Redefining the treponemal history through pre-Columbian genomes from Brazil.

The origins of treponemal diseases have long remained unknown, especially considering the sudden onset of the first syphilis epidemic in the late 15th century in Europe and its hypothesized arrival from the Americas with Columbus' expeditions1,2. Recently, ancient DNA evidence has revealed various treponemal infections circulating in early modern Europe and colonial-era Mexico3-6. However, there has been to our knowledge no genomic evidence of treponematosis recovered from either the Americas or the Old World that can be reliably dated to the time before the first trans-Atlantic contacts. Here, we present treponemal genomes from nearly 2,000-year-old human remains from Brazil. We reconstruct four ancient genomes of a prehistoric treponemal pathogen, most closely related to the bejel-causing agent Treponema pallidum endemicum. Contradicting the modern day geographical niche of bejel in the arid regions of the world, the results call into question the previous palaeopathological characterization of treponeme subspecies and showcase their adaptive potential. A high-coverage genome is used to improve molecular clock date estimations, placing the divergence of modern T. pallidum subspecies firmly in pre-Columbian times. Overall, our study demonstrates the opportunities within archaeogenetics to uncover key events in pathogen evolution and emergence, paving the way to new hypotheses on the origin and spread of treponematoses.

Advancing the understanding of treponemal disease in the past and present.

Syphilis was perceived to be a new disease in Europe in the late 15th century, igniting a debate about its origin that continues today in anthropological, historical, and medical circles. We move beyond this age-old debate using an interdisciplinary approach that tackles broader questions to advance the understanding of treponemal infection (syphilis, yaws, bejel, and pinta). How did the causative organism(s) and humans co-evolve? How did the related diseases caused by Treponema pallidum emerge in different parts of the world and affect people across both time and space? How are T. pallidum subspecies related to the treponeme causing pinta? The current state of scholarship in specific areas is reviewed with recommendations made to stimulate future work. Understanding treponemal biology, genetic relationships, epidemiology, and clinical manifestations is crucial for vaccine development today and for investigating the distribution of infection in both modern and past populations. Paleopathologists must improve diagnostic criteria and use a standard approach for recording skeletal lesions on archaeological human remains. Adequate contextualization of cultural and environmental conditions is necessary, including site dating and justification for any corrections made for marine or freshwater reservoir effects. Biogeochemical analyses may assess aquatic contributions to diet, physiological changes arising from treponemal disease and its treatments (e.g., mercury), or residential mobility of those affected. Shifting the focus from point of origin to investigating who is affected (e.g., by age/sex or socioeconomic status) and disease distribution (e.g., coastal/ inland, rural/urban) will advance our understanding of the treponemal disease and its impact on people through time.

Rib lesions in a prehistoric Puebloan sample from southwestern Colorado.

An unusually high frequency of periosteal lesions of visceral rib surfaces was observed in a small, prehistoric skeletal series from southwestern Colorado. Lesions of this type have been concordant with pulmonary tuberculosis in three studies of human skeletal collections with known cause of death, and in a recent clinical investigation of rib dimensions in living patients with lung disorders. Diseases such as pneumonia and actinomycosis have also been found to cause these lesions, but in much lower frequencies. Archaeological evidence suggests that Puebloan farmers of Sleeping Ute Mountain's southern piedmont, from which the sample is drawn, endured unusually harsh environmental conditions punctuated by severe drought and exacerbated by escalating warfare. It is argued here that these environmental stressors increased susceptibility to an opportunistic respiratory infection reminiscent of tuberculosis, and possibly also some form of pneumonia, resulting in high rates of active disease previously noted only in historic Puebloan peoples.

Treponema lecithinolyticum sp. nov., a small saccharolytic spirochaete with phospholipase A and C activities associated with periodontal diseases.

Strong phospholipase A (PLA) and phospholipase C (PLC) activities as potential virulence factors are the outstanding characteristics of eight strains of small oral spirochaetes isolated from deep periodontal lesions. By qualitative dot-blot DNA-DNA hybridization and 16S rDNA sequence comparison, these spirochaetes form a distinct phylogenetic group, with Treponema maltophilum as its closest cultivable relative. Growth of these treponemes, cells of which contain two endoflagella, one at each pole, was autoinhibited by the PLA-mediated production of lysolecithin unless medium OMIZ-Pat was prepared without lecithin. N-Acetylglucosamine was essential and D-ribose was stimulatory for growth. All isolates were growth-inhibited when 1% foetal calf serum was added to the medium. Growth on agar plates supplemented with human erythrocytes produced haemolysis. In addition to PLA and PLC, the new isolates displayed strong activities of alkaline and acid phosphatases, beta-galactosidase, beta-glucuronidase, N-acetyl-beta-glucosaminidase and sialidase, intermediate activities of C4- and C8-esterases, naphthol phosphohydrolase and alpha-fucosidase and a distinctive 30 kDa antigen detectable on Western blots. This phenotypically and genotypically homogeneous group is proposed as a novel species, Treponema lecithinolyticum sp. nov., with isolate OMZ 684T designated as the type strain. A molecular epidemiological analysis using a T. lecithinolyticum-specific probe showed this organism to be associated with affected sites when compared with unaffected sites of periodontitis patients. This association was more pronounced in patients with rapidly progressive periodontitis than in those with adult periodontitis.

Prehistoric juvenile rheumatoid arthritis in a precontact Louisiana native population reconsidered.

Descriptions of skeletal pathological conditions evident in the prehistoric Tchefuncte adolescent 16ST1-14883b are clarified. The basis is reaffirmed for assigning to the described pathological conditions a diagnostic perspective of juvenile rheumatoid arthritis or juvenile Lyme disease--a disease that mimics juvenile rheumatoid arthritis in its arthritic presentation--rather than of assigning them as representative of juvenile onset ankylosing spondylitis or other juvenile spondyloarthropathies. A hypothesis (Lewis [1994] Am. J. Phys. Anthropol. 93:455-475) is restated that 1) the spirochete Borrelia burgdorferi was the infectious agent responsible for prevalence of adult rheumatoid arthritis in prehistoric southeastern Native American populations, 2) that B. burgdorferi is a possible cause of the arthritis evident in individual 16ST1-14883b, and 3) that antibodies to B. burgdorferi provided partial immunity to the related spirochete Treponema pallidum for the 16ST1 precontact Tchefuncte population from Louisiana, protecting them from severe treponemal response. Given the probable widespread existence of Ixodid tick vectors for B. burgdorferi in prehistoric North America, coupled with the existence of treponematosis, it follows that the transition of Native American hunting-gathering economies to more sedentary economies would predictably be linked to an increased incidence of treponematosis due to the loss of benefits of the above-stated partial immunity. In other words, as prehistoric Native American exposure to tick vectors for B. burgdorferi decreased, susceptibility to treponematosis increased. Inferences regarding biological controls interacting with and influencing prehistoric Native American migration patterns are suggested from the link of B. burgdorferi to an Ixodid tick common to northeast Asia.