Location: Infectious Bacterial Diseases ResearchTitle: Comparative genomics of archived pyrazinamide resistant Mycobacterium tuberculosis complex isolates from Uganda Author
Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 9/27/2016
Publication Date: N/A
Citation: N/A Interpretive Summary:
Technical Abstract: Bovine tuberculosis is a ‘neglected zoonosis’ and its contribution to the proportion of Mycobacterium tuberculosis complex infections in humans is unknown. A retrospective study on archived Mycobacterium tuberculosis complex (MTC) isolates from a reference laboratory in Uganda was undertaken to identify prevalence of human M. bovis infection. Of the 5,676 isolates analyzed, a total of 136 isolates were pyrazinamide resistant. Of these, 1.5% (n = 2) isolates were confirmed and 5 were identified as suspect for M. bovis using regions of difference PCR analysis. The overall size of whole genome sequences (WGS) of the two Ugandan M. bovis isolates were ~ 4.272 Mb (M. bovis Bz 31150 isolated from a captive chimpanzee) and 4.17 Mb (M. bovis B2 7505 from a human patient), respectively. Alignment of these genomes against 17 MTBC genome sequences revealed a total of 7248 SNPs that were used to generate a maximum parsimony tree with 1000 bootstrap replications. Phylogenetic analysis indicated a strong relationship between M. bovis from the chimpanzee (Bz 31150) with other M. bovis genomes analyzed while B2 7505, M. bovis from a human patient, did not cluster with any M. bovis or M. tuberculosis strains suggesting that this strain likely underwent multiple genomic changes to adapt to the human host. WGS analysis also revealed multidrug resistance genotypes; these genomes revealed pncA mutations at positions H57D in Bz 31150 and P54Q mutation in B2 7505. Phenotypically B2 7505 was a multi-drug resistant strain and this was confirmed by the presence of mutations in the major resistant-associated proteins for all anti-TB drugs including isoniazid (KatG (S315T) and InhA (S94A)), and streptomycin (rrs (R309C)). The presence of these mutations exclusively in the human isolate suggest that these occurred after transmission from cattle. Genome analysis in this study identified M. bovis in humans and greater apes suggesting transmission from domesticated ruminants in the area. Future studies included development of an affordable SNP-chip to achieve sensitive, specific and rapid results for MTC detection and typing to enable real time monitoring of interspecies transmission.