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TICKS AS POTENTIAL VECTORS OF MYCOBACTERIUM LEPRAE: USE OF TICK CELL LINES TO CULTURE THE BACILLI AND GENERATE TRANSGENIC STRAINS
Produção científica do Laboratório de Microbiologia Celular.
Author summary: Leprosy is a slow-progressing and extremely debilitating disease; the armadillo is the only animal model able to mimic the symptoms observed in humans. In addition, the causative agent, Mycobacterium leprae, is not cultivable in vitro. Due to these constraints the chain of transmission is still not yet completely understood. We know, however, that at least two animals, armadillos in the Americas and red squirrels in the UK, are natural reservoirs of the bacillus, although their role in disease epidemiology is unclear. This information raised the following question: Can ticks carry leprosy from wild animals to humans? In the present study we demonstrated that artificially-infected female cayenne ticks are able to transmit the bacillus to their offspring, which were then able to transmit it to rabbits during bloodfeeding. We were able to grow M. leprae in vitro in a tick cell line for the first time. We also generated the first transgenic M. leprae strain, making the pathogen fluorescent in order to monitor its viability in real time. We believe that this new methodology will boost the screening of new drugs useful for control of leprosy, as well as improving understanding of how M. leprae causes disease.
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Abstract
Leprosy is an infectious disease caused by Mycobacterium leprae and frequently resulting in irreversible deformities and disabilities. Ticks play an important role in infectious disease transmission due to their low host specificity, worldwide distribution, and the biological ability to support transovarial transmission of a wide spectrum of pathogens, including viruses, bacteria and protozoa. To investigate a possible role for ticks as vectors of leprosy, we assessed transovarial transmission of M. leprae in artificially-fed adult female Amblyomma sculptum ticks, and infection and growth of M. leprae in tick cell lines. Our results revealed M. leprae RNA and antigens persisting in the midgut and present in the ovaries of adult female A. sculptum at least 2 days after oral infection, and present in their progeny (eggs and larvae), which demonstrates the occurrence of transovarial transmission of this pathogen. Infected tick larvae were able to inoculate viable bacilli during blood-feeding on a rabbit. Moreover, following inoculation with M. leprae, the Ixodes scapularis embryo-derived tick cell line IDE8 supported a detectable increase in the number of bacilli for at least 20 days, presenting a doubling time of approximately 12 days. As far as we know, this is the first in vitro cellular system able to promote growth of M. leprae. Finally, we successfully transformed a clinical M. leprae isolate by inserting the reporter plasmid pCHERRY3; transformed bacteria infected and grew in IDE8 cells over a 2-month period. Taken together, our data not only support the hypothesis that ticks may have the potential to act as a reservoir and/or vector of leprosy, but also suggest the feasibility of technological development of tick cell lines as a tool for large-scale production of M. leprae bacteria, as well as describing for the first time a method for their transformation.
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Public Library of Science
Citation
FERREIRA, Jéssica da Silva et al. Ticks as potential vectors of mycobacterium leprae: use of tick cell lines to culture the bacilli and generate transgenic strains. PLoS Neglected Tropical Diseases, v. 12, n. 12, p. 1-25, 19 Dec. 2018.DOI
10.1371/journal.pntd.0007001ISSN
1935-2727Notes
Produção científica do Laboratório de Biologia Molecular Aplicada a Micobactérias.Produção científica do Laboratório de Microbiologia Celular.
Author summary: Leprosy is a slow-progressing and extremely debilitating disease; the armadillo is the only animal model able to mimic the symptoms observed in humans. In addition, the causative agent, Mycobacterium leprae, is not cultivable in vitro. Due to these constraints the chain of transmission is still not yet completely understood. We know, however, that at least two animals, armadillos in the Americas and red squirrels in the UK, are natural reservoirs of the bacillus, although their role in disease epidemiology is unclear. This information raised the following question: Can ticks carry leprosy from wild animals to humans? In the present study we demonstrated that artificially-infected female cayenne ticks are able to transmit the bacillus to their offspring, which were then able to transmit it to rabbits during bloodfeeding. We were able to grow M. leprae in vitro in a tick cell line for the first time. We also generated the first transgenic M. leprae strain, making the pathogen fluorescent in order to monitor its viability in real time. We believe that this new methodology will boost the screening of new drugs useful for control of leprosy, as well as improving understanding of how M. leprae causes disease.
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