Characterization of Large Deletion Mutants of Mycobacterium tuberculosis Selected for Isoniazid Resistance
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Authors: Vilcheze, Catherine; Saranathan, Rajagopalan; Weinrick, Brian; Jacobs, William R., Jr.
Abstract
Large genomic deletions (LGDs) (6 to 63 kbp) were observed in isoniazid-resistant Mycobacterium tuberculosis mutants derived from four M. tuberculosis strains. These LGDs had no growth defect in vitro but could be defective in intracellular growth and showed various sensitivities toward oxidative stress despite lacking katG. The LGD regions comprise 74 genes, mostly of unknown function, that may be important for M. tuberculosis intracellular growth and protection against oxidative stress.
Phylogenetic diversity of Mycobacterium tuberculosis in two geographically distinct locations in Botswana - The Kopanyo Study
INFECTION GENETICS AND EVOLUTION
Authors: Click, Eleanor S.; Finlay, Alyssa; Oeltmann, John E.; Basotli, Joyce; Modongo, Chawangwa; Boyd, Rosanna; Wen, Xiao Jun; Shepherd, James; Moonan, Patrick K.; Zetola, Nicola M.
Abstract
Mycobacterium tuberculosis complex (MTBC) is divided into several major phylogenetic lineages, with differential distribution globally. Using population-based data collected over a three year period, we performed 24-locus Mycobacterial Interspersed Repeat Unit - Variable Number Tandem Repeat (MIRU-VNTR) genotyping on all culture isolates from two districts of the country that differ in tuberculosis (TB) incidence (Gaborone, the capital, and Ghanzi in the Western Kalahari). The study objective was to characterize the molecular epidemiology of TB in these districts. Overall phylogenetic diversity mirrored that reported from neighboring Republic of South Africa, but differences in the two districts were marked. All four major lineages of M. tuberculosis were found in Gaborone, but only three of the four major lineages were found in Ghanzi. Strain diversity was lower in Ghanzi, with a large proportion (38%) of all isolates having an identical MIRU-VNTR result, compared to 6% of all isolates in Gaborone with the same MIRU-VNTR result. This study demonstrates localized differences in strain diversity by two districts in Botswana, and contributes to a growing characterization of MTBC diversity globally.