High-throughput phenogenotyping of Mycobacteria tuberculosis clinical strains reveals bacterial determinants of treatment outcomes

We developed a high-throughput functional genomics platform for defining genotype-phenotype
relationships across a panel of Mtb clinical isolates. These phenotypic fitness profiles function
as intermediate traits which can be linked to Mtb genetic variants and associated with clinical
and epidemiological outcomes. We applied this approach to a collection of 158 Mtb strains from
a study of Mtb transmission in Ho Chi Minh City, Vietnam. Mtb strains were genetically tagged
in multiplicate, which allowed us to pool the strains and assess in vitro competitive fitness using
deep sequencing across a set of 14 host-relevant antibiotic and metabolic conditions.
Phylogenetic and monogenic associations with these intermediate traits were identified and then
associated with clinical outcomes.

[ Download ]