Mycobacterium africanum—Review of an Important Cause of Human Tuberculosis in West Africa

Jong, Bouke C. de; Antonio, Martín; Gagneux, Sébastien

doi:10.1371/journal.pntd.0000744

Cited by 249 publications

(283 citation statements)

References 54 publications

(80 reference statements)

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“…M. tuberculosis is the predominant cause of human TB worldwide, but M. africanum and M. bovis remain important agents of human disease in certain geographical regions (9). The MTBC species share identical 16S rRNA sequences, and recent studies have improved our knowledge on the genetic diversity, host range, epidemiological aspects, and differences in pathogenicity and virulence among the species of the complex (10,11).…”

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Multidrug-Resistant Mycobacterium tuberculosis of the Latin American Mediterranean Lineage, Wrongly Identified as Mycobacterium pinnipedii (Spoligotype International Type 863 [SIT863]), Causing Active Tuberculosis in South Brazil

et al. 2015

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We recently detected the spoligotype patterns of strains of Mycobacterium pinnipedii, a species of the Mycobacterium tuberculosis complex, in sputum samples from nine cases with pulmonary tuberculosis residing in Porto Alegre, South Brazil. Because this species is rarely encountered in humans, we further characterized these nine isolates by additional genotyping techniques, including 24-locus mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) typing, verification of the loci TbD1, RD9, pks15/1, RD Rio , and fbpC, the insertion of IS6110 at a site specific to the M. tuberculosis Latin American Mediterranean (LAM) lineage, and whole-genome sequencing. The combined analysis of these markers revealed that the isolates are in fact M. tuberculosis and more specifically belong to the LAM genotype. Most of these isolates (n ‫؍‬ 8) were shown to be multidrug resistant (MDR), which prompted us to perform partial sequencing of the rpoA, rpoB, rpoC, katG, and inhA genes. Seven isolates (77.8%) carried the S315T mutation in katG, and one of these (11%) also presented the C(؊17)T single-nucleotide polymorphism (SNP) in inhA. Interestingly, six of the MDR isolates also presented an undescribed insertion of 12 nucleotides (CCA GAA CAA CCC) in codon 516 of rpoB. No putative compensatory mutation was found in either rpoA or rpoC. This is the first report of an M. tuberculosis LAM family strain with a convergent M. pinnipedii spoligotype. These spoligotypes are observed in genotype databases at a modest frequency, highlighting that care must be taken when identifying isolates in the M. tuberculosis complex on the basis of single genetic markers. M. tuberculosis is the predominant cause of human TB worldwide, but M. africanum and M. bovis remain important agents of human disease in certain geographical regions (9). The MTBC species share identical 16S rRNA sequences, and recent studies have improved our knowledge on the genetic diversity, host range, epidemiological aspects, and differences in pathogenicity and virulence among the species of the complex (10, 11). Based on the various genotyping techniques, like spoligotyping (12), restriction fragment length polymorphism (RFLP) (13), mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) typing (14), and whole-genome sequencing (15), M. tuberculosis strains have been subdivided into lineages and families. The most geographically widespread family worldwide (spoligotyping) is the Latin American Mediterranean (LAM) lineage, which is part of the heterogeneous Euro-American lineage, one of seven M. tuberculosis lineages (16). The LAM family strains are widespread across all five continents, with a marked incidence in

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Multidrug-Resistant Mycobacterium tuberculosis of the Latin American Mediterranean Lineage, Wrongly Identified as Mycobacterium pinnipedii (Spoligotype International Type 863 [SIT863]), Causing Active Tuberculosis in South Brazil

et al. 2015

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“…2014. 44: 1387-1398 TB is caused by two distinct strains Mycobacterium africanum (Maf) and Mycobacterium tuberculosis (Mtb), with Maf causing up to half of all TB [2]. In The Gambia, TB patients infected with Maf West African type 2 are more likely to be older, HIV coinfected, and/or severely malnourished [3].…”

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Differences in T‐cell responses between Mycobacterium tuberculosis and Mycobacterium africanum‐infected patients

et al. 2014

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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 derivativespecific 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 Mtbcompared 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. Keywords: Cytokines r Mycobacterium africanum r Mycobacterium tuberculosis r T cells r TuberculosisAdditional supporting information may be found in the online version of this article at the publisher's web-site 1388 Leopold D. Tientcheu et al. Eur. J. Immunol. 2014. 44: 1387-1398 TB is caused by two distinct strains Mycobacterium africanum (Maf) and Mycobacterium tuberculosis (Mtb), with Maf causing up to half of all TB [2]. In The Gambia, TB patients infected with Maf West African type 2 are more likely to be older, HIV coinfected, and/or severely malnourished [3]. In addition, their exposed household contacts have a slower rate of progression to active disease compared with their Mtb-exposed counterparts [4], suggesting that Maf might be the less virulent of the two prevalent strains [5,6]. The heterogeneity in chest x-rays, bacillary load in sputum and clinical symptoms, likely reflects the variation in host immune response to the invading pathogen, and/or the differences between the lineages within the MTBC. For instance, Maf has slower growth in culture medium compared with Mtb [6,7], which may influence progression to active disease [4].The recently published genome of Maf reveals a high content of pseudogenes and the presence of a unique sequence -the region of difference 900 "RD900" that has been deleted evolutionarily from Mtb and M. bovis strains [8]. Many studies have concentrated on the pathogen strain differences in various geographical locations, with only a few anal...

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“…Lyophilized PCR reagents are provided that are stable at ambient temperatures, removing the need for cold chain storage. The assay targets specific sequences in the MTBC genomes and has a broad detection profile covering clinically relevant strains and subtypes; these include M. tuberculosis, Mycobacterium bovis, and Mycobacterium africanum, as all three species are clinically significant human pathogens (7,8). Two regions of the MTBC genomes are targeted: a short repetitive region, REP13E12 (9,10), and an 81-bp core region of rpoB, which encodes the ␤-subunit of RNA polymerase.…”

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Point-of-Care System for Detection of Mycobacterium tuberculosis and Rifampin Resistance in Sputum Samples

et al. 2014

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Early detection of Mycobacterium tuberculosis complex (MTBC) and markers conveying drug resistance can have a beneficial impact on preventive public health actions. We describe here a new molecular point-of-care (POC) system, the Genedrive, which is based on simple sample preparation combined with PCR to detect MTBC and simultaneously detect mutation markers in the rpoB gene directly from raw sputum sample. Hybridization probes were used to detect the presence of the key mutations in codons 516, 526, and 531 of the rpoB gene. The sensitivities for MTBC and rpoB detection from sputum samples were assessed using model samples spiked with known numbers of bacteria prepared from liquid cultures of M. tuberculosis. The overall sensitivities were 90.8% (95% confidence interval [CI], 81, 96.5) for MTBC detection and 72.3% (95% CI, 59.8, 82.7) for rpoB detection. For samples containing >1,000 CFU/ml, the sensitivities were 100% for MTBC and 85.7% for rpoB detection, while for samples containing <100 CFU/ml, the sensitivities were 86.4% and 65.9% for MTBC and rpoB detection, respectively. The specificity was shown to be 100% (95% CI, 83.2, 100) for MTBC and rpoB. The clinical sputum samples were processed using the same protocol and showed good concordance with the data generated from the model. Tuberculosis-infected subjects with smear samples assessed as scanty or negative were detectable by the Genedrive system. In these paucibacillary patients, the performance of the Genedrive system was comparable to that of the GeneXpert assay. The characteristics of the Genedrive platform make it particularly useful for detecting MTBC and rifampin resistance in low-resource settings and for reducing the burden of tuberculosis disease.

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Mycobacterium africanum—Review of an Important Cause of Human Tuberculosis in West Africa

Cited by 249 publications

References 54 publications

Multidrug-Resistant Mycobacterium tuberculosis of the Latin American Mediterranean Lineage, Wrongly Identified as Mycobacterium pinnipedii (Spoligotype International Type 863 [SIT863]), Causing Active Tuberculosis in South Brazil

Multidrug-Resistant Mycobacterium tuberculosis of the Latin American Mediterranean Lineage, Wrongly Identified as Mycobacterium pinnipedii (Spoligotype International Type 863 [SIT863]), Causing Active Tuberculosis in South Brazil

Differences in T‐cell responses between Mycobacterium tuberculosis and Mycobacterium africanum‐infected patients

Point-of-Care System for Detection of Mycobacterium tuberculosis and Rifampin Resistance in Sputum Samples

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