Genomic characterization of Mycobacterium tuberculosis lineage 7 and a proposed name: ‘Aethiops vetus’

Nebenzahl-Guimaraes, Hanna; Yimer, Solomon Abebe; Holm‐Hansen, Carol; Beer, Jessica de; Brosch, Roland; Soolingen, Dick van

doi:10.1099/mgen.0.000063

Cited by 27 publications

(22 citation statements)

References 27 publications

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“…M. tuberculosis strains show substantial variation in their virulence and immunogenicity, which ultimately impact their propensity to induce or accelerate active disease (14)(15)(16)(17). Based on whole-genome sequence analysis, human-adapted M. tuberculosis complex strains have been divided into seven phylogenetic lineages (15)(16)(17)(18)(19)(20). Lineages 2 to 4, which harbor a deletion in the genomic region known as TbD1, are collectively referred to as "modern" because these strains diversified genetically more recently than the "ancient" lineages (lineages 1, 5, and 6) and "intermediate" lineage 7 (17,18,21).…”

Section: Bacterial Pathogenesis and Immune Response Pathogenesis Of Imentioning

confidence: 99%

Incipient and Subclinical Tuberculosis: a Clinical Review of Early Stages and Progression of Infection

et al. 2018

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SUMMARYTuberculosis (TB) is the leading infectious cause of mortality worldwide, due in part to a limited understanding of its clinical pathogenic spectrum of infection and disease. Historically, scientific research, diagnostic testing, and drug treatment have focused on addressing one of two disease states: latent TB infection or active TB disease. Recent research has clearly demonstrated that human TB infection, from latent infection to active disease, exists within a continuous spectrum of metabolic bacterial activity and antagonistic immunological responses. This revised understanding leads us to propose two additional clinical states: incipient and subclinical TB. The recognition of incipient and subclinical TB, which helps divide latent and active TB along the clinical disease spectrum, provides opportunities for the development of diagnostic and therapeutic interventions to prevent progression to active TB disease and transmission of TB bacilli. In this report, we review the current understanding of the pathogenesis, immunology, clinical epidemiology, diagnosis, treatment, and prevention of both incipient and subclinical TB, two emerging clinical states of an ancient bacterium.

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Section: Bacterial Pathogenesis and Immune Response Pathogenesis Of Imentioning

confidence: 99%

Incipient and Subclinical Tuberculosis: a Clinical Review of Early Stages and Progression of Infection

et al. 2018

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“…Understanding the molecular epidemiology of TB is important for regional disease control. For instance, distinct strains may be linked to outbreaks [10], high virulence [42], emergency of drug resistance [44], disease progression [43], and can point to the geographic origin of a strain [20,33] as well as identify new lineages [17,28].…”

Section: Introductionmentioning

confidence: 99%

“…We are aware of only very few Ethiopian studies using spoligotyping and MIRU-VNTR simultaneously to profile MTBC strains [1,9,36,37,43]. New lineages such as the MTBC lineage lineage_7/Aethiops vertus [17,28], Ethiopia_2 and Ethiopia_3 [37] were newly assigned. Most surveys were in geographic areas more accessible than South Omo.…”

Section: Introductionmentioning

confidence: 99%

Molecular epidemiology of clinical Mycobacterium tuberculosis complex isolates in South Omo, Southern Ethiopia

et al. 2020

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Background Tuberculosis (TB) is caused by Mycobacterium tuberculosis complex (MTBC). Mapping the genetic diversity of MTBC in high TB burden country like Ethiopia is important to understand principles of the disease transmission and to strengthen the regional TB control program. The aim of this study was to investigate the genetic diversity of Mycobacterium tuberculosis complex (MTBC) isolates circulating in the South Omo, southern Ethiopia. Methods MTBC isolates (N = 156) were genetically analyzed using spacer oligotyping (spoligotyping) and mycobacterial interspersed repetitive unit-variable number of tandem repeat (MIRU-VNTR) typing. Major lineages and lineages were identified using MTBC databases. Logistic regression was used to correlate patient characteristics with strain clustering. Results The study identified Euro-American (EA), East-African-Indian (EAI), Indo-Oceanic (IO), Lineage_7/Aethiops vertus, Mycobacterium bovis and Mycobacterium africanum major lineages in proportions of 67.3% (105/156), 22.4% (35/156), 6.4% (10/156), 1.9% (3/156), 1.3% (2/156) and 0.6% (1/156), respectively. Lineages identified were Delhi/CAS 23.9% (37/155), Ethiopia_2 20.6% (32/155), Haarlem 14.2% (22/155), URAL 14.2%(22/155), Ethiopia_3 8.4% (13/155), TUR 6.5% (10/155), Lineage_7/Aethiops vertus 1.9% (3/155), Bovis 1.3% (2/155), LAM 1.3% (2/155), EAI 0.6% (1/155), X 0.6% (1/155) and Ethiopia H37Rv-like strain 0.6% (1/155). Of the genotyped isolates 5.8% (9/155) remained unassigned. The recent transmission index (RTI) was 3.9%. Orphan strains compared to shared types (AOR: 0.09, 95% CI: 0.04–0.25) were associated with reduced odds of clustering. The dominant TB lineage in pastoral areas was EAI and in non-pastoral areas was EA. Conclusion The epidemiological data, highly diverse MTBC strains and a low RTI in South Omo, provide information contributing to the TB Control Program of the country.

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“…The TbD1deleted (ΔTbD1) L2, L3, L4 lineages, also referred to as "modern" Mtb strains 2 , of the Beijing, CAS/Dehli and Euro-American Mtb strain families 11 are often associated with globally spread TB epidemics [12][13][14][15] , whereas TbD1-intact strains, also known as "ancestral" strains 2 of the East-African-Indian (EAI) strain family, rather represent endemic Mtb strains restricted to a given geographical area 15 . The TbD1-intact L1 strains are prevalent in South India and South East Asia 5 , while L7 strains are restricted to the region around the Horn of Africa [16][17][18] . The L1 strains can be subdivided in numerous sublineages 19,20 and can cause pulmonary TB as well as extrapulmonary TB in susceptible populations 21,22 .…”

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confidence: 99%

TbD1 deletion as a driver of the evolutionary success of modern epidemic Mycobacterium tuberculosis lineages

et al. 2020

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Mycobacterium tuberculosis (Mtb) strains are classified into different phylogenetic lineages (L), three of which (L2/L3/L4) emerged from a common progenitor after the loss of the MmpS6/MmpL6-encoding Mtb-specific deletion 1 region (TbD1). These TbD1-deleted "modern" lineages are responsible for globally-spread tuberculosis epidemics, whereas TbD1intact "ancestral" lineages tend to be restricted to specific geographical areas, such as South India and South East Asia (L1) or East Africa (L7). By constructing and characterizing a panel of recombinant TbD1-knock-in and knockout strains and comparison with clinical isolates, here we show that deletion of TbD1 confers to Mtb a significant increase in resistance to oxidative stress and hypoxia, which correlates with enhanced virulence in selected cellular, guinea pig and C3HeB/FeJ mouse infection models, the latter two mirroring in part the development of hypoxic granulomas in human disease progression. Our results suggest that loss of TbD1 at the origin of the L2/L3/L4 Mtb lineages was a key driver for their global epidemic spread and outstanding evolutionary success.

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Genomic characterization of Mycobacterium tuberculosis lineage 7 and a proposed name: ‘Aethiops vetus’

Cited by 27 publications

References 27 publications

Incipient and Subclinical Tuberculosis: a Clinical Review of Early Stages and Progression of Infection

Incipient and Subclinical Tuberculosis: a Clinical Review of Early Stages and Progression of Infection

Molecular epidemiology of clinical Mycobacterium tuberculosis complex isolates in South Omo, Southern Ethiopia

TbD1 deletion as a driver of the evolutionary success of modern epidemic Mycobacterium tuberculosis lineages

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