Molecular analysis of genetic mutations among cross-resistant second-line injectable drugs reveals a new resistant mutation in Mycobacterium tuberculosis

Malinga, Lesibana Anthony; Brand, Jeannette; Olorunju, Steve; Stoltz, Anton Carel; Van der Walt, Martie

dc.contributor.author	Malinga, Lesibana Anthony
dc.contributor.author	Brand, Jeannette
dc.contributor.author	Olorunju, Steve
dc.contributor.author	Stoltz, Anton Carel
dc.contributor.author	Van der Walt, Martie
dc.date.accessioned	2016-09-05T12:56:23Z
dc.date.available	2016-09-05T12:56:23Z
dc.date.issued	2016-08
dc.description.abstract	Mutations causing mono and cross-resistance among amikacin, kanamycin and capreomycin of second-line injectable drugs (SLIDs) namely are not well understood.We investigated 124 isolates of Mycobacterium tuberculosis for mutations within rrs, eis, tlyA and efflux pump (Rv1258c and Rv0194) genes involved in resistance towards SLIDs. The distribution of mutations across these genes were significantly different in strains with mono-resistance or cross-resistance. A new mutation G878A was found in rrs gene, among strains with capreomycin mono-resistant, or in strains with cross-resistance of capreomycin, kanamycin and amikacin. This mutation was associated with the Euro-American X3 lineage (P b 0.0001). Mutations in the two efflux genes Rv1258c and Rv0194 were confined to strains with only capreomycin/amikacin/kanamycin cross-resistance. Wefurther investigated the minimuminhibitory concentration of capreomycin on isolateswith newG878Amutation ranging from 8 μg/mL to 64 μg/mL. Inclusion of G878A on new molecular assays could increase the sensitivity of capreomycin resistance detection.	en_ZA
dc.description.department	Internal Medicine	en_ZA
dc.description.librarian	hb2016	en_ZA
dc.description.sponsorship	Lesibana Malinga received PhD funding from National Research foundation (Innovation Fund) and University of Pretoria.	en_ZA
dc.description.uri	http://www.elsevier.com/locate/diagmicrobio	en_ZA
dc.identifier.citation	Malinga, L, Brand, J, Olorunju, S, Stoltz, A & Van der Walt, M 2016, 'Molecular analysis of genetic mutations among cross-resistant second-line injectable drugs reveals a new resistant mutation in Mycobacterium tuberculosis', Diagnostic Microbiology and Infectious Disease, vol. 85, no. 4, pp. 433-437.	en_ZA
dc.identifier.issn	0732-8893 (print)
dc.identifier.issn	1879-0070 (online)
dc.identifier.other	10.1016/j.diagmicrobio.2016.05.010
dc.identifier.uri	http://hdl.handle.net/2263/56607
dc.language.iso	en	en_ZA
dc.publisher	Elsevier	en_ZA
dc.rights	© 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).	en_ZA
dc.subject	rrs Gene	en_ZA
dc.subject	G878A mutation	en_ZA
dc.subject	Cross-resistance	en_ZA
dc.subject	Second-line injectable drugs (SLIDs)	en_ZA
dc.subject	Mycobacterium tuberculosis (MTB)	en_ZA
dc.title	Molecular analysis of genetic mutations among cross-resistant second-line injectable drugs reveals a new resistant mutation in Mycobacterium tuberculosis	en_ZA
dc.type	Article	en_ZA