Long-term Survival and Virulence of Mycobacterium Leprae in Amoebal Cysts

Overview

Journal PLoS Negl Trop Dis

Specialties Infectious Diseases
Tropical Medicine

Date 2014 Dec 19

PMID 25521850

Citations 43

Authors

William H Wheat

Amy L Casali

Vincent Thomas

John S Spencer

Ramanuj Lahiri

Diana L Williams

Gerald E McDonnell

Mercedes Gonzalez-Juarrero

Patrick J Brennan

Mary Jackson

Affiliations

Soon will be listed here.

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.

Citing Articles

Leprosy.

Grijsen M, Nguyen T, Pinheiro R, Singh P, Lambert S, Walker S Nat Rev Dis Primers. 2024; 10(1):90.

PMID: 39609422 DOI: 10.1038/s41572-024-00575-1.

Potentially Pathogenic Free-Living Amoebae Isolated from Soil Samples from Warsaw Parks and Squares.

Hendiger-Rizo E, Chmielewska-Jeznach M, Poreda K, Rizo Liendo A, Koryszewska-Baginska A, Oledzka G Pathogens. 2024; 13(10).

PMID: 39452766 PMC: 11510524. DOI: 10.3390/pathogens13100895.

Human Skin as an Ex Vivo Model for Maintaining and Leprosy Studies.

de Paula N, Leite M, Bertoluci D, Soares C, Rosa P, Cipriani Frade M Trop Med Infect Dis. 2024; 9(6).

PMID: 38922047 PMC: 11209558. DOI: 10.3390/tropicalmed9060135.

Ticks are unlikely to play a role in leprosy transmission in the Comoros (East Africa) as they do not harbour DNA.

Krausser L, Chauvaux E, Van Dyck-Lippens M, Yssouf A, Assoumani Y, Tortosa P Front Med (Lausanne). 2023; 10:1238914.

PMID: 37859857 PMC: 10582737. DOI: 10.3389/fmed.2023.1238914.

's Infective Capacity Is Associated with Activation of Genes Involved in PGL-I Biosynthesis in a Schwann Cells Infection Model.

Chavarro-Portillo B, Soto C, Guerrero M Int J Mol Sci. 2023; 24(10).

PMID: 37240073 PMC: 10218259. DOI: 10.3390/ijms24108727.

References

Lahiri R, Randhawa B, Krahenbuhl J . Effects of purification and fluorescent staining on viability of Mycobacterium leprae. Int J Lepr Other Mycobact Dis. 2006; 73(3):194-202. View

Kyle D, Noblet G . Seasonal distribution of thermotolerant free-living amoebae. II. Lake Issaqueena. J Protozool. 1987; 34(1):10-5. DOI: 10.1111/j.1550-7408.1987.tb03122.x. View

De Jonckheere J, Michel R . Species identification and virulence of Acanthamoeba strains from human nasal mucosa. Parasitol Res. 1988; 74(4):314-6. DOI: 10.1007/BF00539451. View

Thomas V, Herrera-Rimann K, Blanc D, Greub G . Biodiversity of amoebae and amoeba-resisting bacteria in a hospital water network. Appl Environ Microbiol. 2006; 72(4):2428-38. PMC: 1449017. DOI: 10.1128/AEM.72.4.2428-2438.2006. View

Schuster F . Cultivation of pathogenic and opportunistic free-living amebas. Clin Microbiol Rev. 2002; 15(3):342-54. PMC: 118083. DOI: 10.1128/CMR.15.3.342-354.2002. View

Bass P, Bischoff P . Seasonal variability in abundance and diversity of soil gymnamoebae along a short transect in southeastern USA. J Eukaryot Microbiol. 2001; 48(4):475-9. DOI: 10.1111/j.1550-7408.2001.tb00182.x. View

Anderson O . Abundance of terrestrial gymnamoebae at a northeastern U. S. site: a four-year study, including the El Niño winter of 1997-1998. J Eukaryot Microbiol. 2000; 47(2):148-55. DOI: 10.1111/j.1550-7408.2000.tb00024.x. View

Coulon C, Collignon A, McDonnell G, Thomas V . Resistance of Acanthamoeba cysts to disinfection treatments used in health care settings. J Clin Microbiol. 2010; 48(8):2689-97. PMC: 2916629. DOI: 10.1128/JCM.00309-10. View

Truman R, Andrews P, Robbins N, Adams L, Krahenbuhl J, Gillis T . Enumeration of Mycobacterium leprae using real-time PCR. PLoS Negl Trop Dis. 2008; 2(11):e328. PMC: 2570796. DOI: 10.1371/journal.pntd.0000328. View

10.

Scollard D, Adams L, Gillis T, Krahenbuhl J, Truman R, Williams D . The continuing challenges of leprosy. Clin Microbiol Rev. 2006; 19(2):338-81. PMC: 1471987. DOI: 10.1128/CMR.19.2.338-381.2006. View

11.

Kerr-Pontes L, Barreto M, Evangelista C, Rodrigues L, Heukelbach J, Feldmeier H . Socioeconomic, environmental, and behavioural risk factors for leprosy in North-east Brazil: results of a case-control study. Int J Epidemiol. 2006; 35(4):994-1000. DOI: 10.1093/ije/dyl072. View

12.

Barreto J, Bisanzio D, Guimaraes L, Spencer J, Vazquez-Prokopec G, Kitron U . Spatial analysis spotlighting early childhood leprosy transmission in a hyperendemic municipality of the Brazilian Amazon region. PLoS Negl Trop Dis. 2014; 8(2):e2665. PMC: 3916250. DOI: 10.1371/journal.pntd.0002665. View

13.

Nacapunchai D, Kino H, Ruangsitticha C, Sriwichai P, Ishih A, Terada M . A brief survey of free-living amebae in Thailand and Hamamatsu District, Japan. Southeast Asian J Trop Med Public Health. 2002; 32 Suppl 2:179-82. View

14.

Taylor C, ELLISTON E, GIDEON H . Asymptomatic infections in leprosy. Int J Lepr. 1965; 33(3):Suppl:716-31. View

15.

Davis G, Ray N, Lahiri R, Gillis T, Krahenbuhl J, Williams D . Molecular assays for determining Mycobacterium leprae viability in tissues of experimentally infected mice. PLoS Negl Trop Dis. 2013; 7(8):e2404. PMC: 3750008. DOI: 10.1371/journal.pntd.0002404. View

16.

Stanley S, Cox J . Host-pathogen interactions during Mycobacterium tuberculosis infections. Curr Top Microbiol Immunol. 2013; 374:211-41. DOI: 10.1007/82_2013_332. View

17.

Mura M, Bull T, Evans H, Sidi-Boumedine K, McMinn L, Rhodes G . Replication and long-term persistence of bovine and human strains of Mycobacterium avium subsp. paratuberculosis within Acanthamoeba polyphaga. Appl Environ Microbiol. 2006; 72(1):854-9. PMC: 1352277. DOI: 10.1128/AEM.72.1.854-859.2006. View

18.

Truman R, Fine P . 'Environmental' sources of Mycobacterium leprae: issues and evidence. Lepr Rev. 2010; 81(2):89-95. View

19.

Martinez A, Lahiri R, Pittman T, Scollard D, Truman R, Moraes M . Molecular determination of Mycobacterium leprae viability by use of real-time PCR. J Clin Microbiol. 2009; 47(7):2124-30. PMC: 2708532. DOI: 10.1128/JCM.00512-09. View

20.

Donoghue H, Holton J, Spigelman M . PCR primers that can detect low levels of Mycobacterium leprae DNA. J Med Microbiol. 2001; 50(2):177-182. DOI: 10.1099/0022-1317-50-2-177. View