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Detection and characterization of drug-resistant conferring genes in Mycobacterium tuberculosis complex strains : a prospective study in two distant regions of Ghana

Otchere, I. D. and Asante-Poku, A. and Osei-Wusu, S. and Baddoo, A. and Sarpong, E. and Ganiyu, A. H. and Aboagye, S. Y. and Forson, A. and Bonsu, F. and Yahayah, A. I. and Koram, K. and Gagneux, S. and Yeboah-Manu, D.. (2016) Detection and characterization of drug-resistant conferring genes in Mycobacterium tuberculosis complex strains : a prospective study in two distant regions of Ghana. Tuberculosis, 99. pp. 147-154.

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Official URL: http://edoc.unibas.ch/44582/

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Abstract

We spoligotyped and screened 1490 clinical Mycobacterium tuberculosis complex strains from Northern and Greater Accra regions of Ghana against INH and RIF using the microplate alamar blue phenotypic assay. Specific drug resistance associated genetic elements of drug resistant strains were analyzed for mutations. A total of 111 (7.5%), 10 (0.7%) and 40 (2.6%) were mono-resistant to INH, RIF, and MDR, respectively. We found the Ghana spoligotype to be associated with drug resistance (INH: 22.1%; p = 0.0000, RIF: 6.2%; p = 0.0103, MDR: 4.6%; p = 0.0240) as compared to the Cameroon spoligotype (INH: 6.7%, RIF: 2.4%, MDR: 1.6%). The propensity for an isolate to harbour katG S315T mutation was higher in M. tuberculosis (75.8%) than Mycobacterium africanum (51.7%) (p = 0.0000) whereas the opposite was true for inhApro mutations; MAF (48.3%) compared to MTBSS (26.7%) (p = 0.0419). We identified possible novel compensatory INH resistance mutations in inhA (G204D) and ahpCpro (-88G/A and -142G/A) and a novel ndh mutation K32R. We detected two possible rpoC mutations (G332R and V483G), which occurred independently with rpoB S450L, respectively. The study provides the first evidence that associate the Ghana spoligotype with DR-TB and calls for further genome analyses for proper classification of this spoligotype and to explore for fitness implications and mechanisms underlying this observation.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology > Tuberculosis Research (Gagneux)
UniBasel Contributors:Gagneux, Sebastien
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Elsevier
ISSN:1472-9792
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:12 Dec 2016 14:30
Deposited On:12 Dec 2016 14:30

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