WHO: Public call for whole genome sequencing and phenotypic data from clinical isolates of M. tuberculosis complex

Following the publication in 2021 of the Catalogue of mutations in Mycobacterium tuberculosis complex and their association with drug resistance, which provides a reference standard for the interpretation of mutations conferring resistance to all first-line and a variety of second-line drugs, the World Health Organization (WHO) is now in the process of updating the catalogue to accommodate additional evidence of resistance linked to genotype.

While almost 40,000 Mycobacterium tuberculosis complex (MTBC) isolates from a large number of countries were analyzed for the 2021 catalogue, the number of isolates with phenotypic resistance to the newly endorsed or repurposed therapeutics (e.g. bedaquiline, delamanid, and linezolid) was limited.

The main focus of the update will be to collect, collate and analyze genotypic and phenotypic data with known resistance to new and repurposed TB therapeutics, as well as to expand coverage of data to countries not yet represented in the catalogue.

To ensure inclusion of all available data by mid-2022, WHO is issuing a public call, appealing to national TB programmes, public health bodies, industry, researchers and other agencies to provide suitable datasets.

The following essential criteria are required for inclusion of data:

• Datasets of unique, clinical MTBC isolates phenotypically either susceptible or resistant to bedaquiline, clofazimine, delamanid and linezolid or with mutations in key genes associated with resistance to these drugs regardless of phenotype result.
• Whole genome squencing or targeted amplicon sequencing performed using either Illumina or Oxford Nanopore technology (raw fastq files preferred over filtered/decontaminated fastq files).
• Drug susceptibility testing (DST) performed using WHO recommended methods and critical concentrations (either on solid or liquid media), or with minimum inhibitory concentration estimates. DST data performed on broth micro-dilution methods will also be considered.
• DST data should be organized in anonymized, individual records (i.e. one row per clinical isolate). See Annex 1 for a possible template for submission.

Other criteria relevant for inclusion are:

• Any MTBC sequencing/phenotypic datasets (WHO recommended DST) from countries and regions not represented or underrepresented in the current collection (see Annex 2 for list of countries represented in the present catalogue).
• Sequencing/phenotypic datasets including M. africanum strains.
• Phenotypically resistant strains to bedaquiline, clofazimine, delamanid and linezolid without  sequencing data or performed on alternative sequencing platforms may be considered for further characterization and inclusion.

Please let us know by 31 May 2022 if you have data to contribute, by sending an email to Carl- Michael Nathanson at the Global TB Programme, WHO, [email protected], with the subject line ‘’TB mutation catalogue’’. 

Related links:

Annex 1

Annex 2

Source: World Health Organization