Culture-free whole genome sequencing of Mycobacterium tuberculosis using ligand- mediated bead enrichment strategy

Direct whole genome sequencing (WGS) of Mycobacterium tuberculosis (Mtb) can be usedas a tool to study drug resistance, mixed infections, and within host diversity. However, it ischallenging to recover DNA from clinical samples due low bacilli number against highbackground. We used a ligand-mediated magnetic bead method to enrich Mtb from clinicalsamples and performed WGS. Magnetic bead based Mtb enrichment method improved the recovery of Mtb from clinical samples, including smear negative cases, enabling detection of drug resistance, mixed infection, and phylogeny. This approach can be integrated with the low-cost sequencingworkflows for rapid detection of drug resistance and WGS of Mtb.