10e Rencontre du Groupe d’Anthropologie et d’Archéologie Funéraire, May 23, 2018
International audienceLa léproserie médiévale Saint-Thomas d’Aizier (fouillée de 1998 à 2010) est... more International audienceLa léproserie médiévale Saint-Thomas d’Aizier (fouillée de 1998 à 2010) est située en pleine forêt de Brotonne et compte parmi les propriétés de l’abbaye de Fécamp (Normandie, France). Seule la chapelle romane, dédiée à Thomas Becket, subsiste à l’état de ruines. Petit édifice rural a priori sans importance notable, il présente l’intérêt d’être intégralement conservé et offre l’opportunité très rare d’une fouille quasi exhaustive. Fondé vers la fin du XIIe siècle et abandonné au cours du XVIe siècle, l’établissement n’est plus fréquenté ensuite que de façon sporadique. Il est progressivement gagné par la forêt, ce qui a permis une fossilisation de l’enclos et la sauvegarde des vestiges. En principe, une léproserie est un centre de soins dévolus aux seuls lépreux/ses. À Aizier, l’étude des sources historiques et archéologiques a permis de comprendre l’organisation de cet établissement, son origine, son mode de fonctionnement et son évolution dans le temps avec des ruptures par rapport à sa destination d’origine (sexe, âge, pathologies). L’analyse de la population inhumée apporte non seulement un éclairage inédit sur les conditions de vie, la structuration des espaces et la nature des défunts, mais aussi sur les soins donnés aux malades accueillis dans cette communauté pénitentielle de lépreux. En effet, la population enterrée à Aizier est particulièrement intéressante pour l’étude de la lèpre au Moyen Âge, mais aussi pour connaître la perception de cette maladie et mieux appréhender ses implications sociales et thérapeutiques
The salivary peroxidase system has been described as inhibitory, and the main product, hypothiocy... more The salivary peroxidase system has been described as inhibitory, and the main product, hypothiocyanite (OSCN -), inhibits glycolysis and oxygen uptake (Carlsson et al., 1983). However, the similar lactoperoxidase (LPO) system is known to be protective under anaerobic conditions, at least in the short term (Carlsson, 1980). In the present study, the long-term effect of the LPO system on bacterial growth and acid production was investigated, by means of experimental microbial plaque samples. Dental plaque is an open ecosystem in which bacteria grow on a surface in a microbial film and are subjected to a fluctuating nutrient supply. The behavior of organisms under these conditions is likely to differ from that of bacteria in batch or continuous cultures (Wimpenny, 1981). An artificial mouth is a laboratory microcosm which enables plaque bacteria to be grown under conditions analogous to those found in vivo. Earlier work with this type of model demonstrated that 'Streptococcus mitior' LPA-1 produced sufficient hydrogen peroxide (H202) to antagonize Streptococcus rattus (mutans) BHT in a mixed plaque on teeth, and to activate the peroxidase system when LPO was present (Donoghue et al., 1985).
Tuberculosis is a significant global disease today, so understanding its origins and history is i... more Tuberculosis is a significant global disease today, so understanding its origins and history is important. It is primarily a lung infection and is transmitted by infectious aerosols from person to person, so a high population density encourages its spread. The causative organism is Mycobacterium tuberculosis, an obligate pathogen in the M. tuberculosis complex that also contains closely related species, such as Mycobacterium bovis, that primarily infect animals. Typical bone lesions occur in about 5% of untreated infections. These can be recognized in historical and archaeological material, along with nonspecific paleopathology such as new bone formation (periostitis), especially on ribs. Based on such lesions, tuberculosis has been found in ancient Egypt, pre-Columbian America, and Neolithic Europe. The detection of M. tuberculosis ancient DNA (aDNA) by using PCR led to the development of the new field of paleomicrobiology. As a result, a large number of tuberculosis cases were rec...
The bacillus Calmette–Guérin (BCG) vaccine has been in use for prevention of tuberculosis for ove... more The bacillus Calmette–Guérin (BCG) vaccine has been in use for prevention of tuberculosis for over a century. It remains the only widely available tuberculosis vaccine and its protective efficacy has varied across geographical regions. Since it was developed, the BCG vaccine strain has been shared across different laboratories around the world, where use of differing culture methods has resulted in genetically distinct strains over time. Whilst differing BCG vaccine efficacy around the world is well documented, and the reasons for this may be multifactorial, it has been hypothesized that genetic differences in BCG vaccine strains contribute to this variation. Isolates from an historic archive of lyophilized BCG strains were regrown, DNA was extracted and then whole-genome sequenced using Oxford Nanopore Technologies. The resulting whole-genome data were plotted on a phylogenetic tree and analysed to identify the presence or absence of regions of difference (RDs) and single-nucleotid...
HAL (Le Centre pour la Communication Scientifique Directe), Aug 28, 2018
International audienceLeprosy was widespread in Mediaeval Europe but molecular evidence indicates... more International audienceLeprosy was widespread in Mediaeval Europe but molecular evidence indicates geographical differences in the Mycobacterium leprae genotypes found at different times and locations. M. leprae requires a living host, and different human populations are associated with different lineages. Data are available from the UK and Scandinavia, Central, Southern and Eastern Europe, but little is known of the molecular characteristics of leprosy from Northern France. The paleopathology of leprosy is distinctive, so enables recognition of the disease in established cases. Therefore, nasal scrapings, and samples from ribs, femurs and toes, were taken from 15 individuals with typical paleopathology at the leprosarium of Saint Thomas d’Aizier (1350-1450 CE). After grinding to a powder, samples were demineralised in EDTA/Proteinase K at 56oC, mixed on a bead beater then split into 2 aliquots. One was treated with 0.1M PTB to break any covalent cross-links then both aliquots were incubated in lysis buffer containing guanidium thiocyanate. DNA was captured by silica or precipitated from the silica supernatants. Real-time PCR was used, with primers and probes for the M. leprae repetitive sequences RLEP (37 copies/cell) and RepLep (15 copies/cell). Eleven individuals were strongly positive for M. leprae DNA, two were weakly positive and two were negative. The stronger positive samples were genotyped. Unlike M. leprae ancient DNA from central and southern Europe, these Norman strains were of genotype 3I. However, in two individuals a variant M. leprae 3I-1 type was also found that has only once been reported previously, from 800-900 years earlier. This was in a skeleton from Great Chesterfield, East Anglia, UK, dated to 600 CE. This variant appears to be intermediate between sub-type 2F and 3I
Whole genome analysis of Mycobacterium tuberculosis isolates from recurrent episodes of tuberculo... more Whole genome analysis of Mycobacterium tuberculosis isolates from recurrent episodes of tuberculosis, Finland, 1995-2013
International audienceDans l’Europe médiévale, la lèpre était une affection largement répandue. C... more International audienceDans l’Europe médiévale, la lèpre était une affection largement répandue. Cependant, des preuves moléculaires indiquent l’existence de différents génotypes du Mycobacterium leprae selon les lieux de découverte et les époques. M. leprae nécessite l’hébergement par un être vivant et diverses lignées sont associées à différentes populations humaines. Des données sont disponibles pour le Royaume-Uni, la Scandinavie, l’Europe centrale, du Sud et de l’Est, mais peu sont accessibles pour caractériser moléculairement la lèpre dans le Nord de la France. La paléopathologie de la lèpre est caractéristique et permet la reconnaissance de la maladie sur des cas établis. Des échantillons osseux montrant des signes de lèpre ont été prélevés à partir de divers sites : Lisieux (IVe – VIIe s.), Vendeuil-Caply (Ve-VIe s.), Neuville-sur-Escaut (début à milieu VIe s.) et la léproserie de Saint Thomas d’Aizier (fin XIIe-début XVIe s.). Quand cela était possible, des échantillons ont ...
To give an insight into the different manifestations of leprosy and their biological consequences... more To give an insight into the different manifestations of leprosy and their biological consequences in the Avar Age of the Hungarian Duna-Tisza Interfluve, two cases from the 7th-century-CE osteoarchaeological series of Kiskundorozsma–Daruhalom-dűlő II (Hungary; n = 94) were investigated. Based on the macromorphology of the bony changes indicative of Hansen’s disease,KD271(a middle-aged male) andKD520(a middle-aged female) represent the two extremes of leprosy.KD271appears to have an advanced-stage, long-standing near-lepromatous or lepromatous form of the disease, affecting not only the rhinomaxillary region but also both upper and lower limbs. This has led to severe deformation and disfigurement of the involved anatomical areas of the skeleton, resulting in his inability to perform the basic activities of daily living, such as eating, drinking, grasping, standing or walking. The skeleton ofKD520shows no rhinomaxillary lesions and indicates the other extreme of leprosy, a near-tuberc...
The characterisation of ancient tuberculosis is not totally dependent on the recovery of intact g... more The characterisation of ancient tuberculosis is not totally dependent on the recovery of intact genomes. Judicious combinations of ancient DNA fragments and specific lipid biomarkers provide unambiguous diagnosis and these protocols are capable of refinement and extension. Currently, there is no direct evidence for exclusive co-evolution of humans and tuberculosis. A developing body of data suggests that the initial evolution of tuberculosis may readily have taken place in a range of Pleistocene megafauna.
Orosháza site no. 10 (Southeast Hungary) contains the partially excavated archaeological remains ... more Orosháza site no. 10 (Southeast Hungary) contains the partially excavated archaeological remains of an 11-13th century CE Muslim merchant village and its cemetery located in close proximity to Christian villages of the same era. The skeleton of a young woman (grave no. 16) from the last phase of the cemetery use was identified with rhinomaxillary lesions associated with lepromatous leprosy. The right parietal bone also exhibited signs of cranial trauma, possibly caused by symbolic trepanation, a well-known ritual practice in the 9-11th century CE Carpathian Basin. The retrospective diagnosis of the disease was supported by ancient DNA analysis, as the samples were positive for Mycobacterium leprae aDNA, shown to be of genotype 3. Contrary to the general practice of the era, the body of the young female with severe signs of leprosy was interred among the regular graves of the Muslim cemetery in Orosháza, which may reflect the unique cultural background of the community.
They lived in the 18th century in a small town of northern Hungary. The macroscopic examination o... more They lived in the 18th century in a small town of northern Hungary. The macroscopic examination of body No 54 showed a severely deformed neck and back region; body No 29 had no characteristic marks of any illnesses. The CT scan data of the bodies and their 3D reconstructions showed no skeletal evidence of tuberculosis, despite the positive results of their paleomicrobiological studies. The deformity of body No 54 turned to be a developmental abnormality of unknown origin, but no Pott's gibbus was present.
The perpetual burden of tuberculosis (TB) keeps drawing the focus of research on this disease. Am... more The perpetual burden of tuberculosis (TB) keeps drawing the focus of research on this disease. Among other risk factors (e.g., poor living conditions, malnutrition, smoking, HIV infection, etc.), being in close contact with a TB infected person requires special attention. For a better understanding of the disease, paleopathological investigations concerning TB have been carried out with various techniques for a long a time; nevertheless, analysis of incidence among family members is hardly possible in past populations. An exceptional group of naturally mummified individuals, the collection of the Vác mummies (Hungary, 18th century CE), is known about the large TB incidence rate, which has been revealed by aDNA analysis. Besides the high rate of TB infection, another interesting aspect of the collection is that in some cases, the family connections could be reconstructed. In this paper, we present the mycocerosic acid profiles gained by HPLC-HESI-MS measurements of two Vác mummies, w...
Highlights d Rapid lipoproteomics assay in Mycobacterium smegmatis d Identifies L-arabinose ABC t... more Highlights d Rapid lipoproteomics assay in Mycobacterium smegmatis d Identifies L-arabinose ABC transporter substrate-binding protein MSMEG_1712 d L-arabinofuranose uptake via cognate ABC transporter MSMEG_1709-1711 d Crystal structure of MSMEG_1712 bound to L-arabinofuranose
10e Rencontre du Groupe d’Anthropologie et d’Archéologie Funéraire, May 23, 2018
International audienceLa léproserie médiévale Saint-Thomas d’Aizier (fouillée de 1998 à 2010) est... more International audienceLa léproserie médiévale Saint-Thomas d’Aizier (fouillée de 1998 à 2010) est située en pleine forêt de Brotonne et compte parmi les propriétés de l’abbaye de Fécamp (Normandie, France). Seule la chapelle romane, dédiée à Thomas Becket, subsiste à l’état de ruines. Petit édifice rural a priori sans importance notable, il présente l’intérêt d’être intégralement conservé et offre l’opportunité très rare d’une fouille quasi exhaustive. Fondé vers la fin du XIIe siècle et abandonné au cours du XVIe siècle, l’établissement n’est plus fréquenté ensuite que de façon sporadique. Il est progressivement gagné par la forêt, ce qui a permis une fossilisation de l’enclos et la sauvegarde des vestiges. En principe, une léproserie est un centre de soins dévolus aux seuls lépreux/ses. À Aizier, l’étude des sources historiques et archéologiques a permis de comprendre l’organisation de cet établissement, son origine, son mode de fonctionnement et son évolution dans le temps avec des ruptures par rapport à sa destination d’origine (sexe, âge, pathologies). L’analyse de la population inhumée apporte non seulement un éclairage inédit sur les conditions de vie, la structuration des espaces et la nature des défunts, mais aussi sur les soins donnés aux malades accueillis dans cette communauté pénitentielle de lépreux. En effet, la population enterrée à Aizier est particulièrement intéressante pour l’étude de la lèpre au Moyen Âge, mais aussi pour connaître la perception de cette maladie et mieux appréhender ses implications sociales et thérapeutiques
The salivary peroxidase system has been described as inhibitory, and the main product, hypothiocy... more The salivary peroxidase system has been described as inhibitory, and the main product, hypothiocyanite (OSCN -), inhibits glycolysis and oxygen uptake (Carlsson et al., 1983). However, the similar lactoperoxidase (LPO) system is known to be protective under anaerobic conditions, at least in the short term (Carlsson, 1980). In the present study, the long-term effect of the LPO system on bacterial growth and acid production was investigated, by means of experimental microbial plaque samples. Dental plaque is an open ecosystem in which bacteria grow on a surface in a microbial film and are subjected to a fluctuating nutrient supply. The behavior of organisms under these conditions is likely to differ from that of bacteria in batch or continuous cultures (Wimpenny, 1981). An artificial mouth is a laboratory microcosm which enables plaque bacteria to be grown under conditions analogous to those found in vivo. Earlier work with this type of model demonstrated that 'Streptococcus mitior' LPA-1 produced sufficient hydrogen peroxide (H202) to antagonize Streptococcus rattus (mutans) BHT in a mixed plaque on teeth, and to activate the peroxidase system when LPO was present (Donoghue et al., 1985).
Tuberculosis is a significant global disease today, so understanding its origins and history is i... more Tuberculosis is a significant global disease today, so understanding its origins and history is important. It is primarily a lung infection and is transmitted by infectious aerosols from person to person, so a high population density encourages its spread. The causative organism is Mycobacterium tuberculosis, an obligate pathogen in the M. tuberculosis complex that also contains closely related species, such as Mycobacterium bovis, that primarily infect animals. Typical bone lesions occur in about 5% of untreated infections. These can be recognized in historical and archaeological material, along with nonspecific paleopathology such as new bone formation (periostitis), especially on ribs. Based on such lesions, tuberculosis has been found in ancient Egypt, pre-Columbian America, and Neolithic Europe. The detection of M. tuberculosis ancient DNA (aDNA) by using PCR led to the development of the new field of paleomicrobiology. As a result, a large number of tuberculosis cases were rec...
The bacillus Calmette–Guérin (BCG) vaccine has been in use for prevention of tuberculosis for ove... more The bacillus Calmette–Guérin (BCG) vaccine has been in use for prevention of tuberculosis for over a century. It remains the only widely available tuberculosis vaccine and its protective efficacy has varied across geographical regions. Since it was developed, the BCG vaccine strain has been shared across different laboratories around the world, where use of differing culture methods has resulted in genetically distinct strains over time. Whilst differing BCG vaccine efficacy around the world is well documented, and the reasons for this may be multifactorial, it has been hypothesized that genetic differences in BCG vaccine strains contribute to this variation. Isolates from an historic archive of lyophilized BCG strains were regrown, DNA was extracted and then whole-genome sequenced using Oxford Nanopore Technologies. The resulting whole-genome data were plotted on a phylogenetic tree and analysed to identify the presence or absence of regions of difference (RDs) and single-nucleotid...
HAL (Le Centre pour la Communication Scientifique Directe), Aug 28, 2018
International audienceLeprosy was widespread in Mediaeval Europe but molecular evidence indicates... more International audienceLeprosy was widespread in Mediaeval Europe but molecular evidence indicates geographical differences in the Mycobacterium leprae genotypes found at different times and locations. M. leprae requires a living host, and different human populations are associated with different lineages. Data are available from the UK and Scandinavia, Central, Southern and Eastern Europe, but little is known of the molecular characteristics of leprosy from Northern France. The paleopathology of leprosy is distinctive, so enables recognition of the disease in established cases. Therefore, nasal scrapings, and samples from ribs, femurs and toes, were taken from 15 individuals with typical paleopathology at the leprosarium of Saint Thomas d’Aizier (1350-1450 CE). After grinding to a powder, samples were demineralised in EDTA/Proteinase K at 56oC, mixed on a bead beater then split into 2 aliquots. One was treated with 0.1M PTB to break any covalent cross-links then both aliquots were incubated in lysis buffer containing guanidium thiocyanate. DNA was captured by silica or precipitated from the silica supernatants. Real-time PCR was used, with primers and probes for the M. leprae repetitive sequences RLEP (37 copies/cell) and RepLep (15 copies/cell). Eleven individuals were strongly positive for M. leprae DNA, two were weakly positive and two were negative. The stronger positive samples were genotyped. Unlike M. leprae ancient DNA from central and southern Europe, these Norman strains were of genotype 3I. However, in two individuals a variant M. leprae 3I-1 type was also found that has only once been reported previously, from 800-900 years earlier. This was in a skeleton from Great Chesterfield, East Anglia, UK, dated to 600 CE. This variant appears to be intermediate between sub-type 2F and 3I
Whole genome analysis of Mycobacterium tuberculosis isolates from recurrent episodes of tuberculo... more Whole genome analysis of Mycobacterium tuberculosis isolates from recurrent episodes of tuberculosis, Finland, 1995-2013
International audienceDans l’Europe médiévale, la lèpre était une affection largement répandue. C... more International audienceDans l’Europe médiévale, la lèpre était une affection largement répandue. Cependant, des preuves moléculaires indiquent l’existence de différents génotypes du Mycobacterium leprae selon les lieux de découverte et les époques. M. leprae nécessite l’hébergement par un être vivant et diverses lignées sont associées à différentes populations humaines. Des données sont disponibles pour le Royaume-Uni, la Scandinavie, l’Europe centrale, du Sud et de l’Est, mais peu sont accessibles pour caractériser moléculairement la lèpre dans le Nord de la France. La paléopathologie de la lèpre est caractéristique et permet la reconnaissance de la maladie sur des cas établis. Des échantillons osseux montrant des signes de lèpre ont été prélevés à partir de divers sites : Lisieux (IVe – VIIe s.), Vendeuil-Caply (Ve-VIe s.), Neuville-sur-Escaut (début à milieu VIe s.) et la léproserie de Saint Thomas d’Aizier (fin XIIe-début XVIe s.). Quand cela était possible, des échantillons ont ...
To give an insight into the different manifestations of leprosy and their biological consequences... more To give an insight into the different manifestations of leprosy and their biological consequences in the Avar Age of the Hungarian Duna-Tisza Interfluve, two cases from the 7th-century-CE osteoarchaeological series of Kiskundorozsma–Daruhalom-dűlő II (Hungary; n = 94) were investigated. Based on the macromorphology of the bony changes indicative of Hansen’s disease,KD271(a middle-aged male) andKD520(a middle-aged female) represent the two extremes of leprosy.KD271appears to have an advanced-stage, long-standing near-lepromatous or lepromatous form of the disease, affecting not only the rhinomaxillary region but also both upper and lower limbs. This has led to severe deformation and disfigurement of the involved anatomical areas of the skeleton, resulting in his inability to perform the basic activities of daily living, such as eating, drinking, grasping, standing or walking. The skeleton ofKD520shows no rhinomaxillary lesions and indicates the other extreme of leprosy, a near-tuberc...
The characterisation of ancient tuberculosis is not totally dependent on the recovery of intact g... more The characterisation of ancient tuberculosis is not totally dependent on the recovery of intact genomes. Judicious combinations of ancient DNA fragments and specific lipid biomarkers provide unambiguous diagnosis and these protocols are capable of refinement and extension. Currently, there is no direct evidence for exclusive co-evolution of humans and tuberculosis. A developing body of data suggests that the initial evolution of tuberculosis may readily have taken place in a range of Pleistocene megafauna.
Orosháza site no. 10 (Southeast Hungary) contains the partially excavated archaeological remains ... more Orosháza site no. 10 (Southeast Hungary) contains the partially excavated archaeological remains of an 11-13th century CE Muslim merchant village and its cemetery located in close proximity to Christian villages of the same era. The skeleton of a young woman (grave no. 16) from the last phase of the cemetery use was identified with rhinomaxillary lesions associated with lepromatous leprosy. The right parietal bone also exhibited signs of cranial trauma, possibly caused by symbolic trepanation, a well-known ritual practice in the 9-11th century CE Carpathian Basin. The retrospective diagnosis of the disease was supported by ancient DNA analysis, as the samples were positive for Mycobacterium leprae aDNA, shown to be of genotype 3. Contrary to the general practice of the era, the body of the young female with severe signs of leprosy was interred among the regular graves of the Muslim cemetery in Orosháza, which may reflect the unique cultural background of the community.
They lived in the 18th century in a small town of northern Hungary. The macroscopic examination o... more They lived in the 18th century in a small town of northern Hungary. The macroscopic examination of body No 54 showed a severely deformed neck and back region; body No 29 had no characteristic marks of any illnesses. The CT scan data of the bodies and their 3D reconstructions showed no skeletal evidence of tuberculosis, despite the positive results of their paleomicrobiological studies. The deformity of body No 54 turned to be a developmental abnormality of unknown origin, but no Pott's gibbus was present.
The perpetual burden of tuberculosis (TB) keeps drawing the focus of research on this disease. Am... more The perpetual burden of tuberculosis (TB) keeps drawing the focus of research on this disease. Among other risk factors (e.g., poor living conditions, malnutrition, smoking, HIV infection, etc.), being in close contact with a TB infected person requires special attention. For a better understanding of the disease, paleopathological investigations concerning TB have been carried out with various techniques for a long a time; nevertheless, analysis of incidence among family members is hardly possible in past populations. An exceptional group of naturally mummified individuals, the collection of the Vác mummies (Hungary, 18th century CE), is known about the large TB incidence rate, which has been revealed by aDNA analysis. Besides the high rate of TB infection, another interesting aspect of the collection is that in some cases, the family connections could be reconstructed. In this paper, we present the mycocerosic acid profiles gained by HPLC-HESI-MS measurements of two Vác mummies, w...
Highlights d Rapid lipoproteomics assay in Mycobacterium smegmatis d Identifies L-arabinose ABC t... more Highlights d Rapid lipoproteomics assay in Mycobacterium smegmatis d Identifies L-arabinose ABC transporter substrate-binding protein MSMEG_1712 d L-arabinofuranose uptake via cognate ABC transporter MSMEG_1709-1711 d Crystal structure of MSMEG_1712 bound to L-arabinofuranose
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Papers by Helen Donoghue