVIDER: S-EPMC9062869 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Whole genome sequencing of multidrug-resistant Mycobacterium tuberculosis isolates collected in the Czech Republic, 2005-2020.

Dohál Matúš M Dvořáková Věra V Šperková Miluše M Pinková Martina M Spitaleri Andrea A Norman Anders A Cabibbe Andrea Maurizio AM Rasmussen Erik Michael EM Porvazník Igor I Škereňová Mária M Solovič Ivan I Cirillo Daniela Maria DM Mokrý Juraj J

Scientific reports 20220503 1

The emergence and spread of resistant tuberculosis (TB) pose a threat to public health, so it is necessary to diagnose the drug-resistant forms in a clinically short time frame and closely monitor their transmission. In this study, we carried out a first whole genome sequencing (WGS)-based analysis of multidrug resistant (MDR) M. tuberculosis strains to explore the phylogenetic lineages diversity, drug resistance mechanisms, and ongoing transmission chains within the country. In total, 65 isolat ...[more]

PMID: 35505072

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Project description:Invasive meningococcal disease belongs among the most dangerous infectious diseases in the world. Several polysaccharide conjugate vaccines against serogroups A, C, W and Y are available and two recombinant peptide vaccines against serogroup B (MenB vaccines) have been developed: MenB-4C (Bexsero) and MenB-fHbp (Trumenba). The aim of this study was to define the clonal composition of the Neisseria meningitidis population in the Czech Republic, to determine changes in this population over time and to estimate the theoretical coverage of isolates by MenB vaccines. This study presents the analysis of whole genome sequencing data of 369 Czech N. meningitidis isolates from invasive meningococcal disease covering 28 years. Serogroup B isolates (MenB) showed high heterogeneity and the most common clonal complexes were cc18, cc32, cc35, cc41/44, and cc269. Isolates of clonal complex cc11 were predominately serogroup C (MenC). The highest number of serogroup W isolates (MenW) belonged to clonal complex cc865, which we described as exclusive to the Czech Republic. Our study supports the theory that this cc865 subpopulation originated in the Czech Republic from MenB isolates by a capsule switching mechanism. A dominant clonal complex of serogroup Y isolates (MenY) was cc23, which formed two genetically quite distant subpopulations and which showed constant representation throughout the observed period. The theoretical coverage of isolates by two MenB vaccines was determined using the Meningococcal Deduced Vaccine Antigen Reactivity Index (MenDeVAR). Estimated Bexsero vaccine coverage was 70.6% (for MenB) and 62.2% (for MenC, W, Y). For Trumenba vaccine, estimated coverage was 74.6% (for MenB) and 65.7% (for MenC, W, Y). Our results demonstrated sufficient coverage of Czech heterogeneous population of N. meningitidis with MenB vaccines and, together with surveillance data on invasive meningococcal disease in the Czech Republic, were the basis for updating recommendations for vaccination against invasive meningococcal disease.

Project description:IntroductionThe study presents the analysis of whole genome sequencing (WGS) data for Neisseria meningitidis serogroup Y isolates collected in the Czech Republic and their comparison to other countries. The aim of the study was to determine whether there are lineages of N. meningitidis serogroup Y in the Czech Republic genetically related to foreign ones that have been causing an increase of the morbidity and the mortality of invasive meningococcal disease (IMD) world-wide recently.Material and methodsThe WGS data of 43 Czech N. meningitidis Y isolates, 35 from IMD and 8 from healthy carriers were analysed. Due to the potential of meningococcal B vaccines to induce protection against non-B serogroups, the coverage of Czech isolates of N. meningitidis Y by these vaccines was studied. The WGS data of Czech, European and non-European isolates of N. meningitidis serogroup Y were compared.ResultsWGS assigned 36 isolates of N. meningitidis Y to five clonal complexes: cc23, cc92, cc167, cc103, and cc174, while seven isolates remained unassigned to any clonal complexes (ccUA). Eighteen invasive isolates belonged to clonal complex cc23, which was detected throughout the studied years. The occurrence of cc23 was recorded in all age groups of IMD patients, with the highest found in those aged 15-19 years. On the phylogenetic network isolates of cc23 form a separate lineage, distinct from all other isolates of N. meningitidis Y. The remaining isolates were assigned to other clonal complexes and have very low relatedness to cc23 isolates and to each other. The comparison with foreign WGS data showed that within the main genetic lineages, which are defined by clonal complexes, Czech isolates of N. meningitidis Y, similar to European ones, mostly cluster together and form geographical sublineages.ConclusionsWGS analysis showed the population of Czech N. meningitidis Y isolates as relatively heterogeneous, containing a large number of genetic lineages. The Czech isolates of N. meningitidis Y follow the trend observed for European isolates. Our result was one of the bases for updating the recommended vaccination strategy in the Czech Republic.

Project description:IntroductionThe study presents the analysis of whole genome sequence (WGS) data for Neisseria meningitidis serogroup W isolates recovered in the Czech Republic in 1984-2017 and their comparison with WGS data from other countries.Material and methodsThirty-one Czech N. meningitidis W isolates, 22 from invasive meningococcal disease (IMD) and nine from healthy carriers were analysed. The 33-year study period was divided into three periods: 1984-1999, 2000-2009, and 2010-2017.ResultsMost study isolates from IMD and healthy carriers were assigned to clonal complex cc22 (n = 10) in all study periods. The second leading clonal complex was cc865 (n = 8) presented by IMD (n = 7) and carriage (n = 1) isolates that emerged in the last study period, 2010-2017. The third clonal complex was cc11 (n = 4) including IMD isolates from the first (1984-1999) and third (2010-2017) study periods. The following clonal complex was cc174 (n = 3) presented by IMD isolates from the first two study periods, i.e. 1984-1999 and 2000-2009. One isolate of each cc41/44 and cc1136 originated from healthy carriers from the second study period, 2000-2009. The comparison of WGS data for N. meningitidis W isolates recovered in the Czech Republic in the study period 1984-2017 and for isolates from other countries recovered in the same period showed that clonal complex cc865, ST-3342 is unique to the Czech Republic since 2010. Moreover, the comparison shows that cc11 in the Czech Republic does not comprise novel hypervirulent lineages reported from both European and non-European countries. All 31 study isolates were assigned to Bexsero® Antigen Sequence Types (BAST), and seven of them were of newly described BASTs.ConclusionsWGS analysis contributed considerably to a more detailed molecular characterization of N. meningitidis W isolates recovered in the Czech Republic over a 33-year period and allowed for a spatial and temporal comparison of these characteristics between isolates from the Czech Republic and other countries. The most interesting finding of this study is that eight of 31 Czech isolates of N. meningitidis W belong to clonal complex cc865, which is uncommon for serogroup W. In addition, the WGS data precised the base for the update of the recommendation for vaccination in the Czech Republic.

Dataset Information

Whole genome sequencing of multidrug-resistant Mycobacterium tuberculosis isolates collected in the Czech Republic, 2005-2020.

Publications

Whole genome sequencing of multidrug-resistant Mycobacterium tuberculosis isolates collected in the Czech Republic, 2005-2020.

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