Research Articles

Permanent URI for this communityhttp://197.255.125.131:4000/handle/123456789/22010

A research article reports the results of original research, assesses its contribution to the body of knowledge in a given area, and is published in a peer-reviewed scholarly journal. The faculty publications through published and on-going articles/researches are captured in this community

Browse

Search Results

Now showing 1 - 10 of 10
  • Thumbnail Image
    Item
    Commemorating World TB Day 2020: “IT’S TIME” — It’s time to End the Global TB Epidemic
    (Elsevier Ltd, 2020) Tiberi, S.; Yeboah-Manu, D.; et al.
  • Item
    Relevance of genomic diversity of Mycobacterium tuberculosis complex in Africa
    (Elsevier, 2022) Osei-Wusu, S.; Otchere, I.D.; Asare, P.; Ntoumi, F.; Zumla, A.; Asante-Poku, A.; Yeboah-Manu, D.
    Background: The diversity in the lineages of Mycobacterium tuberculosis complex (MTBC) was initially considered insignificant. However, comparative genomics analysis of MTBC have found genomic variation among the genotypes with potential phenotypic implications. Objective: Therefore, this viewpoint seeks to discuss the impact of the identified genotypic diversity on the physiology of MTBC and the potential implications on TB control. Results: Studies conducted in West Africa and other parts of Africa have unravelled the implications of the genomic diversity on phenotypes such as disease outcome, transmission dynamics and host immune response. The understanding of the phenotypic diversity among the different lineages of MTBC may be an important key to the fight against TB. Conclusion: The relevance of these differences has been observed in the design of new control tools such as diagnostics and anti-TB drugs/vaccines. This only points to the fact that the diversity in MTBC cannot be ignored in future studies especially clinical trials for new vaccines and new anti-TB drugs.
  • Thumbnail Image
    Item
    Local adaptation in populations of Mycobacterium tuberculosis endemic to the Indian Ocean Rim[version 1; peer review: 3 approved]
    (F1000Research, 2021) Menardo, F.; Rutaihwa, L.K.; Zwyer, M.; Borrell, S.; Comas, I.; Conceição, E.C.; Coscolla, M.; Cox, H.; Joloba, M.; Dou, H.; Feldmann, J.; Fenner, L.; Fyfe, J.; Gao, Q.; de Viedma, D.G.; Garcia-Basteiro, A.L.; Gygli, S.M.; Hella, J.; Hiza, H.; Jugheli, L.; Kamwela, L.; Kato-Maeda, M.; Liu, Q.; Ley, S.D.; Loiseau, C.; Mahasirimongkol, S.; Malla, B.; Palittapongarnpim, P.; Rakotosamimanana, N.; Rasolofo, V.; Reinhard, M.; Reither, K.; Sasamalo, M.; Duarte, R.S.; Sola, C.; Suffys, P.; Lima, K.V.B.; Yeboah-Manu, D.; Beisel, C.; Brites, D.; Gagneux, S.
    Background: Lineage 1 (L1) and 3 (L3) are two lineages of the Mycobacterium tuberculosis complex (MTBC) causing tuberculosis (TB) in humans. L1 and L3 are prevalent around the rim of the Indian Ocean, the region that accounts for most of the world’s new TB cases. Despite their relevance for this region, L1 and L3 remain understudied. Methods: We analyzed 2,938 L1 and 2,030 L3 whole genome sequences originating from 69 countries. We reconstructed the evolutionary history of these two lineages and identified genes under positive selection. Results: We found a strongly asymmetric pattern of migration from South Asia toward neighboring regions, highlighting the historical role of South Asia in the dispersion of L1 and L3. Moreover, we found that several genes were under positive selection, including genes involved in virulence and resistance to antibiotics . For L1 we identified signatures of local adaptation at the esxH locus, a gene coding for a secreted effector that targets the human endosomal sorting complex, and is included in several vaccine candidates. Conclusions: Our study highlights the importance of genetic diversity in the MTBC, and sheds new light on two of the most important MTBC lineages affecting humans.
  • Thumbnail Image
    Item
    Genotypic and phenotypic diversity of Mycobacterium tuberculosis complex genotypes prevalent in West Africa
    (PLOS ONE, 2021) Osei-Wusu, S.; Otchere, I.D.; Morgan, P.; Musah, A.B.; Siam, I.M.; Asandem, D.; Afum, T.; Asare, P.; Asante-Poku, A.; Kusi, K.A.; Gagneux, S.; Yeboah-Manu, D.
    Findings from previous comparative genomics studies of the Mycobacterium tuberculosis complex (MTBC) suggest genomic variation among the genotypes may have phenotypic implications. We investigated the diversity in the phenotypic profiles of the main prevalent MTBC genotypes in West Africa. Thirty-six whole genome sequenced drug susceptible MTBC isolates belonging to lineages 4, 5 and 6 were included in this study. The isolates were phenotypically characterized for urease activity, tween hydrolysis, Thiophen-2- Carboxylic Acid Hydrazide (TCH) susceptibility, nitric oxide production, and growth rate in both liquid (7H9) and solid media (7H11 and Lo¨wenstein–Jensen (L-J)). Lineage 4 isolates showed the highest growth rate in both liquid (p = 0.0003) and on solid (L-J) media supplemented with glycerol (p<0.001) or pyruvate (p = 0.005). L6 isolates optimally utilized pyruvate compared to glycerol (p<0.001), whereas L5 isolates grew similarly on both media (p = 0.05). Lineage 4 isolates showed the lowest average time to positivity (TTP) (p = 0.01; Average TTP: L4 = 15days, L5 = 16.7days, L6 = 29.7days) and the highest logCFU/mL (p = 0.04; average logCFU/mL L4 = 5.9, L5 = 5.0, L6 = 4.4) on 7H11 supplemented with glycerol, but there was no significant difference in growth on 7H11 supplemented with pyruvate (p = 0.23). The highest release of nitrite was recorded for L5 isolates, followed by L4 and L6 isolates. However, the reverse was observed in the urease activity for the lineages. All isolates tested were resistant to TCH except for one L6 isolate. Comparative genomic analyses revealed several mutations that might explain the diverse phenotypic profiles of these isolates. Our findings showed significant phenotypic diversity among the MTBC lineages used for this study.
  • Thumbnail Image
    Item
    Whole Genome Sequencing and Spatial Analysis Identifies Recent Tuberculosis Transmission Hotspots in Ghana
    (Frontiers in Medicine, 2020-05-19) Asare, P.; Otchere, I.D.; Bedeley, E.; Brites, D.; Loiseau, C.; Baddoo, N.A.; Asante-Poku, A.; Osei-Wusu, S.; Prah, D.A.; Borrell, S.; Reinhard, M.; Forson, A.; Koram, K.A.; Gagneux, S.; Yeboah-Manu, D.
    Whole genome sequencing (WGS) is progressively being used to investigate the transmission dynamics of Mycobacterium tuberculosis complex (MTBC). We used WGS analysis to resolve traditional genotype clusters and explored the spatial distribution of confirmed recent transmission clusters. Bacterial genomes from a total of 452 MTBC isolates belonging to large traditional clusters from a population-based study spanning July 2012 and December 2015 were obtained through short read next-generation sequencing using the illumina HiSeq2500 platform. We performed clustering and spatial analysis using specified R packages and ArcGIS. Of the 452 traditional genotype clustered genomes, 314 (69.5%) were confirmed clusters with a median cluster size of 7.5 genomes and an interquartile range of 4–12. Recent tuberculosis (TB) transmission was estimated as 24.7%. We confirmed the wide spread of a Cameroon sub-lineage clone with a cluster size of 78 genomes predominantly from the Ablekuma sub-district of Accra metropolis. More importantly, we identified a recent transmission cluster associated with isoniazid resistance belonging to the Ghana sub-lineage of lineage 4. WGS was useful in detecting unsuspected outbreaks; hence, we recommend its use not only as a research tool but as a surveillance tool to aid in providing the necessary guided steps to track, monitor, and control TB.
  • Thumbnail Image
    Item
    Current perspectives in drug discovery against tuberculosis from natural products
    (International Journal of Mycobacteriology, 2015-09) Nguta, J.M.; Appiah-Opong, R.; Nyarko, A.K.; Yeboah-Manu, D.; Addo, P.G.A.
    Currently, one third of the world's population is latently infected with Mycobacterium tuberculosis (MTB), while 8.9-9.9 million new and relapse cases of tuberculosis (TB) are reported yearly. The renewed research interests in natural products in the hope of discovering new and novel antitubercular leads have been driven partly by the increased incidence of multidrug-resistant strains of MTB and the adverse effects associated with the first- and second-line antitubercular drugs. Natural products have been, and will continue to be a rich source of new drugs against many diseases. The depth and breadth of therapeutic agents that have their origins in the secondary metabolites produced by living organisms cannot be compared with any other source of therapeutic agents. Discovery of new chemical molecules against active and latent TB from natural products requires an interdisciplinary approach, which is a major challenge facing scientists in this field. In order to overcome this challenge, cutting edge techniques in mycobacteriology and innovative natural product chemistry tools need to be developed and used in tandem. The present review provides a cross-linkage to the most recent literature in both fields and their potential to impact the early phase of drug discovery against TB if seamlessly combined. © 2015 Asian African Society for Mycobacteriology.
  • Item
    Significant under expression of the DosR regulon in M. tuberculosis complex lineage 6 in sputum
    (Tuberculosis, 2017-05) Ofori-Anyinam, B.; Dolganov, G.; Van, T.; Davis, J.L.; Walter, N.D.; Garcia, B.J.; Voskuil, M.; Fissette, K.; Diels, M.; Driesen, M.; Meehan, C.J.; Yeboah-Manu, D.; Coscolla, M.; Gagneux, S.; Antonio, M.; Schoolnik, G.; Gehre, F.; de Jong, B.C.
    Mycobacterium africanum lineage (L) 6 is an important pathogen in West Africa, causing up to 40% of pulmonary tuberculosis (TB). The biology underlying the clinical differences between M. africanum and M. tuberculosis sensu stricto remains poorly understood. We performed ex vivo expression of 2179 genes of the most geographically dispersed cause of human TB, M. tuberculosis L4 and the geographically restricted, M. africanum L6 directly from sputa of 11 HIV-negative TB patients from The Gambia who had not started treatment. The DosR regulon was the most significantly decreased category in L6 relative to L4. Further, we identified nonsynonymous mutations in major DosR regulon genes of 44 L6 genomes of TB patients from The Gambia and Ghana. Using Lebek's test, we assessed differences in oxygen requirements for growth. L4 grew only at the aerobic surface while L6 grew throughout the medium. In the host, the DosR regulon is critical for M. tuberculosis in adaptation to oxygen limitation. However, M. africanum L6 appears to have adapted to growth under hypoxic conditions or to different biological niches. The observed under expression of DosR in L6 fits with the genomic changes in DosR genes, microaerobic growth and the association with extrapulmonary disease. © 2017 The Authors
  • Item
    Reduced transmission of Mycobacterium africanum compared to Mycobacterium tuberculosis in urban West Africa
    (International Journal of Infectious Diseases, 2018-08) Asare, P.; Asante-Poku, A.; Prah, D.A.; Borrell, S.; Osei-Wusu, S.; Otchere, I.D.; Forson, A.; Adjapong, G.; Koram, K.A.; Gagneux, S.; Yeboah-Manu, D.
    Objective: Understanding transmission dynamics is useful for tuberculosis (TB) control. A population-based molecular epidemiological study was conducted to determine TB transmission in Ghana. Methods: Mycobacterium tuberculosis complex (MTBC) isolates obtained from prospectively sampled pulmonary TB patients between July 2012 and December 2015 were characterized using spoligotyping and standard 15-locus mycobacterial interspersed repetitive unit variable number tandem repeat (MIRU-VNTR) typing for transmission studies. Results: Out of 2309 MTBC isolates, 1082 (46.9%) unique cases were identified, with 1227 (53.1%) isolates belonging to one of 276 clusters. The recent TB transmission rate was estimated to be 41.2%. Whereas TB strains of lineage 4 belonging to M. tuberculosis showed a high recent transmission rate (44.9%), reduced recent transmission rates were found for lineages of Mycobacterium africanum (lineage 5, 31.8%; lineage 6, 24.7%). Conclusions: The study findings indicate high recent TB transmission, suggesting the occurrence of unsuspected outbreaks in Ghana. The observed reduced transmission rate of M. africanum suggests other factor(s) (host/environmental) may be responsible for its continuous presence in West Africa. © 2018 The Author(s)
  • Item
    Out-of-Africa migration and Neolithic coexpansion of Mycobacterium tuberculosis with modern humans
    (Nature Genetics, 2013-09) Comas, I.; Coscolla, M.; Luo, T.; Borrell, S.; Holt, K.E.; Kato-Maeda, M.; Parkhill, J.; Malla, B.; Berg, S.; Thwaites, G.; Yeboah-Manu, D.; Bothamley, G.; Mei, J.; Wei, L.; Bentley, S.; Harris, S.R.; Niemann, S.; Diel, R.; Aseffa, A.; Gao, Q.; Young, D.; Gagneux, S.
    Tuberculosis caused 20% of all human deaths in the Western world between the seventeenth and nineteenth centuries and remains a cause of high mortality in developing countries. In analogy to other crowd diseases, the origin of human tuberculosis has been associated with the Neolithic Demographic Transition, but recent studies point to a much earlier origin. We analyzed the whole genomes of 259 M. Tuberculosis complex (MTBC) strains and used this data set to characterize global diversity and to reconstruct the evolutionary history of this pathogen. Coalescent analyses indicate that MTBC emerged about 70,000 years ago, accompanied migrations of anatomically modern humans out of Africa and expanded as a consequence of increases in human population density during the Neolithic period. This long coevolutionary history is consistent with MTBC displaying characteristics indicative of adaptation to both low and high host densities. © 2013 Nature America, Inc. All rights reserved.
  • Item
    Towards host-directed therapies for tuberculosis
    (Nature Reviews Drug Discovery, 2015-08) Wejse, C.; Petersen, E.; Kaleebu, P.; Oliver, M.; Craig, G.; Corrah, T.; Tientcheu, L.; Antonio, M.; Rao, M.; McHugh, T.D.; Sheikh, A.; Zumla, A.; Maeurer, M.; Chakaya, J.; Hoelscher, M.; Ntoumi, F.; Rustomjee, R.; Vilaplana, C.; Yeboah-Manu, D.; Rasolofo, V.; Munderi, P.; Singh, N.; Aklillu, E.; Padayatchi, N.; Macete, E.; Kapata, N.; Mulenga, M.; Kibiki, G.; Mfinanga, S.; Nyirenda, T.; Maboko, L.; Garcia-Basteiro, A.; Rakotosamimanana, N.; Bates, M.; Mwaba, P.; Reither, K.; Gagneux, S.; Edwards, S.; Mfinanga, E.; Abdulla, S.; Cardona, P.-J; Russell, J.B.W.; Gant, V.; Noursadeghi, M.; Elkington, P.; Bonnet, M.; Menendez, C.; Dieye, T.N.; Diarra, B.; Maiga, A.; Aseffa, A.; Parida, S.; Ippolito, G.; Ramjee, G.; Kaufmann, S.H.E.; Churchyard, G.; Steyn, A.; Grobusch, M.; Sanne, I.; Martinson, N.; Madansein, R.; Wilkinson, R.J.; Mayosi, B.; Schito, M.; Wallis, R.S.
    The treatment of tuberculosis is based on combinations of drugs that directly target Mycobacterium tuberculosis. A new global initiative is now focusing on a complementary approach of developing adjunct host-directed therapies