Mycobacterium leprae

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Mycobacterium leprae
Mycobacterium leprae.jpeg
Microphotograph of Mycobacterium leprae, the small brick-red rods in clusters, taken from a skin lesion. Source: CDC
Scientific classification
Kingdom: Bacteria
Phylum: Actinobacteria
Order: Actinomycetales
Suborder: Corynebacterineae
Family: Mycobacteriaceae
Genus: Mycobacterium
Species: M. leprae
Binomial name
Mycobacterium leprae
Hansen, 1874

Mycobacterium leprae, also known as Hansen’s coccus spirilly, mostly found in warm tropical countries, is a gram-positive bacterium that causes leprosy (Hansen's disease).[1] It is an intracellular, pleomorphic, acid-fast bacterium.[2] M. leprae is an aerobic bacillus (rod-shaped) surrounded by the characteristic waxy coating unique to mycobacteria. In size and shape, it closely resembles Mycobacterium tuberculosis. Due to its thick waxy coating, M. leprae stains with a carbol fuchsin rather than with the traditional Gram stain. The culture takes several weeks to mature.

Optical microscopy shows M. leprae in clumps, rounded masses, or in groups of bacilli side by side, and ranging from 1–8 μm in length and 0.2–0.5 μm in diameter.[3]

It was discovered in 1873 by the Norwegian physician Gerhard Armauer Hansen, who was searching for the bacteria in the skin nodules of patients with leprosy. It was the first bacterium to be identified as causing disease in humans.[4][5][verification needed] The organism has never been successfully grown on an artificial cell culture medium.[2] Instead, it has been grown in mouse foot pads and more recently in nine-banded armadillos because they, like humans, are susceptible to leprosy. This can be used as a diagnostic test for the presence of bacilli in body lesions of suspected leprosy patients. The difficulty in culturing the organism appears to be because it is an obligate intracellular parasite that lacks many necessary genes for independent survival. The complex and unique cell wall that makes members of the Mycobacterium genus difficult to destroy is apparently also the reason for the extremely slow replication rate.

Virulence factors include a waxy exterior coating, formed by the production of mycolic acids unique to Mycobacterium.

M. leprae was sensitive to dapsone (diaminodiphenylsulfone, the first effective treatment which was discovered for leprosy in the 1940s), but resistance against this antibiotic has developed over time. Therapy with dapsone alone is now strongly contraindicated. Currently, a multidrug treatment (MDT) is recommended by the World Health Organization, including dapsone, rifampicin and clofazimine. In patients receiving the MDT, a high proportion of the bacilli die within a short amount of time without immediate relief of symptoms. This suggests many symptoms of leprosy must be due in part to the presence of dead cells.

Pathogenesis[edit]

M. leprae replicates intracellularly histocytes and nerve cells and has two forms. One form is tuberculoid, which induces a cell-mediated response that limits its growth. Through this form M. leprae multiplies at the site of entry, usually the skin, invading and colonizing Schwann cells. The microbe then induces T-helper lymphocytes, epitheloid cells, and giant cell infiltration of the skin, causing infected individuals to exhibit large flattened patches with raised and elevated red edges on their skin. These patches have dry, pale, hairless centers, accompanied by a loss of sensation on the skin. The loss of sensation may develop as a result of invasion of the peripheral sensory nerves. The macule at the cutaneous site of entry and the loss of pain sensation are key clinical indications that an individual has a tuberculoid form of leprosy.

The second form of leprosy is the lepromatous form. This form of the microbe proliferates within the macrophages at the site of entry. It also grows within the epithelial tissues of the face and ear lobes. The suppressor T-cells that are induced are numerous, however the epitheloid and giant cells are rare or absent. With cell-mediated immunity impaired, large numbers of M. leprae appear in the macrophages and the infected patients develop papules at the entry site, marked by a folding of the skin. Gradual destruction of cutaneous nerves lead to what is referred to as "classic lion face." Extensive penetration of this microbe may lead to severe body damage; for example the loss of bones, fingers, and toes.

Mycobacterium leprae genome[edit]

M. leprae has the longest doubling time of all known bacteria and has thwarted every effort at culture in the laboratory.[6] Comparing the genome sequence of M. leprae with that of M. tuberculosis provides clear explanations for these properties, and reveals an extreme case of reductive evolution. Less than half of the genome contains functional genes. Gene deletion and decay appear to have eliminated many important metabolic activities, including siderophore production, part of the oxidative and most of the microaerophilic and anaerobic respiratory chains, and numerous catabolic systems and their regulatory circuits.[7]

The first genome sequence of a strain of M. leprae, was completed in 1998.[7] The genome sequence of a strain originally isolated in Tamil Nadu, India and designated TN, was completed in 2013. The sequence was obtained by a combined approach, employing automated DNA sequence analysis of selected cosmids and whole-genome 'shotgun' clones. After the finishing process, the genome sequence was found to contain 3,268,203 base pairs (bp), and to have an average G+C content of 57.8%, values much lower than the corresponding values for M. tuberculosis, which are 4, 441,529 bp and 65.6% G+C.[8]

About 1500 genes are common to both M. leprae and M. tuberculosis. The comparative analysis suggests both mycobacteria derived from a common ancestor and, at one stage, had gene pools of similar size. Downsizing from a genome of 4.42 Mbp, such as that of M. tuberculosis, to one of 3.27 Mbp would account for the loss of some 1200 protein-coding sequences. There is evidence that many of the genes that were present in the genome of the common ancestor of M. leprae and M. tuberculosis have been lost by recombination in the M. leprae genome.[9]

Information from the completed genome can be useful to develop diagnostic skin tests, to understand the mechanisms of nerve damage and drug resistance and to identify novel drug targets for rational design of new therapeutic regimens and drugs to treat leprosy and its complications.

Ancient Mycobacterium leprae[edit]

Almost complete sequences of M. leprae from medieval skeletons with osteological lesions suggestive of leprosy from different Europe geographic origins were obtained using DNA capture techniques and high-throughput sequencing (HTS). Ancient sequences were compared with those of modern strains from biopsies of leprosy patients representing diverse genotypes and geographic origins, giving new insights in the understanding of evolution, course through history, phylogeography of the leprosy bacillus and the disappearance of leprosy from Europe.

Verena J. Schuenemann et al. demonstrated a remarkable genomic conservation during the past 1000 years and a close similarity between modern and ancient strains, suggesting that the sudden decline of leprosy in Europe was not due to a losing of virulence but due to extraneous factors, such as other infectious diseases, changes in host immunity or improved social conditions.[10]

Diagnostic criteria for leprosy[edit]

Diagnostic criteria for leprosy: The diagnosis of leprosy is primarily a clinical one. In one Ethiopian study, the following criteria had a sensitivity of 94% with a positive predictive value of 98% in diagnosing leprosy. Diagnosis was based on one or more of three signs:
1) Hypopigmented or reddish skin patches with definite loss of sensation
2) Thickened peripheral nerves
3) Acid-fast bacilli on skin smears or biopsy material
4) BCG vaccine
5) Ricaballicin and Monopoliatic drug combinations

References[edit]

  1. ^ Ryan KJ, Ray CG, ed. (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. pp. 451–3. ISBN 0-8385-8529-9. 
  2. ^ a b McMurray DN (1996). "Mycobacteria and Nocardia.". In Baron S. et al.. Baron's Medical Microbiology (4th ed.). University of Texas Medical Branch. ISBN 0-9631172-1-1. 
  3. ^ Shinnick, Thomas M. (2006). "Mycobacterium leprae". In Dworkin, Martin; Falkow, Eugene; Rosenberg; Schleifer, Karl-Heinz; Stackebrandt, Erko. The Prokaryotes. Springer. pp. 934–944. doi:10.1007/0-387-30743-5_35. ISBN 978-0-387-25493-7. 
  4. ^ Hansen GHA (1874). "Undersøgelser Angående Spedalskhedens Årsager (Investigations concerning the etiology of leprosy)". Norsk Mag. Laegervidenskaben (in Norwegian) 4: 1–88. 
  5. ^ Irgens L (2002). "The discovery of the leprosy bacillus". Tidsskr nor Laegeforen 122 (7): 708–9. PMID 11998735. 
  6. ^ Truman RW, Krahenbuhl JL (2001). "Viable M. leprae as a research reagent". Int. J. Lepr. Other Mycobact. Dis. 69 (1): 1–12. PMID 11480310. 
  7. ^ a b Cole ST, Brosch R, Parkhill J, et al. (1998). "Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence". Nature 393 (6685): 537–44. doi:10.1038/31159. PMID 9634230. 
  8. ^ Narayanan S, Deshpande U (2013). "Whole-Genome Sequences of Four Clinical Isolates of Mycobacterium tuberculosis from Tamil Nadu, South India". Genome Announc 1 (3). doi:10.1128/genomeA.00186-13. PMC 3707582. PMID 23788533. 
  9. ^ Cole ST, Eiglmeier K, Parkhill J, et al. (2001). "Massive gene decay in the leprosy bacillus". Nature 409 (6823): 1007–11. doi:10.1038/35059006. PMID 11234002. 
  10. ^ Schuenemann VJ, Singh P, Mendum TA, et al. (July 2013). "Genome-wide comparison of medieval and modern Mycobacterium leprae". Science 341 (6142): 179–83. doi:10.1126/science.1238286. PMID 23765279. 

External links[edit]