Detection and Molecular Characterization of 9000-Year-Old Mycobacterium tuberculosis from a Neolithic Settlement in the Eastern Mediterranean

Hershkovitz, Israel; Donoghue, Helen D.; Minnikin, David E.; Besra, Gurdyal S.; Lee, Oona Y-C.; Gernaey, Angela M.; Galili, Ehud; Eshed, Vered; Greenblatt, Charles L.; Lemma, Eshetu; Bar-Gal, Gila Kahila; Spigelman, Mark
October 2008
PLoS ONE;2008, Vol. 3 Issue 10, p1
Academic Journal
Background: Mycobacterium tuberculosis is the principal etiologic agent of human tuberculosis. It has no environmental reservoir and is believed to have co-evolved with its host over millennia. This is supported by skeletal evidence of the disease in early humans, and inferred from M. tuberculosis genomic analysis. Direct examination of ancient human remains for M. tuberculosis biomarkers should aid our understanding of the nature of prehistoric tuberculosis and the host/pathogen relationship. Methodology/Principal Findings: We used conventional PCR to examine bone samples with typical tuberculosis lesions from a woman and infant, who were buried together in the now submerged site of Atlit-Yam in the Eastern Mediterranean, dating from 9250-8160 years ago. Rigorous precautions were taken to prevent contamination, and independent centers were used to confirm authenticity of findings. DNA from five M tuberculosis genetic loci was detected and had characteristics consistent with extant genetic lineages. High performance liquid chromatography was used as an independent method of verification and it directly detected mycolic acid lipid biomarkers, specific for the M. tuberculosis complex. Conclusions/Significance: Human tuberculosis was confirmed by morphological and molecular methods in a population living in one of the first villages with evidence of agriculture and animal domestication. The widespread use of animals was not a source of infection but may have supported a denser human population that facilitated transmission of the tubercle bacillus. The similarity of the M. tuberculosis genetic signature with those of today gives support to the theory of a long-term co-existence of host and pathogen.


Related Articles

  • Mycobacterial virulence and specialized secretion: same story, different ending. Behr, Marcel A.; Sherman, David R. // Nature Medicine;Mar2007, Vol. 13 Issue 3, p286 

    The article investigates the virulence and specialized secretions of Mycobacterium tuberculosis. The genomic region lost during the attenuation of Bacillus Calmette-Guérin (BCG) vaccine encodes a newly discovered secretion system conserved among gram-positive bacteria. Several studies have...

  • Mycobacterium tuberculosis virulence: lipids inside and out. Ehrt, Sabine; Schnappinger, Dirk // Nature Medicine;Mar2007, Vol. 13 Issue 3, p284 

    The article examines the role of pathogen-derived lipids on the virulence of Mycobactrium tuberculosis by researchers from New York City. During infections, M. tuberculosis has to acquire nutrients and resist host defense. The pathogen achieves this by using host-derived lipids as food, while...

  • Mycobacterium Tuberculosis-Specific TNF-α Is a Potential Biomarker for the Rapid Diagnosis of Active Tuberculosis Disease in Chinese Population. Wang, Feng; Hou, Hongyan; Xu, Lingqing; Jane, Munanie; Peng, Jing; Lu, Yanjun; Zhu, Yaowu; Sun, Ziyong // PLoS ONE;Nov2013, Vol. 8 Issue 11, p1 

    Interferon-gamma release assays (IGRAs) have proven to be useful to accurately detect Mycobacterium tuberculosis (Mtb) infection, but they cannot reliably discriminate between active tuberculosis (TB) and latent tuberculosis infection (LTBI). This study aims to test whether Mtb-specific tumor...

  • The survival kit of Mycobacterium tuberculosis. Warner, Digby F.; Mizrahi, Valerie // Nature Medicine;Mar2007, Vol. 13 Issue 3, p282 

    The article investigates the mechanisms used by Mycobacterium tuberculosis to survive within the host macrophage. Persistence of M. tuberculosis in humans depends on its ability to survive within the host macrophage. Macrophages are phagocytes at the frontline of host immune defense against...

  • Selection and Application of ssDNA Aptamers to Detect Active TB from Sputum Samples. Rotherham, Lia S.; Maserumule, Charlotte; Dheda, Keertan; Theron, Jacques; Khati, Makobetsa // PLoS ONE;Oct2012, Vol. 7 Issue 10, Special section p1 

    Background: Despite the enormous global burden of tuberculosis (TB), conventional approaches to diagnosis continue to rely on tests that have major drawbacks. The improvement of TB diagnostics relies, not only on good biomarkers, but also upon accurate detection methodologies. The 10-kDa culture...

  • Immune Responses to ESAT-6 and CFP-10 by FASCIA and Multiplex Technology for Diagnosis of M. tuberculosis Infection; IP-10 Is a Promising Marker. Borgström, Emilie; Andersen, Peter; Atterfelt, Fredrik; Julander, Inger; Källenius, Gunilla; Maeurer, Markus; Rosenkrands, Ida; Widfeldt, Maria; Bruchfeld, Judith; Gaines, Hans // PLoS ONE;Nov2012, Vol. 7 Issue 11, Special section p1 

    Background: There is a need for reliable markers to diagnose active and latent tuberculosis (TB). The interferon gamma release assays (IGRAs) are compared to the tuberculin skin test (TST) more specific, but cannot discriminate between recent or remote TB infection. Here the Flow-cytometric...

  • Host Cytokine Responses Induced after Overnight Stimulation with Novel M. tuberculosis Infection Phase-Dependent Antigens Show Promise as Diagnostic Candidates for TB Disease. Essone, Paulin N.; Chegou, Novel N.; Loxton, Andre G.; Stanley, Kim; Kriel, Magdalena; van der Spuy, Gian; Franken, Kees L.; Ottenhoff, Tom H.; Walzl, Gerhard // PLoS ONE;Jul2014, Vol. 9 Issue 7, p1 

    Background: We previously identified Mycobacterium tuberculosis (M.tb) antigen-induced host markers that showed promise as TB diagnostic candidates in 7-day whole blood culture supernatants. The aim of the present study was to evaluate the utility of these markers further, and cross-compare...

  • Circulating B-Lymphocytes as Potential Biomarkers of Tuberculosis Infection Activity. Sebina, Ismail; Biraro, Irene A.; Dockrell, Hazel M.; Elliott, Alison M.; Cose, Stephen // PLoS ONE;Sep2014, Vol. 9 Issue 9, p1 

    Accurate biomarkers of Mycobacterium tuberculosis infection activity would significantly improve early diagnosis, treatment and management of M. tuberculosis infection. We hypothesised that circulating B-lymphocytes may be useful biomarkers of tuberculosis (TB) infection status in highly...

  • Use of the VNTR typing technique to determine the origin of Mycobacterium tuberculosis strains isolated from Filipino patients in Korea. Lee, Jihye; Tupasi, Thelma; Park, Young // World Journal of Microbiology & Biotechnology;May2014, Vol. 30 Issue 5, p1625 

    With increasing international interchange of personnel, international monitoring is necessary to decrease tuberculosis incidence in the world. This study aims to develop a new tool to determine origin of Mycobacterium tuberculosis strains isolated from Filipino patients living in Korea....


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics