P62
Whole Genome Analysis of Mycobacterium tuberculosis samples in Georgia
M R Galac(1) B Jeffrey(1) I Khurtsilava(2) M Shurgaia(2) M Harris(1) S Vashakidze(2,3) N Shubladze(2)
1:Office of Cyber Infrastructure & Computational Biology, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland, USA; 2:National Center for Tuberculosis and Lung Diseases of Georgia, Tbilisi, Georgia; 3:The University of Georgia, Tbilisi, Georgia
The whole genome sequences of 1184 Mycobacterium tuberculosis isolates from the country of Georgia were analyzed as part of the TB Portals collection. Georgia is known to have a heavy burden of drug resistant TB. These samples were mainly collected from patient sputum and belonged to either Beijing (lineage 2) or Euro-American (lineage 4) lineages, though 2 samples from separate patients are CAS lineage (lineage 3). Drug resistance (DR) status of these samples was predicted based on single nucleotide polymorphisms (SNPs) to range from no DR (n=490), mono-DR (n=103), other DR (n=91), MDR (n=350), pre-XDR (n=259) to XDR (n=3, all Beijing lineage). Whole-genome SNP phylogenic data revealed multiple close clades of samples within the Beijing lineage predicted to be either MDR or pre-XDR. A network analysis was used to determine that there are both cases where pre-XDR was arising independently and where they were spreading. The three XDR samples are not clonal and the transition from pre-XDR to XDR happened independently each time. One sample acquired an SNP in rplC (Cys154Arg) predicted to confer linezolid resistance while the other two have the same SNP in mmpR5 (198dupG) which would provide resistance to bedaquiline. Network analysis was used to determine that the two bedaquiline resistant XDR samples acquired the SNP independently. Based on this collection of samples, DR TB prevalence in Georgia is the result of both isolates acquiring new SNPs providing DR and samples that already have DR spreading to new patients.