title: Detection and characterization of drug-resistant conferring genes in Mycobacterium tuberculosis complex strains: A prospective study in two distant regions of Ghana.
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.
authors.affiliation: Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana; Department of Biochemistry, Cell and Molecular Biology, University of Ghana, Accra, Ghana.
authors.forename: I D
authors.initials: ID
authors.lastname: Otchere
authors.affiliation: Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana.
authors.forename: A
authors.initials: A
authors.lastname: Asante-Poku
authors.affiliation: Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana.
authors.forename: S
authors.initials: S
authors.lastname: Osei-Wusu
authors.affiliation: Chest Clinic, Korle-BU Teaching Hospital, Accra, Ghana.
authors.forename: A
authors.initials: A
authors.lastname: Baddoo
authors.affiliation: Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana.
authors.forename: E
authors.initials: E
authors.lastname: Sarpong
authors.affiliation: Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana.
authors.forename: A H
authors.initials: AH
authors.lastname: Ganiyu
authors.affiliation: Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana.
authors.forename: S Y
authors.initials: SY
authors.lastname: Aboagye
authors.affiliation: Chest Clinic, Korle-BU Teaching Hospital, Accra, Ghana.
authors.forename: A
authors.initials: A
authors.lastname: Forson
authors.affiliation: Ghana Health Service, Ministry of Health, Accra, Ghana.
authors.forename: F
authors.initials: F
authors.lastname: Bonsu
authors.affiliation: Chest Department, Tamale Teaching Hospital, Tamale, Ghana.
authors.forename: A I
authors.initials: AI
authors.lastname: Yahayah
authors.affiliation: Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana.
authors.forename: K
authors.initials: K
authors.lastname: Koram
authors.affiliation: Swiss TPH, Basel, Switzerland; University of Basel, Basel, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Gagneux
authors.affiliation: Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana. Electronic address: Dyeboah-Manu@noguchi.ug.edu.gh.
authors.forename: D
authors.initials: D
authors.lastname: Yeboah-Manu
mesh_terms: D000995:Antitubercular Agents / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D005260:Female; D005838:Genotype; D005869:Ghana; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity; D010641:Phenotype; D011446:Prospective Studies; D013183:Sputum / Q000382:microbiology; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis / Q000188:drug therapy / Q000382:microbiology*; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis / Q000188:drug therapy / Q000382:microbiology*; D014774:Virulence
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins
keywords: Compensatory; Drug resistant; Mutations; Spoligotype; Virulence