Browsing by Author "Kubica, T."
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Item Pulmonary tuberculosis: virulence of Mycobacterium africanum and relevance in HIV co-infection(Elsevier, 2008) Meyer, C.G.; Scarisbrick, G.; Niemann, S.; Browne, E.N.L.; Chinbuah, M.A.; Gyapong, J.O.; Osei, I.; Owusu-Dabo, E.; Kubica, T.; Rüsch-Gerdes, S.; Thye, T.; Horstmann, R.D.Although Mycobacterium africanum is being isolated in a significant proportion of cases of pulmonary tuberculosis in West Africa, its pathogenic potential remains a matter of discussion. Recent reports leave the question of whether M. africanum causes more severe pathology than M. tuberculosis or resembles opportunistic pathogens and might gain importance in the course of the HIV pandemic. Patients with pulmonary tuberculosis associated with M. africanum(nZ556) and M. tuberculosis (nZ1350) were studied in Ghana, West Africa, and compared regarding self-reported signs and symptoms, chest radiography, HIV status, mycobacterial drug resistance and mycobacterial clustering as determined by spoligotyping and IS6110 fingerprints. The rate of M. africanum infections was similar in HIV-positive (27%) and HIV-negative (30%) patients. M. africanum clustered less than M. tuberculosis (21% vs 79%; OR, 0.38; 95% CI, 0.3e0.5; p < 0.001) corresponding to its lower prevalence (29% vs 70%). Clinically and radiographically, no significant differences were found except that M. africanum caused lower-lobe disease less frequently than M. tuberculosis (OR, 0.39; 95% CI, 0.2e0.7; pcZ0.01), whereby this association applied to HIV-negative patients only. No difference in virulence, as assessed by the severity of radiological presentation, was found when the two M. africanum subtypes West African 1 andWest African 2 were compared. In the population studied, M. africanum closely resembled M. tuberculosis in pathology and cannot be considered an opportunistic pathogen.Item The species Mycobacterium africanum in the light of new molecular markers(2004-09) Niemann, S.; Kubica, T.; Bange, F.C.; Adjei, O.; Browne, E.N.; Chinbuah, M.A.; Diel, R.; Gyapong, J.; Horstmann, R.D.; Joloba, M.L.; Meyer, C.G.; Mugerwa, R.D.; Okwera, A.; Osei, I.; Owusu-Darbo, E.; Schwander, S.K.; Rüsch-Gerdes, S.The findings of recent studies addressing the molecular characteristics of Mycobacterium tuberculosis complex isolates have initiated a discussion on the classification of M. africanum, especially of those isolates originating from East Africa (cluster F, subtype II) and displaying phenotypic and biochemical characteristics more similar to those of M. tuberculosis. To further address this question, we analyzed a representative collection of 63 M. tuberculosis complex strains comprising 30 M. africanum subtype I strains, 20 M. africanum subtype II strains, 10 randomly chosen M. tuberculosis isolates, and type strains of M. tuberculosis, M. bovis, and M. africanum for the following biochemical and molecular characteristics: single-nucleotide polymorphisms (SNPs) in gyrB and narGHJI and the presence or absence of RD1, RD9, and RD12. For all molecular markers analyzed, subtype II strains were identical to the M. tuberculosis strains tested. In contrast, the subtype I strains as well as the M. africanum type strain showed unique combinations of SNPs in gyrB and genomic deletions (the absence of RD9 and the presence of RD12), which proves their independence from M. tuberculosis and M. bovis. Accordingly, all subtype I strains displayed main biochemical characteristics included in the original species description M. africanum. We conclude that the isolates from West Africa were proved to be M. africanum with respect to the phenotypic and genetic markers analyzed, while the isolates from East Africa must be regarded as phenotypic variants of M. tuberculosis (genotype Uganda). We propose the addition of the molecular characteristics defined here to the species description of M. africanum, which will allow clearer species differentiation in the future.Item Unequal distribution of resistance-conferring mutations among Mycobacterium tuberculosis and Mycobacterium africanum strains from Ghana(2010-11) Homolka, S.; Meyer, C.G.; Hillemann, D.; Owusu-Dabo, E.; Adjei, O.; Horstmann, R.D.; Browne, E.N.L.; Chinbuah, A.; Osei, I.; Gyapong, J.; Kubica, T.; Ruesch-Gerdes, S.; Niemann, S.Isoniazid (INH) and rifampicin (RMP) resistance in Mycobacterium tuberculosis complex (MTC) isolates are mainly based on mutations in a limited number of genes. However, mutation frequencies vary in different mycobacterial populations. In this work, we analyzed the distribution of resistance-associated mutations in M. tuberculosis and M. africanum strains from Ghana, West Africa. The distribution of mutations in katG, fabG1-inhA, ahpC, and rpoB was determined by DNA sequencing in 217 INH-resistant (INH r) and 45 multidrug-resistant (MDR) MTC strains isolated in Ghana from 2001 to 2004. A total of 247 out of 262 strains investigated (94.3%) carried a mutation in katG (72.5%), fabG1-inhA (25.1%), or ahpC (6.5%), respectively. M. tuberculosis strains mainly had katG 315 mutations (80.1%), whereas this proportion was significantly lower in M. africanum West-African 1 (WA1) strains (43.1%; p<0.05). In contrast, WA1 strains showed more mutations in the fabG1-inhA region (39.2%, p<0.05) compared to M. tuberculosis strains (20.9%). In 44 of 45 MDR strains (97.8%) mutations in the 81-bp core region of the rpoB gene could be verified. Additionally, DNA sequencing revealed that 5 RMP-susceptible strains also showed mutations in the rpoB hotspot region. In conclusion, although principally the same genes were affected in INH r M. tuberculosis and M. africanum strains, disequilibrium in the distribution of mutations conferring resistance was verified that might influence the efficiency of molecular tests for determination of resistance.