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Long-term survival and virulence of Mycobacterium leprae in amoebal cysts
- Source :
- PLoS Neglected Tropical Diseases, Vol 8, Iss 12, p e3405 (2014), PLoS Neglected Tropical Diseases
- Publication Year :
- 2014
- Publisher :
- Public Library of Science (PLoS), 2014.
-
Abstract
- Leprosy is a curable neglected disease of humans caused by Mycobacterium leprae that affects the skin and peripheral nerves and manifests clinically in various forms ranging from self-resolving, tuberculoid leprosy to lepromatous leprosy having significant pathology with ensuing disfiguration disability and social stigma. Despite the global success of multi-drug therapy (MDT), incidences of clinical leprosy have been observed in individuals with no apparent exposure to other cases, suggestive of possible non-human sources of the bacteria. In this study we show that common free-living amoebae (FLA) can phagocytose M. leprae, and allow the bacillus to remain viable for up to 8 months within amoebic cysts. Viable bacilli were extracted from separate encysted cocultures comprising three common Acanthamoeba spp.: A. lenticulata, A. castellanii, and A. polyphaga and two strains of Hartmannella vermiformis. Trophozoites of these common FLA take up M. leprae by phagocytosis. M. leprae from infected trophozoites induced to encyst for long-term storage of the bacilli emerged viable by assessment of membrane integrity. The majority (80%) of mice that were injected with bacilli extracted from 35 day cocultures of encysted/excysted A. castellanii and A. polyphaga showed lesion development that was similar to mice challenged with fresh M. leprae from passage mice albeit at a slower initial rate. Mice challenged with coculture-extracted bacilli showed evidence of acid-fast bacteria and positive PCR signal for M. leprae. These data support the conclusion that M. leprae can remain viable long-term in environmentally ubiquitous FLA and retain virulence as assessed in the nu/nu mouse model. Additionally, this work supports the idea that M. leprae might be sustained in the environment between hosts in FLA and such residence in FLA may provide a macrophage-like niche contributing to the higher-than-expected rate of leprosy transmission despite a significant decrease in human reservoirs due to MDT.<br />Author Summary Leprosy is a progressive disease of the skin and nervous system caused by the bacillus, Mycobacterium leprae. Implementation of multiple drug therapy (MDT) for leprosy has significantly reduced the global cases of leprosy. Currently, only a few endemic countries remain where relatively high number of cases persists. Despite global reduction of leprosy and the concomitant decrease in human reservoirs, leprosy transmission and incidence have not declined as expected, suggesting a possible extra-human or environmental source of the bacilli. In the current study, we demonstrate that M. leprae can survive long-term within cysts of common environmental free-living amoebae. M. leprae residing in amoebal cysts for over 30 days remain fully capable of transferring disease to mouse footpads and retain viability phenotypes after several months residence within amoebal cysts. It is hypothesized that these protozoa provide an intracellular refuge for M. leprae in environments for which they would otherwise seem ill suited. Traits allowing bacilli to survive in macrophages may likely be acquired via an evolutionary response against predation by amoebae. The results from this work suggest alternative non-human reservoirs for M. leprae exist fostering further study to determine the role of amoebae in the transmission of this Mycobacterium to humans.
- Subjects :
- Bacterial Diseases
Bacilli
lcsh:Arctic medicine. Tropical medicine
lcsh:RC955-962
Mice, Nude
Virulence
Acanthamoeba
Tuberculoid leprosy
Microbiology
Mice
Phagocytosis
Leprosy
Medicine and Health Sciences
medicine
Animals
Humans
Amoebas
Amoeba
10. No inequality
Mycobacterium leprae
Protozoans
Lepromatous leprosy
Bacteria
biology
Macrophages
lcsh:Public aspects of medicine
Organisms
Public Health, Environmental and Occupational Health
Biology and Life Sciences
lcsh:RA1-1270
Tropical Diseases
biology.organism_classification
medicine.disease
Mycobacterium Leprae
Parasitic Protozoans
Coculture Techniques
3. Good health
Actinobacteria
Infectious Diseases
Research Article
Neglected Tropical Diseases
Subjects
Details
- Language :
- English
- ISSN :
- 19352735 and 19352727
- Volume :
- 8
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- PLoS Neglected Tropical Diseases
- Accession number :
- edsair.doi.dedup.....6daa0eb3866d0b64dc4c818a8423c1e8