Leprosy, also known as Hansen’s disease, remains one of the most neglected bacterial infections globally, primarily caused by the species Mycobacterium leprae. Affecting an estimated 200,000 new individuals worldwide each year, the disease manifests as chronic skin lesions and nerve damage, often stigmatizing affected populations. While M. leprae has been extensively studied, much less is known about Mycobacterium lepromatosis, a related but distinct species that was identified relatively recently, first in clinical cases in the United States in 2008. Subsequent discoveries found M. lepromatosis circulating in red squirrels in the British Isles in 2016, hinting at a wider ecological and geographical presence than previously suspected. The new study spearheaded by the Laboratory of Microbial Paleogenomics at Institut Pasteur, in conjunction with over 40 researchers spanning multiple continents, meticulously analyzed DNA from nearly 800 samples encompassing both ancient human remains and modern clinical cases to reconstruct the evolutionary landscape of this elusive pathogen.

Utilizing state-of-the-art ancient DNA extraction and genome sequencing techniques, the researchers were able to recover genetic components of M. lepromatosis from archaeological specimens dated to approximately 1,000 years ago, hailing from regions in Canada and Argentina. Despite the vast geographical separation between these sites, genomic analyses revealed an astonishingly close relationship between the strains, indicating rapid and widespread dissemination of the bacterium throughout the Americas centuries before European arrival. Phylogenetic reconstructions demonstrated that although these strains represent two distinct branches within the Mycobacterium genus, they share a tighter genetic affinity with each other than with any other known pathogenic species, suggesting a unique and interconnected evolutionary trajectory specific to the American continent.

Further genomic characterization uncovered multiple previously unrecognized lineages of M. lepromatosis, including an ancestral branch that diverged over 9,000 years ago yet remains active in infecting humans today, particularly in North America. This finding not only pushes the timeline of the pathogen’s presence far deeper into prehistory but also unveils a long-standing diversification process that has thus far eluded scientific exploration. These revelations imply that the bacterial species responsible for leprosy in the Americas possesses a far more complex evolutionary and epidemiological history than previously conceived, possibly involving unknown animal reservoirs and environmental niches that have yet to be identified.

Intriguingly, the research also sheds light on the transcontinental movements of M. lepromatosis, notably connecting the strains found in British red squirrels to an American lineage introduced to the British Isles during the 19th century. This evidence underscores the ability of the pathogen to traverse vast distances alongside human or commercial activities, facilitating the introduction and establishment of leprosy bacilli across disparate regions. Such movements highlight the intricate relationship between human migration, commerce, and the spread of infectious diseases, emphasizing the importance of global surveillance and historical context in understanding present-day pathogen dynamics.

Dr. María Lopopolo, the study’s first author and a leading figure at the Laboratory of Microbial Paleogenomics, emphasized the transformative nature of these findings, stating that the recognized pre-European presence of M. lepromatosis redefines the epidemiological narrative surrounding leprosy in the Americas. The identification of the disease as endemic among Indigenous populations prior to European colonization challenges entrenched beliefs and calls for a reevaluation of historical medical interpretations. This evolving understanding fosters greater appreciation for the complex interplays between humans and pathogens over millennia and the ongoing legacy of ancient infections in contemporary communities.

A pivotal aspect of this research is its strong collaborative engagement with Indigenous communities whose ancestral remains were studied. Ethical considerations were paramount throughout the project; communities were integrally involved in decisions concerning the handling and analysis of archaeological specimens. The research team ensured that all ancient DNA and related materials were respectfully returned when requested, and employed adaptable data-sharing platforms that respected Indigenous data sovereignty and cultural sensitivities. This model of research exemplifies best practices for integrating scientific inquiry with social responsibility and community partnership, setting a precedent for future work in paleogenomics and infectious disease history.

Technically, the study combined high-throughput sequencing with advanced bioinformatics tools to meticulously assemble and compare ancient and modern genomes of M. lepromatosis. These approaches enabled the identification of genetic markers and evolutionary relationships that would have been undetectable through traditional microbiological methods. The integration of archaeological context, such as radiocarbon dating and anthropological data, enriched the interpretations and painted a comprehensive picture of the pathogen’s persistence and adaptation through diverse historical epochs and environments.

The revelations stemming from this research hold profound implications for contemporary public health and infectious disease management. Understanding the deep evolutionary roots and diversification of M. lepromatosis informs epidemiologists about the long-term dynamics of leprosy transmission, potential reservoirs, and reservoirs’ geographic distributions. It opens new avenues for investigating the potential existence of non-human hosts in the Americas and elsewhere, which could be critical in predicting and controlling future outbreaks. Moreover, the discovery accentuates the necessity of integrating ancient DNA studies into mainstream infectious disease research to uncover hidden dimensions of pathogen biology and history.

Lead author Nicolás Rascovan, helming the Laboratory of Microbial Paleogenomics at Institut Pasteur, highlighted the broader significance of the findings. By unraveling the ancient genomic signatures of M. lepromatosis, scientists can better appreciate the intricate evolutionary dance between humans and their microbial adversaries. Such insights pave the way for innovative strategies in tracking disease origins, understanding pathogen resilience, and ultimately, improving therapeutic interventions. The study exemplifies the power of combining ancient and modern genetic evidence to rewrite medical histories and deepen our grasp of pathogens that have shaped human societies across millennia.

The coming publication in Science marks a major milestone in microbial paleogenomics and infectious disease epidemiology. It demonstrates how meticulous cross-disciplinary investigations can dismantle historical narratives anchored in incomplete evidence and foster more nuanced, scientifically grounded understandings. This pioneering work not only addresses critical gaps in the history of leprosy but also serves as a beacon for future studies aiming to illuminate the ancient roots of other neglected tropical diseases, thereby enriching the tapestry of human-pathogen co-evolution.

In conclusion, the identification of Mycobacterium lepromatosis as an ancient, endemic leprosy pathogen in the Americas prior to European colonization revolutionizes our comprehension of the disease’s origins and dissemination. The study combines rigorous ancient DNA analysis, comprehensive evolutionary genetics, and ethical collaboration with Indigenous communities to highlight the complexity and persistence of a pathogen once overlooked. This research underscores the transformative potential of integrating paleogenomic methodologies into infectious disease studies and paves the way for nuanced future explorations of global disease histories.

Subject of Research: Human tissue samples
Article Title: Uncovering pre-European contact leprosy in the Americas and its enduring persistence
News Publication Date: 29-May-2025
Image Credits: © Nicolas Rascovan, Institut Pasteur
Keywords: Evolutionary genetics, Paleontology, Phylogenetics, Bacterial pathogens

Leprosy, also known as Hansen’s disease, is a chronic infectious condition affecting primarily the skin and peripheral nerves, and has been plaguing humanity for millennia. Traditionally, research and historical records have focused heavily on M. leprae, the species most commonly associated with the disease, especially in Europe and Asia. However, M. lepromatosis, only identified in 2008, has emerged as a crucial piece of the puzzle, particularly due to its predominance in cases reported in the Americas. Unlike M. leprae, whose introduction aligns closely with European colonization patterns, the evolutionary and historical trajectory of M. lepromatosis remained largely enigmatic until now.

The investigative team, led by Maria Lopopolo, undertook a comprehensive genomic analysis aimed at elucidating the presence, diversity, and historical timeline of M. lepromatosis in the Americas. Utilizing both contemporary DNA sequences and ancient genetic material extracted from archaeological human remains dating to periods before European arrival, the researchers mapped the distribution of M. lepromatosis across the continent. This dual approach allowed them to peer into the past, bridging modern molecular techniques with paleomicrobiology to chart the evolutionary history of this neglected pathogen.

Prior to this study, genomic data of M. lepromatosis were scarce and geographically limited. Available sequences mainly originated from a handful of Mexican patients and red squirrels from parts of Great Britain and Ireland, which constrained the ability to understand the bacterium’s variability and distribution. Such limitations hindered deeper insights into how and when the bacterium had spread into the Americas or interacted with human populations. By expanding the dataset with ancient DNA samples, the new research delivers critical evidence that challenges previous epidemiological models.

The analysis revealed that M. lepromatosis was endemic in human groups throughout the Americas well before European colonization. Specifically, ancient DNA screenings from pre-contact ancestral remains identified M. lepromatosis infections in diverse geographical regions spanning from northern to southern parts of the continent. This widespread presence suggests that M. lepromatosis had established itself over centuries, if not millennia, within Native American communities. Consequently, its epidemiological history is far more complex than a mere post-contact introduction.

Importantly, the study emphasizes that these findings do not dispute the well-documented introduction of M. leprae by Europeans and Africans during colonial times, which undoubtedly contributed to the modern epidemiology of leprosy in the Americas. Instead, the nuanced results indicate that the two species have distinctly different histories on the continent. While M. leprae’s dissemination aligns with documented migration and trade routes, M. lepromatosis appears to have had an independent, pre-contact trajectory, underscoring a much earlier chapter in the history of infectious diseases within indigenous populations.

This revelation carries profound implications for our understanding of human-pathogen coevolution. The presence of M. lepromatosis in pre-Columbian America invites a reconsideration of how infectious diseases developed and spread in isolation from Old World influences. It underscores the need to incorporate indigenous epidemiological histories that have been historically overlooked, both in scientific scholarship and in public health frameworks targeting leprosy.

The technical methodology employed was meticulous, incorporating high-throughput sequencing technologies adapted for degraded ancient samples. This enabled the recovery of pathogen genetic material from skeletal remains dated prior to the 15th century, a cutting-edge achievement that opens new vistas in paleopathology. Alongside this, comparative genomics analyses helped define the phylogenetic positioning of the recovered M. lepromatosis strains relative to contemporary isolates, revealing evolutionary divergences that predate European contact.

Moreover, the study sheds light on the zoonotic potential of M. lepromatosis, a dimension underscored by the presence of genetically similar strains in non-human hosts such as red squirrels in Europe. These cross-species associations provoke intriguing questions about the ecological niches and transmission dynamics of the bacterium, particularly whether animal reservoirs contributed to its persistence or geographical spread before human colonization events.

From a clinical perspective, distinguishing between M. leprae and M. lepromatosis carries significant weight. Both species cause different forms and severities of leprosy, with variations in disease progression and response to treatment. Historically, the lumping of these pathogens under a single disease umbrella may have obscured critical insights needed for tailored therapeutic strategies, especially in endemic regions of the Americas where M. lepromatosis predominates.

The study’s interdisciplinary approach also exemplifies the power of integrating genomics, archaeology, infectious disease biology, and anthropology to solve long-standing scientific mysteries. It bridges temporal gaps between ancient historical records and cutting-edge molecular biology, enriching our narratives about pathogen evolution and human history. This holistic perspective is essential for comprehensively tackling the legacies of infectious diseases.

In conclusion, this research fundamentally revises prevailing narratives on the origins and diversity of leprosy in the Americas. It reveals that Mycobacterium lepromatosis, a bacterium only recently identified, has been silently infecting indigenous populations across the continent for centuries prior to European colonization. These insights challenge simplified stories of post-contact disease introduction and open new pathways for understanding the complexity of human-pathogen interactions in the Americas. As the scientific community reassesses leprosy’s evolutionary history, these findings could stimulate renewed attention towards neglected tropical diseases and their deep historical roots.

The significance of uncovering pre-contact leprosy infections extends beyond academic curiosity—it holds profound implications for modern public health policies, diagnosis, and surveillance in endemic areas. By acknowledging the ancient and endemic nature of M. lepromatosis infections, health authorities can better anticipate patterns of disease persistence and transmission. Furthermore, the revelation may inspire new research exploring other pathogens that might share similarly underappreciated historical trajectories within indigenous populations.

This study exemplifies how advances in paleogenomics can revolutionize our understanding of diseases once thought well-characterized. It challenges us to reexamine the complex webs of interaction between humans and their microbial companions throughout history, emphasizing that even ancient DNA holds lessons with contemporary relevance. As research continues, the story of leprosy in the Americas promises to inform broader discussions on migration, colonization, and the invisible biological legacies carried forward across generations.

Subject of Research: Leprosy in the Americas, Mycobacterium lepromatosis, paleogenomics, infectious disease history

Article Title: Pre-European contact leprosy in the Americas and its current persistence

News Publication Date: 29-May-2025

Web References: http://dx.doi.org/10.1126/science.adu7144

Keywords: leprosy, Mycobacterium lepromatosis, Mycobacterium leprae, ancient DNA, paleogenomics, infectious diseases, pre-Columbian America, Hansen’s disease, pathogen evolution, indigenous populations