Michel Signoli

Bio: Michel Signoli is an academic researcher from Aix-Marseille University. The author has contributed to research in topics: Plague (disease) & Yersinia pestis. The author has an hindex of 21, co-authored 99 publications receiving 1850 citations. Previous affiliations of Michel Signoli include Centre national de la recherche scientifique & University of Nice Sophia Antipolis.

Distinct clones of Yersinia pestis caused the black death.

Abstract: From AD 1347 to AD 1353, the Black Death killed tens of millions of people in Europe, leaving misery and devastation in its wake, with successive epidemics ravaging the continent until the 18(th) century. The etiology of this disease has remained highly controversial, ranging from claims based on genetics and the historical descriptions of symptoms that it was caused by Yersinia pestis to conclusions that it must have been caused by other pathogens. It has also been disputed whether plague had the same etiology in northern and southern Europe. Here we identified DNA and protein signatures specific for Y. pestis in human skeletons from mass graves in northern, central and southern Europe that were associated archaeologically with the Black Death and subsequent resurgences. We confirm that Y. pestis caused the Black Death and later epidemics on the entire European continent over the course of four centuries. Furthermore, on the basis of 17 single nucleotide polymorphisms plus the absence of a deletion in glpD gene, our aDNA results identified two previously unknown but related clades of Y. pestis associated with distinct medieval mass graves. These findings suggest that plague was imported to Europe on two or more occasions, each following a distinct route. These two clades are ancestral to modern isolates of Y. pestis biovars Orientalis and Medievalis. Our results clarify the etiology of the Black Death and provide a paradigm for a detailed historical reconstruction of the infection routes followed by this disease.

Detection of 400-year-old Yersinia pestis DNA in human dental pulp: An approach to the diagnosis of ancient septicemia

Abstract: Ancient septicemic plague epidemics were reported to have killed millions of people for 2 millenniums. However, confident diagnosis of ancient septicemia solely on the basis of historical clinical observations is not possible. The lack of suitable infected material has prevented direct demonstration of ancient septicemia; thus, the history of most infections such as plague remains hypothetical. The durability of dental pulp, together with its natural sterility, makes it a suitable material on which to base such research. We hypothesized that it would be a lasting refuge for Yersinia pestis, the plague agent. DNA extracts were made from the dental pulp of 12 unerupted teeth extracted from skeletons excavated from 16th and 18th century French graves of persons thought to have died of plague (“plague teeth”) and from 7 ancient negative control teeth. PCRs incorporating ancient DNA extracts and primers specific for the human β-globin gene demonstrated the absence of inhibitors in these preparations. The incorporation of primers specific for Y. pestis rpoB (the RNA polymerase β-subunit-encoding gene) and the recognized virulence-associated pla (the plasminogen activator-encoding gene) repeatedly yielded products that had a nucleotide sequence indistinguishable from that of modern day isolates of the bacterium. The specific pla sequence was obtained from 6 of 12 plague skeleton teeth but 0 of 7 negative controls (P < 0.034, Fisher exact test). A nucleic acid-based confirmation of ancient plague was achieved for historically identified victims, and we have confirmed the presence of the disease at the end of 16th century in France. Dental pulp is an attractive target in the quest to determine the etiology of septicemic illnesses detected in ancient corpses. Molecular techniques could be applied to this material to resolve historical outbreaks.

Evidence for Louse-Transmitted Diseases in Soldiers of Napoleon’s Grand Army in Vilnius

Abstract: Background. Many soldiers in Napoleon's Grand Army died of infectious diseases during its retreat from Russia. Because soldiers were commonly infested with body lice, it has been speculated that louse-borne infectious diseases, such as epidemic typhus (caused by Rickettsia prowazekii), were common. Methods. We investigated this possibility during recent excavations of a mass grave of Napoleon's soldiers in Vilnius, Lithuania. Segments of 5 body lice, identified morphologically and by polymerase chain reaction (PCR) amplification and sequencing, were found in earth from the grave that also contained fragments of soldiers' uniforms. Results. DNA of Bartonella quintana (the agent of trench fever) was identified by PCR and sequencing in 3 of the lice. Similarly, PCR and sequencing of dental pulp from the remains of 35 soldiers revealed DNA of B. quintana in 7 soldiers and DNA of R. prowazekii in 3 other soldiers. Conclusions. Our results show that louse-borne infectious diseases affected nearly one-third of Napoleon's soldiers buried in Vilnius and indicate that these diseases might have been a major factor in the French retreat from Russia.

Age and sex bias in the reconstruction of past population structures.

Abstract: Palaeodemographical studies are founded on the assumption that the sex and age distribution of the skeletal sample reflects the constitution of the original population. It is becoming increasingly clear, however, that the type and amount of information that may be derived from osteoarchaeological collections are related to the state of preservation of remains. This work proposes a new method to evaluate bone preservation, to identify age and sex biases in the preservation of human skeletal remains, and to assess whether differences in preservation patterns are more dependent on factors intrinsic or extrinsic to anatomical features of human bones. Three osteological collections and over 600 skeletons were observed. The state of preservation of human bones was assessed using three preservation indexes: the anatomical preservation index (API), the bone representation index (BRI), and the qualitative bone index (QBI). The results suggest that subadult skeletons are generally more poorly preserved and with bones less well-represented than adult skeletons. Among subadults, female and male skeletons have different patterns of preservation according to their age. This pattern of preservation depends on intrinsic anatomical properties of bones themselves, while external factors can only increase these differences in the state of preservation and representation of osseous remains. It is concluded from this that failure to recognize these differences may lead to misleading interpretations of paleodemography of past human populations.

Yersinia pestis Orientalis in remains of ancient plague patients.

Abstract: Yersinia pestis DNA was recently detected in human remains from 2 ancient plague pandemics in France and Germany. We have now sequenced Y. pestis glpD gene in such remains, showing a 93-bp deletion specific for biotype Orientalis. These data show that only Orientalis type caused the 3 plague pandemics.

Genetic Analyses from Ancient DNA

Abstract: ▪ Abstract About 20 years ago, DNA sequences were separately described from the quagga (a type of zebra) and an ancient Egyptian individual. What made these DNA sequences exceptional was that they were derived from 140- and 2400-year-old specimens. However, ancient DNA research, defined broadly as the retrieval of DNA sequences from museum specimens, archaeological finds, fossil remains, and other unusual sources of DNA, only really became feasible with the advent of techniques for the enzymatic amplification of specific DNA sequences. Today, reports of analyses of specimens hundreds, thousands, and even millions of years old are almost commonplace. But can all these results be believed? In this paper, we critically assess the state of ancient DNA research. In particular, we discuss the precautions and criteria necessary to ascertain to the greatest extent possible that results represent authentic ancient DNA sequences. We also highlight some significant results and areas of promising future research.

A draft genome of Yersinia pestis from victims of the Black Death

Abstract: Technological advances in DNA recovery and sequencing have drastically expanded the scope of genetic analyses of ancient specimens to the extent that full genomic investigations are now feasible and are quickly becoming standard. This trend has important implications for infectious disease research because genomic data from ancient microbes may help to elucidate mechanisms of pathogen evolution and adaptation for emerging and re-emerging infections. Here we report a reconstructed ancient genome of Yersinia pestis at 30-fold average coverage from Black Death victims securely dated to episodes of pestilence-associated mortality in London, England, 1348-1350. Genetic architecture and phylogenetic analysis indicate that the ancient organism is ancestral to most extant strains and sits very close to the ancestral node of all Y. pestis commonly associated with human infection. Temporal estimates suggest that the Black Death of 1347-1351 was the main historical event responsible for the introduction and widespread dissemination of the ancestor to all currently circulating Y. pestis strains pathogenic to humans, and further indicates that contemporary Y. pestis epidemics have their origins in the medieval era. Comparisons against modern genomes reveal no unique derived positions in the medieval organism, indicating that the perceived increased virulence of the disease during the Black Death may not have been due to bacterial phenotype. These findings support the notion that factors other than microbial genetics, such as environment, vector dynamics and host susceptibility, should be at the forefront of epidemiological discussions regarding emerging Y. pestis infections.

Genome sequences of the human body louse and its primary endosymbiont provide insights into the permanent parasitic lifestyle

Abstract: As an obligatory parasite of humans, the body louse (Pediculus humanus humanus) is an important vector for human diseases, including epidemic typhus, relapsing fever, and trench fever. Here, we present genome sequences of the body louse and its primary bacterial endosymbiont Candidatus Riesia pediculicola. The body louse has the smallest known insect genome, spanning 108 Mb. Despite its status as an obligate parasite, it retains a remarkably complete basal insect repertoire of 10,773 protein-coding genes and 57 microRNAs. Representing hemimetabolous insects, the genome of the body louse thus provides a reference for studies of holometabolous insects. Compared with other insect genomes, the body louse genome contains significantly fewer genes associated with environmental sensing and response, including odorant and gustatory receptors and detoxifying enzymes. The unique architecture of the 18 minicircular mitochondrial chromosomes of the body louse may be linked to the loss of the gene encoding the mitochondrial single-stranded DNA binding protein. The genome of the obligatory louse endosymbiont Candidatus Riesia pediculicola encodes less than 600 genes on a short, linear chromosome and a circular plasmid. The plasmid harbors a unique arrangement of genes required for the synthesis of pantothenate, an essential vitamin deficient in the louse diet. The human body louse, its primary endosymbiont, and the bacterial pathogens that it vectors all possess genomes reduced in size compared with their free-living close relatives. Thus, the body louse genome project offers unique information and tools to use in advancing understanding of coevolution among vectors, symbionts, and pathogens.

Yersinia pestis genome sequencing identifies patterns of global phylogenetic diversity

Abstract: Plague is a pandemic human invasive disease caused by the bacterial agent Yersinia pestis. We here report a comparison of 17 whole genomes of Y. pestis isolates from global sources. We also screened a global collection of 286 Y. pestis isolates for 933 SNPs using Sequenom MassArray SNP typing. We conducted phylogenetic analyses on this sequence variation dataset, assigned isolates to populations based on maximum parsimony and, from these results, made inferences regarding historical transmission routes. Our phylogenetic analysis suggests that Y. pestis evolved in or near China and spread through multiple radiations to Europe, South America, Africa and Southeast Asia, leading to country-specific lineages that can be traced by lineage-specific SNPs. All 626 current isolates from the United States reflect one radiation, and 82 isolates from Madagascar represent a second radiation. Subsequent local microevolution of Y. pestis is marked by sequential, geographically specific SNPs.