Molecular epidemiology and drug susceptibility profiles of Mycobacterium tuberculosis complex isolates from Northern Ghana

Asare, Prince; Osei-Wusu, Stephen; Morgan, Portia; Afum, Theophilus; Asandem, Diana Asema; Otchere, Isaac Darko; Ofori, Linda Aurelia; Obiri‐Danso, Kwasi; Kock, Richard; Asante-Poku, Adwoa; Yeboah-Manu, Dorothy

doi:10.1016/j.ijid.2021.07.020

Cited by 5 publications

(9 citation statements)

References 63 publications

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“…Analysis of spoligotypes obtained from both human and animal origin in the region showed clustering of some spoligotypes (SIT1037/SB0944, SIT3760/SB1410, and SIT2813/SB1027) ( Fig 8 ) [ 38 ]. Three of the four human M .…”

Section: Resultsmentioning

confidence: 99%

“…Phylogenetic analysis of MTBC isolates from this study and previous studies by Acquah et al , (2021) in patients with pulmonary tuberculosis showed three out of the four clinical M . bovis isolates [ 38 ] had the same spoligotype pattern as the animal isolates and one (1) M . africanum (L6) animal isolates had the same spoligotype pattern as the human isolates.…”

Section: Discussionmentioning

confidence: 99%

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Molecular epidemiology of bovine tuberculosis in Northern Ghana identifies several uncharacterized bovine spoligotypes and suggests possible zoonotic transmission

et al. 2022

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Objective We conducted an abattoir-based cross-sectional study in the five administrative regions of Northern Ghana to determine the distribution of bovine tuberculosis (BTB) among slaughtered carcasses and identify the possibility of zoonotic transmission. Methods Direct smear microscopy was done on 438 tuberculosis-like lesions from selected cattle organs and cultured on Lowenstein-Jensen media. Acid-fast bacilli (AFB) isolates were confirmed as members of the Mycobacterium tuberculosis complex (MTBC) by PCR amplification of IS6110 and rpoß. Characterization and assignment into MTBC lineage and sub-lineage were done by spoligotyping, with the aid of the SITVIT2, miruvntrplus and mbovis.org databases. Spoligotype data was compared to that of clinical M. bovis isolates from the same regions to identify similarities. Results A total of 319/438 (72.8%) lesion homogenates were smear positive out of which, 84.6% (270/319) had microscopic grade of at least 1+ for AFB. Two hundred and sixty-five samples (265/438; 60.5%) were culture positive, of which 212 (80.0%) were MTBC. Approximately 16.7% (34/203) of the isolates with correctly defined spoligotypes were negative for IS6110 PCR but were confirmed by rpoß. Spoligotyping characterized 203 isolates as M. bovis (198, 97.5%), M. caprae (3, 1.5%), M. tuberculosis (Mtbss) lineage (L) 4 Cameroon sub-lineage, (1, 0.5%), and M. africanum (Maf) L6 (1, 0.5%). A total of 53 unique spoligotype patterns were identified across the five administrative regions (33 and 28 were identified as orphan respectively by the SITVIT2 and mbovis.org databases), with the most dominant spoligotype being SIT1037/ SB0944 (77/203, 37.93%). Analysis of the bovine and human M. bovis isolates showed 75% (3/4) human M. bovis isolates sharing the same spoligotype pattern with the bovine isolates. Conclusion Our study identified that approximately 29% of M. bovis strains causing BTB in Northern Ghana are caused by uncharacterized spoligotypes. Our findings suggest possible zoonotic transmission and highlight the need for BTB disease control in Northern Ghana.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Molecular epidemiology of bovine tuberculosis in Northern Ghana identifies several uncharacterized bovine spoligotypes and suggests possible zoonotic transmission

et al. 2022

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“…Genes involved in drug resistance are also part of this set. Drug-resistant TB is a major challenge, and hence genes involved in drug resistance in Maf “total-cluster-specific-SNPs” were annotated even though drug resistance is rare in Maf as compared to M.tuberculosis ( Asante-Poku et al, 2015 ; Acquah et al, 2021 ). A total of 24 genes involved in drug resistance that contain 79 SNPs were found to be part of L6-“ total-cluster-specific ” SNPs ( Supplementary Table S14 ).…”

Section: Resultsmentioning

confidence: 99%

“…SNPs belonging to genes involved in drug resistance accounted for ∼1% of the total SNP set in both lineages. They were retained as the prevalence of drug resistance in Maf is very rare ( Asante-Poku et al, 2015 ; Acquah et al, 2021 ). The “ core-sub-cluster-specific ” SNPs were derived by taking into account the “ total-cluster-specific-SNPs ”.…”

Section: Discussionmentioning

confidence: 99%

Understanding the Genetic Diversity of Mycobacterium africanum Using Phylogenetics and Population Genomics Approaches

et al. 2022

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A total of two lineages of Mycobacterium tuberculosis var. africanum (Maf), L5 and L6, which are members of the Mycobacterium tuberculosis complex (MTBC), are responsible for causing tuberculosis in West Africa. Regions of difference (RDs) are usually used for delineation of MTBC. With increased data availability, single nucleotide polymorphisms (SNPs) promise to provide better resolution. Publicly available 380 Maf samples were analyzed for identification of “core-cluster-specific-SNPs,” while additional 270 samples were used for validation. RD-based methods were used for lineage-assignment, wherein 31 samples remained unidentified. The genetic diversity of Maf was estimated based on genome-wide SNPs using phylogeny and population genomics approaches. Lineage-based clustering (L5 and L6) was observed in the whole genome phylogeny with distinct sub-clusters. Population stratification using both model-based and de novo approaches supported the same observations. L6 was further delineated into three sub-lineages (L6.1–L6.3), whereas L5 was grouped as L5.1 and L5.2 based on the occurrence of RD711. L5.1 and L5.2 were further divided into two (L5.1.1 and L5.1.2) and four (L5.2.1–L5.2.4) sub-clusters, respectively. Unassigned samples could be assigned to definite lineages/sub-lineages based on clustering observed in phylogeny along with high-confidence posterior membership scores obtained during population stratification. Based on the (sub)-clusters delineated, “core-cluster-specific-SNPs” were derived. Synonymous SNPs (137 in L5 and 128 in L6) were identified as biomarkers and used for validation. Few of the cluster-specific missense variants in L5 and L6 belong to the central carbohydrate metabolism pathway which include His6Tyr (Rv0946c), Glu255Ala (Rv1131), Ala309Gly (Rv2454c), Val425Ala and Ser112Ala (Rv1127c), Gly198Ala (Rv3293) and Ile137Val (Rv0363c), Thr421Ala (Rv0896), Arg442His (Rv1248c), Thr218Ile (Rv1122), and Ser381Leu (Rv1449c), hinting at the differential growth attenuation. Genes harboring multiple (sub)-lineage-specific “core-cluster” SNPs such as Lys117Asn, Val447Met, and Ala455Val (Rv0066c; icd2) present across L6, L6.1, and L5, respectively, hinting at the association of these SNPs with selective advantage or host-adaptation. Cluster-specific SNPs serve as additional markers along with RD-regions for Maf delineation. The identified SNPs have the potential to provide insights into the genotype–phenotype correlation and clues for endemicity of Maf in the African population.

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“…The association between M . africanum infection and elder patients was also reported in Ghana [ 63 ] and with lower body mass index individuals in Mali [ 64 ]. However, a clear association between M .…”

Section: Tb Caused By M Africanum ...mentioning

confidence: 90%

Tuberculosis caused by Mycobacterium africanum: Knowns and unknowns

Silva

Cá²,

Osório³

et al. 2022

PLoS Pathog

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Tuberculosis (TB), one of the deadliest threats to human health, is mainly caused by 2 highly related and human-adapted bacteria broadly known as Mycobacterium tuberculosis and Mycobacterium africanum. Whereas M. tuberculosis is widely spread, M. africanum is restricted to West Africa, where it remains a significant cause of tuberculosis. Although several differences have been identified between these 2 pathogens, M. africanum remains a lot less studied than M. tuberculosis. Here, we discuss the genetic, phenotypic, and clinical similarities and differences between strains of M. tuberculosis and M. africanum. We also discuss our current knowledge on the immune response to M. africanum and how it possibly articulates with distinct disease progression and with the geographical restriction attributed to this pathogen. Understanding the functional impact of the diversity existing in TB-causing bacteria, as well as incorporating this diversity in TB research, will contribute to the development of better, more specific approaches to tackle TB.

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Molecular epidemiology and drug susceptibility profiles of Mycobacterium tuberculosis complex isolates from Northern Ghana

Cited by 5 publications

References 63 publications

Molecular epidemiology of bovine tuberculosis in Northern Ghana identifies several uncharacterized bovine spoligotypes and suggests possible zoonotic transmission

Molecular epidemiology of bovine tuberculosis in Northern Ghana identifies several uncharacterized bovine spoligotypes and suggests possible zoonotic transmission

Understanding the Genetic Diversity of Mycobacterium africanum Using Phylogenetics and Population Genomics Approaches

Tuberculosis caused by Mycobacterium africanum: Knowns and unknowns

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