Pericarditis caused by Mycobacterium africanum: case report.

BACKGROUND: Mycobacterium africanum is a member of the Mycobacterium tuberculosis complex (MTBC) and is endemic in West Africa, where it causes up to half of all cases of pulmonary tuberculosis. Here, we report the first isolation of Mycobacterium africanum from the pericardial effusion culture of a patient with tuberculous pericarditis. CASE PRESENTATION: A 31-year-old man, native from Senegal, came to the emergency room with massive pericardial effusion and cardiac tamponade requiring pericardiocentesis. M. africanum subtype II was identified in the pericardial fluid. The patient completed 10 months of standard treatment, with a favorable outcome. CONCLUSIONS: We report the first case of tuberculous pericarditis caused by Mycobacterium africanum, which provide evidence that this microorganism can cause pericardial disease and must be considered in patients from endemic areas presenting with pericardial effusion.

Import and transmission of Mycobacterium orygis and Mycobacterium africanum, Norway.

BACKGROUND: The aim of the current study was to improve our understanding of the origins and transmission of Mycobacterium africanum (MAF) in Norway. METHODS: Whole-genome sequences (WGS) were generated for all (n = 29) available clinical isolates received at the Norwegian National Reference Laboratory for Mycobacteria (NRL) and identified as MAF in Norway, in the period 2010-2020. Phylogenetic analyses were performed. RESULTS: The analyses indicated several imports of MAF lineage 6 from both East and West African countries, whereas MAF lineage 5 was restricted to patients with West African connections. We also find evidence for transmission of MAF in Norway. Finally, our analyses revealed that a group of isolates from patients originating in South Asia, identified as MAF by means of a commercial line-probe assay, in fact belonged to Mycobacterium orygis. CONCLUSIONS: Most MAF cases in Norway are the result of import, but transmission is occurring within Norway.

Vacuum-assisted closure therapy of paradoxical reaction in tuberculous lymphadenopathy caused by Mycobacterium africanum.

A 26-year-old HIV-negative male from Ghana was treated for cervical, intrathoracic and abdominal lymph node tuberculosis (TB) and tuberculous hepatitis. Penetration of the thoracic trachea by a mediastinal lymph node had caused bronchomucosal TB. Sputum culture grew M. africanum, sensitive to all first-line antituberculous drugs. Four weeks after the beginning of directly observed treatment with isoniazid, rifampin, pyrazinamide and ethambutol, the right cervical lymph node increased in size, liquefied and caused a spontaneous fistula. A biopsy of the necrotized lymph node revealed rare acid-fast bacilli with a positive PCR for Mycobacterium tuberculosis complex. After debridement, vacuum-assisted closure therapy was performed for 6 weeks. Five months after the beginning of antituberculous therapy, a second paradoxical reaction occurred, with painful swelling of two contralateral supraclavicular lymph nodes. Extirpation of one node yielded a positive PCR for M. tuberculosis complex; the culture was negative. Antituberculous treatment was continued, and additional treatment with oral prednisolone 20 mg daily for 1 month tapering over 10 weeks was introduced, resulting in a decrease in lymphadenopathy. Antituberculous treatment was continued for a total of 9 months. The outcome was favorable, no further lymphadenopathy occurred over the following 6 months.

The Biology and Epidemiology of Mycobacterium africanum.

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.

Type I Interferon is Pathogenic During Chronic Mycobacterium africanum Infection.

Type I interferons (IFNs, including IFN-αß) contribute to the pathogenesis of Mycobacterium tuberculosis strains that induce high IFN-αß levels. In the current study we examined the role of IFN-αß during infection with a Mycobacterium africanum strain that induces low IFN-ß levels. We infected wild-type and IFN-αß receptor knockout mice with M. africanum and monitored bacterial growth, lung disease, and survival over 292 days. We found reduced lung bacterial burdens and less severe histopathological findings in the absence of IFN-αß signaling. We conclude that IFN-αß is pathogenic during chronic M. africanum infection and that the pathogenic effects may be mediated through poorer control of bacterial growth.

Tuberculosis Caused by Mycobacterium africanum, United States, 2004-2013.

Mycobacterium africanum is endemic to West Africa and causes tuberculosis (TB). We reviewed reported cases of TB in the United States during 2004-2013 that had lineage assigned by genotype (spoligotype and mycobacterial interspersed repetitive unit variable number tandem repeats). M. africanum caused 315 (0.4%) of 73,290 TB cases with lineage assigned by genotype. TB caused by M. africanum was associated more with persons from West Africa (adjusted odds ratio [aOR] 253.8, 95% CI 59.9-1,076.1) and US-born black persons (aOR 5.7, 95% CI 1.2-25.9) than with US-born white persons. TB caused by M. africanum did not show differences in clinical characteristics when compared with TB caused by M. tuberculosis. Clustered cases defined as >2 cases in a county with identical 24-locus mycobacterial interspersed repetitive unit genotypes, were less likely for M. africanum (aOR 0.1, 95% CI 0.1-0.4), which suggests that M. africanum is not commonly transmitted in the United States.

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

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.

Diversification of gene content in the Mycobacterium tuberculosis complex is determined by phylogenetic and ecological signatures.

We analyzed the pan-genome and gene content modulation of the most diverse genome data set of the Mycobacterium tuberculosis complex (MTBC) gathered to date. The closed pan-genome of the MTBC was characterized by reduced accessory and strain-specific genomes, compatible with its clonal nature. However, significantly fewer gene families were shared between MTBC genomes as their phylogenetic distance increased. This effect was only observed in inter-species comparisons, not within-species, which suggests that species-specific ecological characteristics are associated with changes in gene content. Gene loss, resulting from genomic deletions and pseudogenization, was found to drive the variation in gene content. This gene erosion differed among MTBC species and lineages, even within M. tuberculosis, where L2 showed more gene loss than L4. We also show that phylogenetic proximity is not always a good proxy for gene content relatedness in the MTBC, as the gene repertoire of Mycobacterium africanum L6 deviated from its expected phylogenetic niche conservatism. Gene disruptions of virulence factors, represented by pseudogene annotations, are mostly not conserved, being poor predictors of MTBC ecotypes. Each MTBC ecotype carries its own accessory genome, likely influenced by distinct selective pressures such as host and geography. It is important to investigate how gene loss confer new adaptive traits to MTBC strains; the detected heterogeneous gene loss poses a significant challenge in elucidating genetic factors responsible for the diverse phenotypes observed in the MTBC. By detailing specific gene losses, our study serves as a resource for researchers studying the MTBC phenotypes and their immune evasion strategies.IMPORTANCEIn this study, we analyzed the gene content of different ecotypes of the Mycobacterium tuberculosis complex (MTBC), the pathogens of tuberculosis. We found that changes in their gene content are associated with their ecological features, such as host preference. Gene loss was identified as the primary driver of these changes, which can vary even among different strains of the same ecotype. Our study also revealed that the gene content relatedness of these bacteria does not always mirror their evolutionary relationships. In addition, some genes of virulence can be variably lost among strains of the same MTBC ecotype, likely helping them to evade the immune system. Overall, our study highlights the importance of understanding how gene loss can lead to new adaptations in these bacteria and how different selective pressures may influence their genetic makeup.

Immunogenic Mycobacterium africanum strains associated with ongoing transmission in The Gambia.

In West Africa, Mycobacterium tuberculosis strains co-circulate with M. africanum, and both pathogens cause pulmonary tuberculosis in humans. Given recent findings that M. tuberculosis T-cell epitopes are hyperconserved, we hypothesized that more immunogenic strains have increased capacity to spread within the human host population. We investigated the relationship between the composition of the mycobacterial population in The Gambia, as measured by spoligotype analysis, and the immunogenicity of these strains as measured by purified protein derivative-induced interferon-γ release in ELISPOT assays of peripheral blood mononuclear cells. We found a positive correlation between strains with superior spreading capacity and their relative immunogenicity. Although our observation is true for M. tuberculosis and M. africanum strains, the association was especially pronounced in 1 M. africanum sublineage, characterized by spoligotype shared international type 181, which is responsible for 20% of all tuberculosis cases in the region and therefore poses a major public health threat in The Gambia.

Relevance of genomic diversity of Mycobacterium tuberculosis complex in Africa.

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.

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

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.

Phylogenomics of Mycobacterium africanum reveals a new lineage and a complex evolutionary history.

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.

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

OBJECTIVE: We conducted a cross-sectional study in the five administrative regions of Northern Ghana to determine the diversity of Mycobacterium tuberculosis complex (MTBC) sub/lineages and their susceptibility to isoniazid (INH) and rifampicin (RIF). METHODS: Sputum specimens were collected and cultured from 566 pulmonary tuberculosis patients reporting to 17 health facilities from 2015 to 2019. Mycobacterial isolates obtained from solid cultures were confirmed as members of the MTBC by PCR amplification of IS6110 and rpoß and assigned lineages and sub-lineages using spoligotyping. RESULTS: Of 294 mycobacterial isolates recovered, MTBC species identified were: M. tuberculosis sensu stricto (Mtbss) 241 (82.0%), M. africanum 41 (13.9%) and M. bovis four (1.4%) with eight (2.7%) unidentified. The human-adapted lineages (L) identified (N=279) were L1 (8/279, 2.9%), L2 (15/279, 5.4%), L3 (7/279, 2.5%), L4 (208/279, 74.5%), L5 (13/279, 4.7%) and L6 (28/279, 10.0%) with three unidentified lineages. Among the 208 L4, the dominant sub-lineages in the region were the Cameroon 120/208 (57.7%) and Ghana 50/208 (24.0%). We found 4.4% (13/294) and 0.7% (2/294) of the patients infected with MTBC isolates resistant to INH only and RIF only, respectively, with 2.4% (7/294) being infected with MDR strains. Whereas L6 was associated with the elderly, we identified that the Ghana sub-lineage of L4 was associated with both INH and MDR (p<0.05), making them important TB pathogens in Northern Ghana and a growing public health concern.

Bacterial Load Comparison of the Three Main Lineages of Mycobacterium tuberculosis Complex in West Africa.

Studies have shown an association between bacterial load and virulence; however, not much is known about the diversity in this phenotypic characteristic of Mycobacterium tuberculosis complex (MTBC). This study was therefore aimed to determine the differences in bacterial load of the three most prevalent MTBC genotypes (L4, L5, and L6) in West Africa at the time of diagnosis. A total of 170 paired fresh sputum samples were collected; one part in guanidinium thiocyanate (GTC) was used for RNA extraction and tuberculosis molecular bacterial load assay (TB-MBLA), and the other part without GTC was confirmed for TB positivity using GeneXpert MTB/RIF, smear microscopy grading, and culture on Löwenstein-Jensen media slants. The 170 sputum samples comprised 155 new cases, three follow-up cases, and 12 TB negative sputum samples. The time-to-culture positivity (TTP) and degree of culture positivity (DCP) were recorded. All 122 isolates obtained were spoligotyped for lineage (L) classification, but spoligotypes were obtained from 120 isolates. Of the typed isolates, 70.0, 10.8, 10.8, 4.2, 2.5, 0.8, and 0.8% were lineages 4, 5, 6, 2, 3, 1, and Mycobacterium bovis, respectively. Further analysis of the three most prevalent lineages showed significantly shorter TTP and higher DCP by L4 compared to L5 and L6, respectively: TTP 20.8, vs. 26.5, and 28.2 days; p-value = 0.005 and DCP 1.27, vs. 0.81 and 0.29, p < 0.001. The average TB-MBLA measured bacterial load of L4 was 3.82 Log10eCFU/ml which was not significantly different from 3.81 and 3.80 Log10eCFU/ml of L5 and L6, respectively, p = 0.84. Degrees of smear microscopy L4 = 1.20, L5 = 1.20, and L6 = 0.92 and GeneXpert Cq values L4 = 17.08, L5 = 18.37, and L6 = 17.59 showed no significant difference between the lineages, p = 0.72 and p = 0.48, respectively. Retrospective analysis of a larger sample confirmed the difference in TTP, p < 0.001. In conclusion, the observed shorter TTP and high DCP of L4 could signify high growth rate in culture that is independent of total bacterial load at diagnosis.

Genomic epidemiological analysis identifies high relapse among individuals with recurring tuberculosis and provides evidence of recent household-related transmission of tuberculosis in Ghana.

OBJECTIVE: To retrospectively investigate the cause of recurring tuberculosis (rcTB) among participants with pulmonary TB recruited from a prospective population-based study conducted between July 2012 and December 2015. METHODS: Mycobacterium tuberculosis complex isolates obtained from rcTB cases were characterized by standard mycobacterial genotyping tools, whole-genome sequencing, and phylogenetic analysis carried out to assess strain relatedness. RESULTS: The majority (58.3%, 21/36) of study participants with rcTB episodes had TB recurrence within 12 months post treatment. TB strains with isoniazid (INH) resistance were found in 19.4% (7/36) of participants at the primary episode, of which 29% (2/7) were also rifampicin-resistant. On TB recurrence, an INH-resistant strain was found in a larger proportion of participants, 27.8% (10/36), of which 40% (4/10) were MDR-TB strains. rcTB was attributed to relapse (same strain) in 75.0% (27/36) of participants and 25.0% (9/36) to re-infection. CONCLUSION: Our findings indicate that previous unresolved infectiondue to inadequate treatment, may be the major cause of rcTB.

The Relevance of Genomic Epidemiology for Control of Tuberculosis in West Africa.

Tuberculosis (TB), an airborne infectious disease caused by Mycobacterium tuberculosis complex (MTBC), remains a global health problem. West Africa has a unique epidemiology of TB that is characterized by medium- to high-prevalence. Moreover, the geographical restriction of M. africanum to the sub-region makes West Africa have an extra burden to deal with a two-in-one pathogen. The region is also burdened with low case detection, late reporting, poor treatment adherence leading to development of drug resistance and relapse. Sporadic studies conducted within the subregion report higher burden of drug resistant TB (DRTB) than previously thought. The need for more sensitive and robust tools for routine surveillance as well as to understand the mechanisms of DRTB and transmission dynamics for the design of effective control tools, cannot be overemphasized. The advancement in molecular biology tools including traditional fingerprinting and next generation sequencing (NGS) technologies offer reliable tools for genomic epidemiology. Genomic epidemiology provides in-depth insight of the nature of pathogens, circulating strains and their spread as well as prompt detection of the emergence of new strains. It also offers the opportunity to monitor treatment and evaluate interventions. Furthermore, genomic epidemiology can be used to understand potential emergence and spread of drug resistant strains and resistance mechanisms allowing the design of simple but rapid tools. In this review, we will describe the local epidemiology of MTBC, highlight past and current investigations toward understanding their biology and spread as well as discuss the relevance of genomic epidemiology studies to TB control in West Africa.

Comparative genomics shows differences in the electron transport and carbon metabolic pathways of Mycobacterium africanum relative to Mycobacterium tuberculosis and suggests an adaptation to low oxygen tension.

The geographically restricted Mycobacterium africanum lineages (MAF) are primarily found in West Africa, where they account for a significant proportion of tuberculosis. Despite this phenomenon, little is known about the co-evolution of these ancient lineages with West Africans. MAF and M. tuberculosis sensu stricto lineages (MTB) differ in their clinical, in vitro and in vivo characteristics for reasons not fully understood. Therefore, we compared genomes of 289 MAF and 205 MTB clinical isolates from the 6 main human-adapted M. tuberculosis complex lineages, for mutations in their Electron Transport Chain and Central Carbon Metabolic pathway in order to explain these metabolic differences. Furthermore, we determined, in silico, whether each mutation could affect the function of genes encoding enzymes in these pathways. We found more mutations with the potential to affect enzymes in these pathways in MAF lineages compared to MTB lineages. We also found that similar mutations occurred in these pathways between MAF and some MTB lineages. Generally, our findings show further differences between MAF and MTB lineages that may have contributed to the MAF clinical and growth phenotype and indicate potential adaptation of MAF lineages to a distinct ecological niche, which we suggest includes areas characterized by low oxygen tension.

Whole Genome Sequencing and Spatial Analysis Identifies Recent Tuberculosis Transmission Hotspots in Ghana.

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.

Indigenous Transmission of Mycobacterium africanum in Canada: A Case Series and Cluster Analysis.

Mycobacterium africanum is an important cause of human tuberculosis and is found almost exclusively in West Africa. We identified a cluster of patients in Montreal, Canada, with M africanum disease that share identical genotypic signatures by mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing and a putative epidemiological link, thus providing evidence of possible local transmission of M africanum in Montreal over a 10-year period.

Experimental Evidence for Limited in vivo Virulence of Mycobacterium africanum.

Tuberculosis remains a public health problem and a main cause of death to humans. Both Mycobacterium tuberculosis and Mycobacterium africanum cause tuberculosis. In contrast to M. tuberculosis, which is geographically spread, M. africanum is restricted to West Africa. Differences have also been found in the growth rate and type of disease caused by M. africanum, globally suggesting an attenuation of this bacteria. In this study, we used the mouse model of infection to follow the dynamics of M. africanum infection in terms of bacterial burdens and tissue pathology, as well as the immune response triggered. Our findings support a lower virulence of M. africanum as compared to M. tuberculosis, including in mice lacking IFN-γ, a major protective cytokine in tuberculosis. Furthermore, the lung immune response triggered by M. africanum infection in wild-type animals was characterized by a discrete influx of leukocytes and a modest transcriptional upregulation of inflammatory mediators. Our findings contribute to elucidate the pathogenesis of M. africanum, supporting the hypothesis that this is an attenuated member of the tuberculosis-causing bacteria. Understanding the biology of M. africanum and how it interacts with the host to establish infection will have implications for our knowledge of TB and for the development of novel and better tools to control this devastating disease.