Sensitive lipid biomarker detection for tuberculosis in late Neanderthal skeletons from Subalyuk Cave, Hungary

Oona Y-C Lee; Houdini H T Wu; Gurdyal S Besra; David E Minnikin; Heidi Y Jaeger; Frank Maixner; Albert Zink; Mihály Gasparik; Ildikó Pap; Zsolt Bereczki; György Pálfi

doi:10.1016/j.tube.2023.102420

Sensitive lipid biomarker detection for tuberculosis in late Neanderthal skeletons from Subalyuk Cave, Hungary

Oona Y-C Lee, Houdini H T Wu, Gurdyal S Besra^*, David E Minnikin, Heidi Y Jaeger, Frank Maixner, Albert Zink, Mihály Gasparik, Ildikó Pap, Zsolt Bereczki, György Pálfi

^*Corresponding author for this work

Biosciences

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Abstract

Skeletal remains of two Neanderthal individuals, a 25-35 year-old woman and a 3-4 year-old child, were discovered in a Subalyuk Cave in North-Eastern Hungary. Radiocarbon dating of the female and child remains revealed an age of 39,732-39,076 and 36,117-35,387 cal BP, respectively. Paleopathological studies of these Neanderthal remains revealed probable evidence of skeletal mycobacterial infection, including in the sacrum of the adult specimen and the endocranial surface of the child's skull. Application of PCR amplification to the juvenile cranium and a vertebra gave a positive result (IS6110) for tuberculosis, backed up by spoligotyping. Lipid biomarker analyses of the same two specimens revealed definitive signals for C₃₂ mycoserosates, a very characteristic component of the Mycobacterium tuberculosis complex (MTBC). A vertebra from the adult provided weak evidence for mycocerosate biomarkers. The correlation of probable skeletal lesions with characteristic amplified DNA fragments and a proven lipid biomarker points to the presence of tuberculosis in these Neanderthals. In particular, the closely similar biomarker profiles, for two distinct juvenile cranial and vertebral bones, strengthen this diagnosis.

Original language	English
Article number	102420
Number of pages	8
Journal	Tuberculosis
Volume	143
Issue number	Supplement
Early online date	25 Nov 2023
DOIs	https://doi.org/10.1016/j.tube.2023.102420
Publication status	Published - Dec 2023

Bibliographical note

Acknowledgements:
We are grateful to Gareth Llewellyn and Christopher M Williams (EPSRC UK National Mass Spectrometry Facility, Swansea, UK) for providing access to their NICI-GCMS. Leverhulme Trust Project Grant F/00094/BL supported lipid biomarker detection. GSB acknowledges a Personal Research Chair from James Bardrick and a UK Medical Research Council Programme Grant MR/S000542. This project and this publication were also supported by the National Research, Development and Innovation Office (Hungary) (Grant agreement n° K 125561, ‘Tuberculosis and evolution’).

Copyright:
© 2023 The Authors.

Keywords

Adult
Child
Humans
Female
Child, Preschool
Animals
Neanderthals/genetics
Hungary
Mycobacterium tuberculosis/genetics
DNA, Bacterial/genetics
Tuberculosis/diagnosis
Skeleton/chemistry
Biomarkers/analysis
Lipids/analysis

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.tube.2023.102420Licence: Creative Commons: Attribution (CC BY)

LeeO2023SensitiveFinal published version, 4.8 MBLicence: Creative Commons: Attribution (CC BY)

1 Finished
1 Active

The Mycobacterium tuberculosis Cell Envelope: unravelling complex cell wall assembly, degradation and re-cycling pathways
Besra, D., Bhatt, A., Futterer, K., Alderwick, L. & Zhang, J.
Medical Research Council
1/03/19 → 28/02/25
Project: Research Councils
Lipid, sugar and protein biomarkers for ancient tuberculosis and leprosy
Besra, D., Minnikin, D., Cooper, H. & Viant, M.
Leverhulme Trust
1/01/11 → 30/09/14
Project: Research

Cite this

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title = "Sensitive lipid biomarker detection for tuberculosis in late Neanderthal skeletons from Subalyuk Cave, Hungary",

abstract = "Skeletal remains of two Neanderthal individuals, a 25-35 year-old woman and a 3-4 year-old child, were discovered in a Subalyuk Cave in North-Eastern Hungary. Radiocarbon dating of the female and child remains revealed an age of 39,732-39,076 and 36,117-35,387 cal BP, respectively. Paleopathological studies of these Neanderthal remains revealed probable evidence of skeletal mycobacterial infection, including in the sacrum of the adult specimen and the endocranial surface of the child's skull. Application of PCR amplification to the juvenile cranium and a vertebra gave a positive result (IS6110) for tuberculosis, backed up by spoligotyping. Lipid biomarker analyses of the same two specimens revealed definitive signals for C32 mycoserosates, a very characteristic component of the Mycobacterium tuberculosis complex (MTBC). A vertebra from the adult provided weak evidence for mycocerosate biomarkers. The correlation of probable skeletal lesions with characteristic amplified DNA fragments and a proven lipid biomarker points to the presence of tuberculosis in these Neanderthals. In particular, the closely similar biomarker profiles, for two distinct juvenile cranial and vertebral bones, strengthen this diagnosis. ",

keywords = "Adult, Child, Humans, Female, Child, Preschool, Animals, Neanderthals/genetics, Hungary, Mycobacterium tuberculosis/genetics, DNA, Bacterial/genetics, Tuberculosis/diagnosis, Skeleton/chemistry, Biomarkers/analysis, Lipids/analysis",

author = "Lee, {Oona Y-C} and Wu, {Houdini H T} and Besra, {Gurdyal S} and Minnikin, {David E} and Jaeger, {Heidi Y} and Frank Maixner and Albert Zink and Mih{\'a}ly Gasparik and Ildik{\'o} Pap and Zsolt Bereczki and Gy{\"o}rgy P{\'a}lfi",

note = "Acknowledgements: We are grateful to Gareth Llewellyn and Christopher M Williams (EPSRC UK National Mass Spectrometry Facility, Swansea, UK) for providing access to their NICI-GCMS. Leverhulme Trust Project Grant F/00094/BL supported lipid biomarker detection. GSB acknowledges a Personal Research Chair from James Bardrick and a UK Medical Research Council Programme Grant MR/S000542. This project and this publication were also supported by the National Research, Development and Innovation Office (Hungary) (Grant agreement n° K 125561, {\textquoteleft}Tuberculosis and evolution{\textquoteright}). Copyright: {\textcopyright} 2023 The Authors. ",

year = "2023",

month = dec,

doi = "10.1016/j.tube.2023.102420",

language = "English",

volume = "143",

journal = "Tuberculosis",

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T1 - Sensitive lipid biomarker detection for tuberculosis in late Neanderthal skeletons from Subalyuk Cave, Hungary

AU - Lee, Oona Y-C

AU - Wu, Houdini H T

AU - Besra, Gurdyal S

AU - Minnikin, David E

AU - Jaeger, Heidi Y

AU - Maixner, Frank

AU - Zink, Albert

AU - Gasparik, Mihály

AU - Pap, Ildikó

AU - Bereczki, Zsolt

AU - Pálfi, György

N1 - Acknowledgements: We are grateful to Gareth Llewellyn and Christopher M Williams (EPSRC UK National Mass Spectrometry Facility, Swansea, UK) for providing access to their NICI-GCMS. Leverhulme Trust Project Grant F/00094/BL supported lipid biomarker detection. GSB acknowledges a Personal Research Chair from James Bardrick and a UK Medical Research Council Programme Grant MR/S000542. This project and this publication were also supported by the National Research, Development and Innovation Office (Hungary) (Grant agreement n° K 125561, ‘Tuberculosis and evolution’). Copyright: © 2023 The Authors.

PY - 2023/12

Y1 - 2023/12

N2 - Skeletal remains of two Neanderthal individuals, a 25-35 year-old woman and a 3-4 year-old child, were discovered in a Subalyuk Cave in North-Eastern Hungary. Radiocarbon dating of the female and child remains revealed an age of 39,732-39,076 and 36,117-35,387 cal BP, respectively. Paleopathological studies of these Neanderthal remains revealed probable evidence of skeletal mycobacterial infection, including in the sacrum of the adult specimen and the endocranial surface of the child's skull. Application of PCR amplification to the juvenile cranium and a vertebra gave a positive result (IS6110) for tuberculosis, backed up by spoligotyping. Lipid biomarker analyses of the same two specimens revealed definitive signals for C32 mycoserosates, a very characteristic component of the Mycobacterium tuberculosis complex (MTBC). A vertebra from the adult provided weak evidence for mycocerosate biomarkers. The correlation of probable skeletal lesions with characteristic amplified DNA fragments and a proven lipid biomarker points to the presence of tuberculosis in these Neanderthals. In particular, the closely similar biomarker profiles, for two distinct juvenile cranial and vertebral bones, strengthen this diagnosis.

AB - Skeletal remains of two Neanderthal individuals, a 25-35 year-old woman and a 3-4 year-old child, were discovered in a Subalyuk Cave in North-Eastern Hungary. Radiocarbon dating of the female and child remains revealed an age of 39,732-39,076 and 36,117-35,387 cal BP, respectively. Paleopathological studies of these Neanderthal remains revealed probable evidence of skeletal mycobacterial infection, including in the sacrum of the adult specimen and the endocranial surface of the child's skull. Application of PCR amplification to the juvenile cranium and a vertebra gave a positive result (IS6110) for tuberculosis, backed up by spoligotyping. Lipid biomarker analyses of the same two specimens revealed definitive signals for C32 mycoserosates, a very characteristic component of the Mycobacterium tuberculosis complex (MTBC). A vertebra from the adult provided weak evidence for mycocerosate biomarkers. The correlation of probable skeletal lesions with characteristic amplified DNA fragments and a proven lipid biomarker points to the presence of tuberculosis in these Neanderthals. In particular, the closely similar biomarker profiles, for two distinct juvenile cranial and vertebral bones, strengthen this diagnosis.

KW - Adult

KW - Child

KW - Humans

KW - Female

KW - Child, Preschool

KW - Animals

KW - Neanderthals/genetics

KW - Hungary

KW - Mycobacterium tuberculosis/genetics

KW - DNA, Bacterial/genetics

KW - Tuberculosis/diagnosis

KW - Skeleton/chemistry

KW - Biomarkers/analysis

KW - Lipids/analysis

U2 - 10.1016/j.tube.2023.102420

DO - 10.1016/j.tube.2023.102420

M3 - Review article

C2 - 38012927

SN - 1472-9792

VL - 143

JO - Tuberculosis

JF - Tuberculosis

IS - Supplement

M1 - 102420

ER -

Sensitive lipid biomarker detection for tuberculosis in late Neanderthal skeletons from Subalyuk Cave, Hungary

Abstract

Bibliographical note

Keywords

UN SDGs

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Projects

The Mycobacterium tuberculosis Cell Envelope: unravelling complex cell wall assembly, degradation and re-cycling pathways

Lipid, sugar and protein biomarkers for ancient tuberculosis and leprosy

Cite this