Mycobacterium leprae

From MicrobeWiki, the student-edited microbiology resource

A Microbial Biorealm page on the genus Mycobacterium leprae

Classification

Higher order taxa

Bacteria; Actinobacteria; Actinobacteria; Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae ; Mycobacterium [Others may be used. Use NCBI link to find]

Species

NCBI: Taxonomy

Mycobacterium leprae

Description and significance

Mycobacterium leprae is responsible for leprosy or Hansen's disease. Cases of leprosy have been recorded as early as 600 B.C. In 2004, The World Health Organization reported that there were 407,791 new cases of leprosy. Leprosy is a serious world issue, in Brazil, India, Democratic of Congo, Tanzania, Nepal, Mozambique, Madagascar, Angola and the Central African Republic leprosy is a major problem. Mycobacterium leprae is an intracellular bacterium, infecting nerve, skin and mucosal cells. In laboratory environments, Mycobacterium leprae is cultured on the feet of mice or on nine banded armadillos due to the inability to culture in vitro.

Describe the appearance, habitat, etc. of the organism, and why it is important enough to have its genome sequenced. Describe how and where it was isolated.

Genome structure

There are 3,268,203 nucleotides comprising the single circular chromosome of M. leprae. There are 2770 genes with in M. leprae. This is composed of coding for 1605 proteins and contains 1115 pseudogenes, primarily genes that were involved in metabolism but genes involved with DNA repair(mutT, dnaQ, alkA, dinX, and dinP genes) and detoxification(peroxidase genes). Many of the pseudogenes were involved in catabolism, the biosynthetic pathways tend to be well conserved. This was likely due to a number of recombination events, deletions and decay. Only 49% of the genome encodes for proteins. There is a 57% GC content. The genome was finished being sequenced in 10/02/2001 by the Sanger Institute.



Describe the size and content of the genome. How many chromosomes? Circular or linear? Other interesting features? What is known about its sequence? Does it have any plasmids? Are they important to the organism's lifestyle?

Cell structure and metabolism

Mycobacterium leprae is a acid fast Gram positive bacterium. With a slow doubling time of 27 hours. The slow doubling time is due to the restricted intake of nutrients through the pores in the large waxy walls. Mycobacterium have a unique lipid that makes up their membranes that give them their unique characteristic. The mycolic acids are very large lipid with chains ranging from 60 to 80 carbons long(7). Covalent bonds link these lipids to one another forming a very thick surrounding that is solid at room temperature. This large hydrophobic shell preventing polar molecules such as germicides used in hospitals. This slow doubling time is common with in Mycobacteria, it also makes it paricularly hard to fight.

Many of the pseudogenes primarily occur in the metabolic pathways. Entire metabolic pathways have been lost to this genomic down sizing. M. leprae can no longer produce siderophores, a key part of oxidative, microaerophilic and anarobic chains. Many regulatory elements of metabolism have also been lost and also many catabolic pathways too. M. leprae is dependent on the host cell to provide many of the nutrients and metabolites. This coupled metabolism shows how M. leprae has evoled as into a parasitic role. In the laboratory it was found that ideal metabolism(based on ATP synthesis and occurs at 33 degrees C and at a pH between 5.1 and 5.6(2).

Describe any interesting features and/or cell structures; how it gains energy; what important molecules it produces.


Ecology

Describe any interactions with other organisms (included eukaryotes), contributions to the environment, effect on environment, etc.

Pathology

How does this organism cause disease? Human, animal, plant hosts? Virulence factors, as well as patient symptoms.

M. leprae is responsible for the disease leprosy(1). In 2006, there were 219,826 cases of leprosy reported. It primarily affects the peripheral nerves and skin(9). It is also known to affect the central nervous system, mucus lining of the mouth, throat and lungs. Patients often experience numbness, skin lessions, joint pain and weakness. Lesions of the skin can leave individuals physically maimed and socially shunned. Unlike Mycobacterium tuberculosis, HIV doesn't change the rate of infection or the severity of the infection of M. leprae. Individuals infected with both HIV and leprosy, do not see an increased virulence of leprosy of HIV. This is due to leprosy's long incubational times and slow growth rate. The slow growth rate may allow for the hosts immune system to fight M. leprae even with a immunodefiency(9).

Mycobacterium leprae is able to infect Transmission of the disease is either from infected individual to non-infected individual or from infected individual to environment to non-infected individual(1). Current research suggests that M. leprae that lingers in the environment maybe the reason for relapses and epidemics in specific regions. Samples were taken from 15 different villages in the Ghatapur area that had recent outbreaks of leprosy. It was found that 33.3% of the samples contained DNA from M. leprae(12). Another study from the State of Espririto Santa, Brazil, collected 37 nine-banded armadillos and tested them for M. leprae. 11 individuals tested positive for the bacterium, which is almost 30% of the collected individuals. It wasns't untill 1975, that the first case of animal to human transmission of leprosy was reported(10). The number of cases has increase as the demand for armadillo products, such as stuffed armadillos and armadillo skin belts, have become popular novelties. Since 1975 there have been more than 5000 wild armadillos with confirmed cases of leprosy in the states of Arkansas, Louisiana, Mississippi, and Texas(13)

Application to Biotechnology

Does this organism produce any useful compounds or enzymes? What are they and how are they used?

Current Research

Enter summaries of the most recent research here--at least three required

References

1) Walker, S., Lockwood, D. "Leprosy". Clinics in Dermatology. 2007. Volume 25. p. 165-172.

2) [1] Wheeler, P.R. "Metabolism in Mycobacterium leprae: its relation to other research on M. leprae and to aspects of metablism in other mycobacteria and intracellular parasites." International Journal of Leprosy and other Mycobacterial Disease. June 1984. Volume 2. p. 208-230.

3) [2] Franzblau, S.G., Harris, E.B. "Biophysical optima for metabolism of Mycobacterium leprae". Journal of Clinical MicrobiologyEiglmeier K, Parkhill J, Honore N, Garnier T, Tekaia F, Telenti A, Klatser P, James KD, Thomson NR, Wheeler PR, Churcher C, Harris D, Mungall K, Barrell BG, Cole ST. . June 1988. Volume 6. p. 1124-1129.

4) [3] Wheeler, P.R. "Metabolism in Mycobacterium leprae, M. tuberculosis and other pathogenic mycobacteria". British Medical Bulletin. 1988. Volume 44. p. 547-561.

5) Eiglmeier K, Parkhill J, Honore N, Garnier T, Tekaia F, Telenti A, Klatser P, James KD, Thomson NR, Wheeler PR, Churcher C, Harris D, Mungall K, Barrell BG, Cole ST. "The decaying genome of Mycobacterium leprae". Leprosy Review. Dec 2001. Issue 72, Volume 4. 387-398.

6) Vissa VD, Brennan PJ."The genome of Mycobacterium leprae: a minimal mycobacterial gene set". Genome Biology. 2001. Issue 8, Volume 2. reviews 1023.1-1023.8.

7) [4] Cole ST, Eiglmeier K, Parkhill J, James KD, Thomson NR, Wheeler PR, Honore N, Garnier T, Churcher C, Harris D, Mungall K, Basham D, Brown D, Chillingworth T, Connor R, Davies RM, Devlin K, Duthoy S, Feltwell T, Fraser A, Hamlin N, Holroyd S, Hornsby T, Jagels K, Lacroix C, Maclean J, Moule S, Murphy L, Oliver K, Quail MA, Rajandream MA, Rutherford KM, Rutter S, Seeger K, Simon S, Simmonds M, Skelton J, Squares R, Squares S, Stevens K, Taylor K, Whitehead S, Woodward JR, Barrell BG. "Massive gene decay in the leprosy bacillus". Nature. Feb 22, 2001. 409. p. 1007-1011.

8) Marri PR, Bannatine JP, Golding GB. "Comparative genomics of metabolic pathways in Mycobacterium species: gene duplication, gene decay and lateral gene transfer". Feberation of European Microbiological Societies. 2006. Review 30. p.906-625.

9)D. M. Scollard, L. B. Adams, T. P. Gillis, J. L. Krahenbuhl, R. W. Truman, D. L. Williams. The Continuing Challenges of Leprosy. CLINICAL MICROBIOLOGY REVIEWS, Apr. 2006, p. 338–381

10)Duarte, P., Azevedo de Paula Antunes, J. M., Tomimori-Yamashita, J. Detection of Mycobacterium leprae infection in wild nine-banded armadillos (Dasypus novemcinctus)using the rapid ML Flow test. Revista da Sociedade Brasileira de Medicina Tropical 40(1):86-87, jan-fev, 2007

11) Murray, R. A., Siddiqui,M. R. Mendillo, M., Krahenbuhl, J., Kaplan, G. Mycobacterium leprae Inhibits Dendritic Cell Activation and Maturation. The Journal of Immunology. October 12,2006. p.338-344

12) Lavania M., Katoch K., Sachan P., Dubey A., Kapoor S., Kashyap M., Chauhan D.S., Singh H.B., Sharma V.D., Jadhav R.S., Katoch V.M. Detection of Mycobacterium leprae DNA from soil samples by PCR targeting RLEP sequences. Journal of Communicable Diseases. 2006 Mar;38(3):269-73

13) Truman, R. Leprosy in wild Armadillos. Leprosy Review. 2005 Sep;76(3):198-208

Edited by Kenton Collup, student of Rachel Larsen and Kit Pogliano