Mycobacterium africanum

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Sebastien Gagneux - One of the best experts on this subject based on the ideXlab platform.

  • phylogenomics of Mycobacterium africanum reveals a new lineage and a complex evolutionary history
    2021
    Co-Authors: Mireia Coscolla, Chloé Loiseau, Sebastien Gagneux, Sonia Borrell, Fabrizio Menardo, Paula Ruizrodriguez
    Abstract:

    Human tuberculosis (TB) is caused by members of the Mycobacterium tuberculosis complex (MTBC). The MTBC comprises several human-adapted lineages known as M. tuberculosis sensu stricto, as well as two lineages (L5 and L6) traditionally referred to as Mycobacterium africanum. Strains of L5 and L6 are largely limited to West Africa for reasons unknown, and little is known of their genomic diversity, phylogeography and evolution. Here, we analysed the genomes of 350 L5 and 320 L6 strains, isolated from patients from 21 African countries, plus 5 related genomes that had not been classified into any of the known MTBC lineages. Our population genomic and phylogeographical analyses showed that the unclassified genomes belonged to a new group that we propose to name MTBC lineage 9 (L9). While the most likely ancestral distribution of L9 was predicted to be East Africa, the most likely ancestral distribution for both L5 and L6 was the Eastern part of West Africa. Moreover, we found important differences between L5 and L6 strains with respect to their phylogeographical substructure and genetic diversity. Finally, we could not confirm the previous association of drug-resistance markers with lineage and sublineages. Instead, our results indicate that the association of drug resistance with lineage is most likely driven by sample bias or geography. In conclusion, our study sheds new light onto the genomic diversity and evolutionary history of M. africanum, and highlights the need to consider the particularities of each MTBC lineage for understanding the ecology and epidemiology of TB in Africa and globally.

  • reduced transmission of Mycobacterium africanum compared to Mycobacterium tuberculosis in urban west africa
    2017
    Co-Authors: Prince Asare, Audrey Forson, Isaac Darko Otchere, Adwoa Asantepoku, Sonia Borrell, Stephen Oseiwusu, Diana Ahu Prah, Gloria Adjapong, Kwadwo A Koram, Sebastien Gagneux
    Abstract:

    Understanding transmission dynamics is useful for tuberculosis (TB) control. We conducted a population-based molecular epidemiological study to understand TB transmission in Ghana. Mycobacterium tuberculosis complex (MTBC) isolates obtained from prospectively-sampled pulmonary TB patients between July, 2012 and December, 2015 were confirmed as MTBC using IS6110 PCR. MTBC lineages were identified by large sequence polymorphism and single nucleotide polymorphism assays and further characterized using spoligotyping and standard 15-loci MIRU-VNTR typing. We used the n-1 method to estimate recent TB transmission and identified associated risk factors using logistic regression analysis. Out of 2,309 MTBC isolates, we identified 1,082 (46.9%) single cases with 1,227 (53.1%) isolates belonging to one of 276 clustered cases (clustering range; 2-35). Recent TB transmission rate was estimated to be 41.2%. While we see no significant difference in the recent transmission rates between lineages of Mycobacterium africanum (lineage 5 (31.8%); lineage 6 (24.7%), p=0.118), we found that lineage-4 belonging to the M. tuberculosis transmitted significantly higher (44.9%, p

  • the first population structure and comparative genomics analysis of Mycobacterium africanum strains from ghana reveals higher diversity of lineage 5
    2016
    Co-Authors: Isaac Darko Otchere, Sebastien Gagneux, Adwoa Asantepoku, Stephen Oseiwusu, Kwadwo A Koram, Simon R Harris, Sanches L Busso, Julian Parkhill, Dorothy Yeboahmanu
    Abstract:

    Abstract Objective/background Mycobacterium africanum (MAF) remains an important TB causing pathogen in West Africa; however, little is known about its population structure and actual diversity which may have implications for diagnostics and vaccines. We carried out comparative genomics analysis of candidate Mycobacterium tuberculosis (MTB) and MAF using whole genome sequencing. Methods Clinical MTB complex strains (n = 187) comprising L4 (n = 22), L5 (n = 126), and L6 (n = 39) isolated over 8 years from Ghana were whole genome sequenced. The reads were mapped onto a reference genome for phylogenetic and functional genomics analysis. A maximum likelihood tree with 100 bootstraps was constructed from the single nucleotide polymorphisms (SNPs) found using RAxML and clustered with hierBAPS. A total of 147 (18 L4, 36 L6, and 93 L5) of the genomes were de novo assembled and annotated for comparative pangenome analysis using Roary. Results The population structure of MAF revealed at least five clusters of L5 as compared to three for L6. We also identified a group of three multi-drug-resistants (MDRs) within a single cluster of L5 strains from Southern Ghana isolated in 2013. Among the global collection of MTB complex, there were four Ghana-specific L5 clusters of which one (L5.1.1) had traits of clonal expansion. From the 5947 pan genes extracted from the collection, 3215 (54.1%) were core to all the 147 genomes whereas 719 (12.1%) were found in single genomes. Most of the variable genes were PE-PGRS/PPE (1,281) duplicates of other genes (431). The genome degradation was more pronounced in Lineages 4 and 6 as compared to Lineage 5. We identified the absence of some unique genes among specific lineages and/or clades with possible clinical implications. For example, mpt64 and mlaD encoding respectively an immunogenic protein and a mammalian cell entry protein were missing from all L6 genomes. In addition, all L5 strains had an amino acid substitution I43 N within the mpt64 gene. Analysis of SNPs within some genes encoding proteins for substrate metabolism, ion transport and secretory systems showed higher proportion of SNPs among L6 compared to L5 and L4. We also identified a number of lineage/sublineage specific SNPs and indels that may be utilized in rapid PCR based genotyping of MTB complex. Conclusion This work emphasizes on the possibility that the mpt64-based rapid diagnostic kit would not be effective in MAF endemic settings. More mutations in ESAT-6 secretory system of MAF compared to MTB sensu stricto can affect efficacy of ESAT-6-based vaccines in the future.

  • Mycobacterium africanum is associated with patient ethnicity in ghana
    2015
    Co-Authors: Adwoa Asantepoku, Isaac Darko Otchere, Dorothy Yeboahmanu, Samuel Yaw Aboagye, David Stucki, Jan Hattendorf, Sonia Borrell, Julia Feldmann, Emelia Danso, Sebastien Gagneux
    Abstract:

    Mycobacterium africanum is a member of the Mycobacterium tuberculosis complex (MTBC) and an important cause of human tuberculosis in West Africa that is rarely observed elsewhere. Here we genotyped 613 MTBC clinical isolates from Ghana, and searched for associations between the different phylogenetic lineages of MTBC and patient variables. We found that 17.1% (105/613) of the MTBC isolates belonged to M. africanum, with the remaining belonging to M. tuberculosis sensu stricto. No M. bovis was identified in this sample. M. africanum was significantly more common in tuberculosis patients belonging to the Ewe ethnic group (adjusted odds ratio: 3.02; 95% confidence interval: 1.67–5.47, p<0.001). Stratifying our analysis by the two phylogenetic lineages of M. africanum (i.e. MTBC Lineages 5 and 6) revealed that this association was mainly driven by Lineage 5 (also known as M. africanum West Africa 1). Our findings suggest interactions between the genetic diversity of MTBC and human diversity, and offer a possible explanation for the geographical restriction of M. africanum to parts of West Africa.

  • Mycobacterium africanum review of an important cause of human tuberculosis in west africa
    2010
    Co-Authors: Bouke C De Jong, Martin Antonio, Sebastien Gagneux
    Abstract:

    Mycobacterium africanum consists of two phylogenetically distinct lineages within the Mycobacterium tuberculosis complex, known as M. africanum West African 1 and M. africanum West African 2. These lineages are restricted to West Africa, where they cause up to half of human pulmonary tuberculosis. In this review we discuss the definition of M. africanum, describe the prevalence and restricted geographical distribution of M. africanum West African 1 and 2, review the occurrence of M. africanum in animals, and summarize the phenotypic differences described thus far between M. africanum and M. tuberculosis sensu stricto.

Isaac Darko Otchere - One of the best experts on this subject based on the ideXlab platform.

  • phylogenomics of Mycobacterium africanum reveals a new lineage and a complex evolutionary history
    2020
    Co-Authors: Mireia Coscolla, Chloé Loiseau, Daniela Brites, Sonia Borrell, Fabrizio Menardo, Isaac Darko Otchere
    Abstract:

    Abstract Human tuberculosis is caused by members of the Mycobacterium tuberculosis Complex (MTBC). The MTBC comprises several human-adapted lineages known as M. tuberculosis sensu stricto as well as two lineages (L5 and L6) traditionally referred to as M. africanum. Strains of L5 and L6 are largely limited to West Africa for reasons unknown, and little is known on their genomic diversity, phylogeography and evolution. Here, we analyzed the genomes of 365 L5 and 326 L6 strains, plus five related genomes that had not been classified into any of the known MTBC lineages, isolated from patients from 21 African countries. Our population genomic and phylogeographical analyses show that the unclassified genomes belonged to a new group that we propose to name MTBC Lineage 9 (L9). While the most likely ancestral distribution of L9 was predicted to be East Africa, the most likely ancestral distribution for both L5 and L6 was the Eastern part of West Africa. Moreover, we found important differences between L5 and L6 strains with respect to their phylogeographical substructure, genetic diversity and association with drug resistance. In conclusion, our study sheds new light onto the genomic diversity and evolutionary history of M. africanum, and highlights the need to consider the particularities of each MTBC lineage for understanding the ecology and epidemiology of tuberculosis in Africa and globally.

  • tb diabetes co morbidity in ghana the importance of Mycobacterium africanum infection
    2019
    Co-Authors: Adwoa Asantepoku, Prince Asare, Nyonuku Akosua Baddoo, Audrey Forson, Isaac Darko Otchere, Samuel Yaw Aboagye, Emelia Danso, Stephen Oseiwusu, Pius Mawutor Klevor, Kwadwo A Koram
    Abstract:

    BACKGROUND Diabetes Mellitus (DM) is a known risk factor for tuberculosis (TB) but little is known on TB-Diabetes Mellitus (TBDM) co-morbidity in Sub-Saharan Africa. METHODS Consecutive TB cases registered at a tertiary facility in Ghana were recruited from September 2012 to April 2016 and screened for DM using random blood glucose and glycated hemoglobin (HbA1c) level. TB patients were tested for other clinical parameters including HIV co-infection and TB lesion location. Mycobacterial isolates obtained from collected sputum samples were characterized by standard methods. Associations between TBDM patients' epidemiological as well as microbiological variables were assessed. RESULTS The prevalence of DM at time of diagnosis among 2990 enrolled TB cases was 9.4% (282/2990). TBDM cases were significantly associated with weight loss, poor appetite, night sweat and fatigue (p<0.001) and were more likely (p<0.001) to have lower lung cavitation 85.8% (242/282) compared to TB Non-Diabetic (TBNDM) patients 3.3% (90/2708). We observed 22.3% (63/282) treatment failures among TBDM patients compared to 3.8% (102/2708) among TBNDM patients (p<0.001). We found no significant difference in the TBDM burden attributed by M. tuberculosis sensu stricto (Mtbss) and Mycobacterium africanum (Maf) and (Mtbss; 176/1836, 9.6% and Maf; 53/468, 11.3%, p = 0.2612). We found that diabetic individuals were suggestively likely to present with TB caused by M. africanum Lineage 6 as opposed to Mtbss (odds ratio (OR) = 1.52; 95% confidence interval (CI): 0.92-2.42, p = 0.072). CONCLUSION Our findings confirms the importance of screening for diabetes during TB diagnosis and highlights the association between genetic diversity and diabetes. in Ghana.

  • Distribution of Mycobacterium africanum (Maf) among TBDM and TBNDM Patients.
    2019
    Co-Authors: Adwoa Asante-poku, Prince Asare, Nyonuku Akosua Baddoo, Audrey Forson, Pius Klevor, Isaac Darko Otchere, Sammy Yaw Aboagye, Stephen Osei-wusu, Emelia Konadu Danso, Kwadwo Koram
    Abstract:

    Distribution of Mycobacterium africanum (Maf) among TBDM and TBNDM Patients.

  • TB-diabetes co-morbidity in Ghana: The importance of Mycobacterium africanum infection
    2019
    Co-Authors: Adwoa Asante-poku, Prince Asare, Nyonuku Akosua Baddoo, Audrey Forson, Pius Klevor, Isaac Darko Otchere, Sammy Yaw Aboagye, Stephen Osei-wusu, Emelia Konadu Danso, Kwadwo Koram
    Abstract:

    BackgroundDiabetes Mellitus (DM) is a known risk factor for tuberculosis (TB) but little is known on TB-Diabetes Mellitus (TBDM) co-morbidity in Sub-Saharan Africa.MethodsConsecutive TB cases registered at a tertiary facility in Ghana were recruited from September 2012 to April 2016 and screened for DM using random blood glucose and glycated hemoglobin (HbA1c) level. TB patients were tested for other clinical parameters including HIV co-infection and TB lesion location. Mycobacterial isolates obtained from collected sputum samples were characterized by standard methods. Associations between TBDM patients’ epidemiological as well as microbiological variables were assessed.ResultsThe prevalence of DM at time of diagnosis among 2990 enrolled TB cases was 9.4% (282/2990). TBDM cases were significantly associated with weight loss, poor appetite, night sweat and fatigue (p

  • reduced transmission of Mycobacterium africanum compared to Mycobacterium tuberculosis in urban west africa
    2018
    Co-Authors: Prince Asare, Audrey Forson, Isaac Darko Otchere, Adwoa Asantepoku, Sonia Borrell, Stephen Oseiwusu, Diana Ahu Prah, Gloria Adjapong, Kwadwo A Koram
    Abstract:

    Abstract 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.

Adwoa Asantepoku - One of the best experts on this subject based on the ideXlab platform.

  • tb diabetes co morbidity in ghana the importance of Mycobacterium africanum infection
    2019
    Co-Authors: Adwoa Asantepoku, Prince Asare, Nyonuku Akosua Baddoo, Audrey Forson, Isaac Darko Otchere, Samuel Yaw Aboagye, Emelia Danso, Stephen Oseiwusu, Pius Mawutor Klevor, Kwadwo A Koram
    Abstract:

    BACKGROUND Diabetes Mellitus (DM) is a known risk factor for tuberculosis (TB) but little is known on TB-Diabetes Mellitus (TBDM) co-morbidity in Sub-Saharan Africa. METHODS Consecutive TB cases registered at a tertiary facility in Ghana were recruited from September 2012 to April 2016 and screened for DM using random blood glucose and glycated hemoglobin (HbA1c) level. TB patients were tested for other clinical parameters including HIV co-infection and TB lesion location. Mycobacterial isolates obtained from collected sputum samples were characterized by standard methods. Associations between TBDM patients' epidemiological as well as microbiological variables were assessed. RESULTS The prevalence of DM at time of diagnosis among 2990 enrolled TB cases was 9.4% (282/2990). TBDM cases were significantly associated with weight loss, poor appetite, night sweat and fatigue (p<0.001) and were more likely (p<0.001) to have lower lung cavitation 85.8% (242/282) compared to TB Non-Diabetic (TBNDM) patients 3.3% (90/2708). We observed 22.3% (63/282) treatment failures among TBDM patients compared to 3.8% (102/2708) among TBNDM patients (p<0.001). We found no significant difference in the TBDM burden attributed by M. tuberculosis sensu stricto (Mtbss) and Mycobacterium africanum (Maf) and (Mtbss; 176/1836, 9.6% and Maf; 53/468, 11.3%, p = 0.2612). We found that diabetic individuals were suggestively likely to present with TB caused by M. africanum Lineage 6 as opposed to Mtbss (odds ratio (OR) = 1.52; 95% confidence interval (CI): 0.92-2.42, p = 0.072). CONCLUSION Our findings confirms the importance of screening for diabetes during TB diagnosis and highlights the association between genetic diversity and diabetes. in Ghana.

  • reduced transmission of Mycobacterium africanum compared to Mycobacterium tuberculosis in urban west africa
    2018
    Co-Authors: Prince Asare, Audrey Forson, Isaac Darko Otchere, Adwoa Asantepoku, Sonia Borrell, Stephen Oseiwusu, Diana Ahu Prah, Gloria Adjapong, Kwadwo A Koram
    Abstract:

    Abstract 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.

  • reduced transmission of Mycobacterium africanum compared to Mycobacterium tuberculosis in urban west africa
    2017
    Co-Authors: Prince Asare, Audrey Forson, Isaac Darko Otchere, Adwoa Asantepoku, Sonia Borrell, Stephen Oseiwusu, Diana Ahu Prah, Gloria Adjapong, Kwadwo A Koram, Sebastien Gagneux
    Abstract:

    Understanding transmission dynamics is useful for tuberculosis (TB) control. We conducted a population-based molecular epidemiological study to understand TB transmission in Ghana. Mycobacterium tuberculosis complex (MTBC) isolates obtained from prospectively-sampled pulmonary TB patients between July, 2012 and December, 2015 were confirmed as MTBC using IS6110 PCR. MTBC lineages were identified by large sequence polymorphism and single nucleotide polymorphism assays and further characterized using spoligotyping and standard 15-loci MIRU-VNTR typing. We used the n-1 method to estimate recent TB transmission and identified associated risk factors using logistic regression analysis. Out of 2,309 MTBC isolates, we identified 1,082 (46.9%) single cases with 1,227 (53.1%) isolates belonging to one of 276 clustered cases (clustering range; 2-35). Recent TB transmission rate was estimated to be 41.2%. While we see no significant difference in the recent transmission rates between lineages of Mycobacterium africanum (lineage 5 (31.8%); lineage 6 (24.7%), p=0.118), we found that lineage-4 belonging to the M. tuberculosis transmitted significantly higher (44.9%, p

  • reduced transmission of Mycobacterium africanum compared to m tuberculosis in urban west africa
    2017
    Co-Authors: Prince Asare, Audrey Forson, Isaac Darko Otchere, Adwoa Asantepoku, Sonia Borrell, Stephen Oseiwusu, Diana Ahu Prah, Gloria Adjapong, Kwadwo A Koram
    Abstract:

    Abstract Background Understanding transmission dynamics is useful for tuberculosis (TB) control. We conducted a population-based molecular epidemiological study to understand TB transmission in Ghana. Methods Mycobacterium tuberculosis complex (MTBC) isolates obtained from prospectively-sampled pulmonary TB patients between July, 2012 and December, 2015 were confirmed as MTBC using IS6110 PCR. MTBC lineages were identified by large sequence polymorphism and single nucleotide polymorphism assays and further characterized using spoligotyping and standard 15-loci MIRU-VNTR typing. We used the n-1 method to estimate recent TB transmission and identified associated risk factors using logistic regression analysis. Findings Out of 2,309 MTBC isolates, we identified 1,082 (46·9%) single cases with 1,227 (53·1%) isolates belonging to one of 276 clustered cases (clustering range; 2-35). Recent TB transmission rate was estimated to be 41·2%. While we see no significant difference in the recent transmission rates between lineages of Mycobacterium africanum (lineage-5 (31·8%); lineage-6 (24·7%), p=0·118), we found that lineage-4 belonging to the M. tuberculosis transmitted significantly higher (44·9%, p Interpretations Our findings indicate high recent TB transmission suggesting occurrences of unsuspected outbreaks. The observed reduced transmission rate of M. africanum suggests other factor(s) may be responsible for its continuous presence in West Africa. Funding Wellcome Trust Intermediate Fellowship Grant 097134/Z/11/Z to Dorothy Yeboah-Manu.

  • comparative genomics of Mycobacterium africanum lineage 5 and lineage 6 from ghana suggests different ecological niches
    2017
    Co-Authors: Isaac Darko Otchere, Audrey Forson, Adwoa Asantepoku, Stephen Oseiwusu, Clement Laryea, Mireia Coscolla, Leonor Sanchezbuso, Conor J Meehan, Abdallah Iddrisu Yahayah, Akosua Baddoo
    Abstract:

    Mycobacterium africanum (Maf) causes up to half of human tuberculosis in West Africa, but little is known on this pathogen. We compared the genomes of 253 Maf clinical isolates from Ghana, including both L5 and L6. We found that the genomic diversity of L6 was higher than in L5, and the selection pressures differed between both groups. Regulatory proteins appeared to evolve neutrally in L5 but under purifying selection in L6. Conversely, variable T cell epitopes were under purifying selection in L5, but under positive selection in L6. Although only 10% of the T cell epitopes were variable, mutations were mostly lineage-specific. Our findings indicate that Maf L5 and L6 are genomically distinct, possibly reflecting different ecological niches.

Bouke C De Jong - One of the best experts on this subject based on the ideXlab platform.

  • the biology and epidemiology of Mycobacterium africanum
    2017
    Co-Authors: Dorothy Yeboahmanu, Bouke C De Jong, Florian Gehre
    Abstract:

    West Africa is the only region in the world where six out of seven mycobacterial lineages of human importance are endemic. In particular, two evolutionary ancient lineages, Mycobacterium africanum West Africa 1 (MTBC Lineage 5) and M. africanum West Africa 2 (MTBC Lineage 6) are of interest as they cause up to 40% of all pulmonary TB cases in some West African countries. Although these M. africanum lineages are closely related to M. tuberculosis sensu stricto lineages, they differ significantly in respect to biology, epidemiology and in their potential to cause disease in humans. Most importantly the M. africanum lineages are exclusive to West Africa. Although the exact mechanisms underlying this geographical restriction are still not understood, it is increasingly suspected that this is due to an adaptation of the bacteria to West African host populations. In this chapter, we summarize the geographical distribution of the M. africanum lineages within the region, describe biological and clinical differences and the consequent implications for TB control in West Africa. We also try to shed light on the geographical restriction, based on recently published analyses on whole genomes of M. africanum isolates.

  • differences in t cell responses between Mycobacterium tuberculosis and Mycobacterium africanum infected patients
    2014
    Co-Authors: Bouke C De Jong, Martin Antonio, Ifedayo M O Adetifa, Leopold D Tientcheu, Jayne S Sutherland, Beate Kampmann, James Jafali, Hazel M Dockrell, Martin O C Ota
    Abstract:

    In The Gambia, Mycobacterium tuberculosis (Mtb) and Mycobacterium africanum (Maf) are major causes of tuberculosis (TB). Maf is more likely to cause TB in immune suppressed individuals, implying differences in virulence. Despite this, few studies have assessed the underlying immunity to the two pathogens in human. In this study, we analyzed T-cell responses from 19 Maf- and 29 Mtb-infected HIV-negative patients before and after TB chemotherapy following overnight stimulation of whole blood with TB-specific antigens. Before treatment, percentages of early secreted antigenic target-6(ESAT-6)/culture filtrate protein-10(CFP-10) and purified protein derivative-specific single-TNF-α-producing CD4(+) and CD8(+) T cells were significantly higher while single-IL-2-producing T cells were significantly lower in Maf- compared with Mtb-infected patients. Purified protein derivative-specific polyfunctional CD4(+) T cells frequencies were significantly higher before than after treatment, but there was no difference between the groups at both time points. Furthermore, the proportion of CD3(+) CD11b(+) T cells was similar in both groups pretreatment, but was significantly lower with higher TNF-α, IL-2, and IFN-γ production in Mtb- compared with that of Maf-infected patients posttreatment. Our data provide evidence of differences in T-cell responses to two mycobacterial strains with differing virulence, providing some insight into TB pathogenesis with different Mtb strains that could be prospectively explored as biomarkers for TB protection or susceptibility.

  • correction deciphering the growth behaviour of Mycobacterium africanum
    2013
    Co-Authors: Florian Gehre, Bouke C De Jong, Jacob Otu, Kathryn Deriemer, Paola Florez De Sessions, Martin L Hibberd, Wim Mulders, Tumani Corrah, Martin Antonio
    Abstract:

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  • deciphering the growth behaviour of Mycobacterium africanum
    2013
    Co-Authors: Florian Gehre, Bouke C De Jong, Jacob Otu, Kathryn Deriemer, Paola Florez De Sessions, Martin L Hibberd, Wim Mulders, Tumani Corrah, Martin Antonio
    Abstract:

    BACKGROUND Human tuberculosis (TB) in West Africa is not only caused by M. tuberculosis but also by bacteria of the two lineages of M. africanum. For instance, in The Gambia, 40% of TB is due to infections with M. africanum West African 2. This bacterial lineage is associated with HIV infection, reduced ESAT-6 immunogenicity and slower progression to active disease. Although these characteristics suggest an attenuated phenotype of M. africanum, no underlying mechanism has been described. From the first descriptions of M. africanum in the literature in 1969, the time to a positive culture of M. africanum on solid medium was known to be longer than the time to a positive culture of M. tuberculosis. However, the delayed growth of M. africanum, which may correlate with the less virulent phenotype in the human host, has not previously been studied in detail. METHODOLOGY/PRINCIPAL FINDINGS We compared the growth rates of M. tuberculosis and M. africanum isolates from The Gambia in two liquid culture systems. M. africanum grows significantly slower than M. tuberculosis, not only when grown directly from sputa, but also in growth experiments under defined laboratory conditions. We also sequenced four M. africanum isolates and compared their whole genomes with the published M. tuberculosis H37Rv genome. M. africanum strains have several non-synonymous SNPs or frameshift mutations in genes that were previously associated with growth-attenuation. M. africanum strains also have a higher mutation frequency in genes crucial for transport of sulphur, ions and lipids/fatty acids across the cell membrane into the bacterial cell. Surprisingly, 5 of 7 operons, recently described as essential for intracellular survival of H37Rv in the host macrophage, showed at least one non-synonymously mutated gene in M. africanum. CONCLUSIONS/SIGNIFICANCE The altered growth behaviour of M. africanum might indicate a different survival strategy within host cells.

  • impaired fitness of Mycobacterium africanum despite secretion of esat 6
    2012
    Co-Authors: Tyler D Bold, Joel D Ernst, Bouke C De Jong, Daphne C Davis, Kristen K Penberthy, Laura M Cox
    Abstract:

    Mycobacterium africanum causes up to 50% of pulmonary tuberculosis in West Africa [1, 2]. A distinct lineage within the M. tuberculosis complex, M. africanum is classified by spoligotype analysis and large-sequence polymorphisms (LSPs) [3–5]. Strains previously classified biochemically as West African M. africanum (type I) share a ΔRD9 LSP and cluster phylogenetically with animal strains, including M. bovis and M. microti. West African–type strains are further subclassified into MAF1 (ΔRD711) and MAF2 (ΔRD7, RD8, RD10, and RD702). The present study concerns West African strains of M. africanum, utilizing the MAF2 clinical isolate GM041182, which has recently undergone genome sequencing. In West Africa, the prevalence of M. africanum MAF1 and MAF2 varies geographically. In The Gambia, a study of 386 smear-positive tuberculosis cases revealed a prevalence of M. africanum of 38.4%, with all M. africanum isolates categorized as MAF2 [3]. We previously reported that, although transmission rates of M. tuberculosis and M. africanum were similar, Gambian patients infected with M. africanum were less likely to develop active pulmonary disease than M. tuberculosis–infected patients during a 2-year follow-up [6]. This and the finding that M. africanum is more prevalent among malnourished, human immunodeficiency virus (HIV)–infected, and older individuals suggest that M. africanum is less virulent and more opportunistic than M. tuberculosis [1]. Mycobacterium africanum–infected individuals also have lower-frequency T-cell responses to the secreted antigen and virulence factor ESAT-6 (EsxA/Rv3875), secreted by the ESX-1 type VII secretion system [7]. In contrast, T-cell responses to another ESX-1 product, CFP-10 (EsxB/Rv3874), generally thought to be cosecreted with ESAT-6 [8], are similar among those with M. africanum and M. tuberculosis [7]. The components of ESX-1 are encoded in the RD1 locus (Rv3871–Rv3879c) and are absent from M. bovis Bacille Calmette-Guerin [9]. Because of its role in virulence [10], ESX-1 is the subject of genetic and biochemical studies that have suggested a functional model [11] and revealed the genes within the RD1 locus required for ESAT-6 and CFP-10 secretion [10, 12, 13]. The present study investigated the role of the RD1-encoded protein Rv3879c/EspK in ESX-1 secretion by M. africanum, which carries a single nucleotide deletion at base pair 427 of the Rv3879c open reading frame, resulting in a premature stop codon [7]. We hypothesized that the Rv3879c mutation results in defective secretion of ESAT-6 by M. africanum, underlying the differences in ESAT-6–specific T-cell responses and disease outcome among M. africanum–infected patients.

Nalin Rastogi - One of the best experts on this subject based on the ideXlab platform.

  • Phylogenomic analysis of the species of the Mycobacterium tuberculosis complex demonstrates that Mycobacterium africanum, Mycobacterium bovis, Mycobacterium caprae, Mycobacterium microti and Mycobacterium pinnipedii are later heterotypic synonyms of
    2018
    Co-Authors: Marco A. Riojas, Katya J. Mcgough, Cristin J. Rider-riojas, Nalin Rastogi, Manzour Hernando Hazbón
    Abstract:

    The species within the Mycobacterium tuberculosis Complex (MTBC) have undergone numerous taxonomic and nomenclatural changes, leaving the true structure of the MTBC in doubt. We used next-generation sequencing (NGS), digital DNA–DNA hybridization (dDDH), and average nucleotide identity (ANI) to investigate the relationship between these species. The type strains of Mycobacterium africanum , Mycobacterium bovis , Mycobacterium caprae , Mycobacterium microti and Mycobacterium pinnipedii were sequenced via NGS. Pairwise dDDH and ANI comparisons between these, previously sequenced MTBC type strain genomes (including ‘Mycobacterium canettii’, ‘Mycobacterium mungi’ and ‘Mycobacterium orygis’) and M. tuberculosis H37RvT were performed. Further, all available genome sequences in GenBank for species in or putatively in the MTBC were compared to H37RvT. Pairwise results indicated that all of the type strains of the species are extremely closely related to each other (dDDH: 91.2–99.2 %, ANI: 99.21–99.92 %), greatly exceeding the respective species delineation thresholds, thus indicating that they belong to the same species. Results from the GenBank genomes indicate that all the strains examined are within the circumscription of H37RvT (dDDH: 83.5–100 %). We, therefore, formally propose a union of the species of the MTBC as M. tuberculosis . M. africanum , M. bovis , M. caprae , M. microti and M. pinnipedii are reclassified as later heterotypic synonyms of M. tuberculosis . ‘M. canettii’, ‘M. mungi’, and ‘M. orygis’ are classified as strains of the species M. tuberculosis . We further recommend use of the infrasubspecific term ‘variant’ (‘var.’) and infrasubspecific designations that generally retain the historical nomenclature associated with the groups or otherwise convey such characteristics, e.g. M. tuberculosis var. bovis.

  • Mycobacterium africanum genotyping using novel spacer oligonucleotides in the direct repeat locus
    2004
    Co-Authors: Karine Brudey, Nalin Rastogi, Cristina M Gutierrez, Veronique Vincent, Linda M Parsons, Max Salfinger, Christophe Sola
    Abstract:

    This study involves a first evaluation of 25 novel spacer oligonucleotides in addition to the 43 routine spacers for molecular characterization of a panel of 65 isolates of tubercle bacilli from different geographic origins that were initially classified as Mycobacterium africanum based on phenotypic characters. The 68-spacer format defined four additional patterns, and three groups were identified. The relatively homogeneous groups A1 and A2 included strains from West Africa, and A3-1 included strains from East Africa. The presence of deletion region RD9 confirmed the reclassification of the M. africanum subtype II spoligopattern within group A3-1 as Mycobacterium tuberculosis. These isolates may represent a diverging branch of M. tuberculosis in Africa. The use of new spacers also suggested an undergoing evolution of M. africanum subtype I in West Africa. Our results showed that the strain differentiation within the M. tuberculosis complex is improved by using novel spacers, and extensive studies using new-generation spoligotyping may be helpful to better understand the evolution of M. africanum.

  • genetic diversity of Mycobacterium africanum clinical isolates based on is6110 restriction fragment length polymorphism analysis spoligotyping and variable number of tandem dna repeats
    2001
    Co-Authors: Cristina Viananiero, Christophe Sola, Veronique Vincent, Cristina Gutierrez, Ingrid Filliol, Fadila Boulahbal, Nalin Rastogi
    Abstract:

    A collection of 105 clinical isolates originally identified as Mycobacterium africanum were characterized using both phenotypic and genotyping methods. The phenotypic methods included routine determination of cultural properties and biochemical tests used to discriminate among the members of the M. tuberculosis complex, whereas genotypic characterization was based on IS6110-restriction fragment length polymorphism (IS6110-RFLP) analysis, IS1081-RFLP analysis, direct repeat-based spacer oligonucleotide typing (spoligotyping), variable number of tandem DNA repeats (VNTR), and the polymorphism of the oxyR, pncA, and mtp40 loci. The results obtained showed that a majority of M. africanum isolates were characterized by a specific spoligotyping pattern that was intermediate between those of M. tuberculosis and M. bovis, which do not hybridize with spacers 33 to 36 and spacers 39 to 43, respectively. A tentative M. africanum-specific spoligotyping signature appeared to be absence of spacers 8, 9, and 39. Based on spoligotyping, as well as the polymorphism of oxyR and pncA, a total of 24 isolates were excluded from the final study (19 were identified as M. tuberculosis, 2 were identified as M. canetti, and 3 were identified as M. bovis). The remaining 81 M. africanum isolates were efficiently subtyped in three distinct subtypes (A1 to A3) by IS6110-RFLP analysis and spoligotyping. The A1 and A2 subgroups were relatively more homogeneous upon spoligotyping than A3. Further analysis of the three subtypes by VNTR corroborated the highly homogeneous nature of the A2 subtype but showed significant variations for subtypes A1 and A3. A phylogenetic tree based on a selection of isolates representing the three subtypes using VNTR and spoligotyping alone or in combination confirmed the subtypes described as well as the heterogeneity of subtype A3.

  • activity of rifapentine and its metabolite 25 o desacetylrifapentine compared with rifampicin and rifabutin against Mycobacterium tuberculosis Mycobacterium africanum Mycobacterium bovis and m bovis bcg
    2000
    Co-Authors: Nalin Rastogi, K S Goh, Mylene Berchel, Andre Bryskier
    Abstract:

    The in vitro activity of rifapentine and its metabolite, 25-O:-desacetylrifapentine, as compared with that of rifampicin and rifabutin, was determined against Mycobacterium tuberculosis, Mycobacterium africanum, Mycobacterium bovis and M. bovis BCG. MICs were determined radiometrically and by the 1% proportional method using Middlebrook 7H11 agar. The bactericidal effect of the drugs was determined in parallel at selected concentrations. For drugsusceptible isolates of M. tuberculosis, the Bactec MICs of rifapentine and 25-O:-desacetylrifapentine were 0.03-0.06 mg/L and 0. 125-0.25 mg/L, respectively. Similar MICs were obtained for M. africanum (0.03-0.125 and 0.125-0.50 mg/L, respectively), and M. bovis (0.063-0.25 and 0.125-1.0 mg/L, respectively), but MICs were considerably lower for M. bovis BCG (0.008-0.063 mg/L for rifapentine and 0.016-0.125 mg/L for its metabolite). In general, MICs determined using 7H11 agar medium were usually one or two dilutions higher than those obtained using Bactec broth. When compared with rifampicin and rifabutin, the inhibitory activity of rifapentine for drug-susceptible isolates was roughly equal to that of rifabutin, and the inhibitory activity of 25-O:-desacetylrifapentine was comparable to that of rifampicin; however, rifapentine was somewhat more bactericidal than rifabutin at equal concentrations. Clinical isolates of M. tuberculosis with a high degree of resistance to rifampicin (MIC >/= 32 mg/L) were also highly resistant to rifabutin, rifapentine and 25-O:-desacetylrifapentine, although the MICs of rifabutin in this case were somewhat lower than the MICs of rifapentine.

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