Perceived ethionamide resistance in isoniazid susceptible isolates of mycobacterium tuberculosis.
Loading...
Date
2015
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
In Mycobacterium tuberculosis, resistance to ethionamide (ETH) is usually combined with
isoniazid (INH) resistance due to a number of mutations in genes that are involved in the
biosynthesis of mycolic acids. ETH resistance in INH susceptible isolates is rare. Ten such
isolates were identified from patients participating in other studies.
Genotyping by means of IS6110 was performed to compare the relatedness of these isolates
to each other. In attempts to identify the molecular basis for the resistance to ETH, the ethA,
mshA and mshC genes were amplified and the amplicons sequenced using an ABI 3730 DNA
Analyser. INH and ETH minimum inhibitory concentrations (MICs) were determined alone
and in combination by means of checkerboard titrations in Middlebrook 7H9 broth, using the
3-(4,5-dimethylthiozol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and microplate
alamarblue assays (MABA) for detection of growth.
Seven isolates were not related to each other and their INH susceptibility was confirmed. No
mutations were observed in all the sequenced genes. One out of seven isolates was found to
be co-resistant to INH nad ETH. The MIC for the remaining isolates was 1μg/ml for ETH.
MABA revealed a paradoxical susceptibility of the isolates to ETH, where mycobacterial
growth was observed in ETH concentrations higher than the MIC for the six isolates. For
combination of the two drugs, MABA revealed an antagonism between INH and ETH, where
the isolates grew in high ETH concentrations regardless of the concentration of INH.
The paradoxical effect of ETH and antagonism between ETH and INH in our isolates does
not result from mutations in ethA, mshA or mshC.
Description
M. Med. Sc. University of KwaZulu-Natal, Durban 2015.
Keywords
Mycobacterium tuberculosis., Isoniazid., Theses--Medical microbiology.