Editing Mycobacterium leprae

{{Short description|Bacterium that causes leprosy}}
{{Use mdy dates|date=July 2020}}
{{Speciesbox
| image = Mycobacterium_leprae.jpeg
| image_caption = Microphotograph of {{nowrap|''Mycobacterium leprae''}} taken from a skin lesion.<br />The small brick-red rod-shaped cells appear in clusters.<br />Source: CDC
| genus = Mycobacterium
| species = leprae
| authority = [[Gerhard Armauer Hansen|Hansen]], 1874
}}

'''''Mycobacterium leprae''''' (also known as the '''leprosy bacillus''' or '''Hansen's bacillus''') is one{{efn|The other is ''[[Mycobacterium lepromatosis]]''.}}
of the two species of  [[bacteria]] that cause [[Hansen's disease]] (leprosy),<ref name="pmid35678776">{{cite journal |vauthors=Serrano-Coll H, Cardona-Castro N |title=Neuropathic ulcers in leprosy: clinical features, diagnosis and treatment |journal=Journal of Wound Care |volume=31 |issue=Sup6 |pages=S32–S40 |date=June 2022 |pmid=35678776 |doi=10.12968/jowc.2022.31.Sup6.S32 |s2cid=249521365 |url=}}</ref> a chronic but curable infectious disease that damages the [[peripheral nerves]] and targets the skin, eyes, nose, and muscles.<ref>{{Cite web|url=https://microbiologysociety.org/publication/past-issues/mycobacteria/article/mycobacterium-leprae-the-cause-of-leprosy.html|title=Mycobacterium Leprae, the Cause of Leprosy|date=27 August 2014|website=Microbiology Society|access-date=November 12, 2019|archive-date=November 12, 2019|archive-url=https://web.archive.org/web/20191112005236/https://microbiologysociety.org/publication/past-issues/mycobacteria/article/mycobacterium-leprae-the-cause-of-leprosy.html|url-status=live}}</ref>

It is an [[Acid-fastness|acid-fast]], [[Gram-positive bacteria|Gram-positive]], rod shaped bacterium and an obligate [[intracellular parasite]], which means, unlike its relative ''[[Mycobacterium tuberculosis]]'', it cannot be grown in cell-free laboratory media.<ref name="Baron" /> This is likely due to gene deletion and decay that the genome of the species has experienced via [[reductive evolution]], which has caused the bacterium to depend heavily on its host for nutrients and [[metabolic intermediate]]s.<ref name="pmid21162636">{{cite journal | vauthors = Singh P, Cole ST | title = ''Mycobacterium leprae'': genes, pseudogenes and genetic diversity | journal = Future Microbiology | volume = 6 | issue = 1 | pages = 57–71 | date = January 2011 | pmid = 21162636 | pmc = 3076554 | doi = 10.2217/fmb.10.153 }}</ref>  It has a narrow host range and apart from humans, the only other natural hosts are [[nine-banded armadillo]] and [[red squirrels]].<ref name="pmid29665434">{{cite journal | vauthors = Sharma R, Singh P, Pena M, Subramanian R, Chouljenko V, Kim J, Kim N, Caskey J, Baudena MA, Adams LB, Truman RW | display-authors = 6 | title = Differential growth of Mycobacterium leprae strains (SNP genotypes) in armadillos | journal = Infection, Genetics and Evolution | volume = 62 | issue =  | pages = 20–26 | date = August 2018 | pmid = 29665434 | doi = 10.1016/j.meegid.2018.04.017 | s2cid = 4953934 }}</ref> 
The bacteria infect mainly [[macrophage]]s and [[Schwann cell]]s, and are typically found congregated as a [[Palisade (pathology)|palisade]].<ref name=":6" /><ref name="pmid33936067">{{cite journal |vauthors=Leal-Calvo T, Martins BL, Bertoluci DF, Rosa PS, de Camargo RM, Germano GV, Brito de Souza VN, Pereira Latini AC, Moraes MO |title=Large-Scale Gene Expression Signatures Reveal a Microbicidal Pattern of Activation in Mycobacterium leprae-Infected Monocyte-Derived Macrophages With Low Multiplicity of Infection |journal=Frontiers in Immunology |volume=12 |issue= |pages=647832 |date=2021 |pmid=33936067 |pmc=8085500 |doi=10.3389/fimmu.2021.647832 |url=|doi-access=free }}</ref>

''Mycobacterium leprae'' was sensitive to [[dapsone]] as a treatment alone, but since the 1960s, it has developed [[antibiotic resistance|resistance]] against this [[antibiotic]]. Currently, a multidrug treatment (MDT) is recommended by the [[World Health Organization]], including dapsone, [[rifampicin]], and [[clofazimine]]. The species was discovered in 1873 by the Norwegian physician [[Gerhard Armauer Hansen]], and was the first bacterium to be identified as a cause of disease in humans.<ref name="Hansen_1874"/>

== Microbiology ==
[[File:Leprosy Wade Fite stain 100x.jpg|thumb|Modified AFB staining in a case of lepromatous leprosy showing numerous rod shaped acid fast bacilli]]

''Mycobacterium leprae'' is an intracellular, [[pleomorphism (microbiology)|pleomorphic]], [[Endospore|non-sporing]], [[Motility|non-motile]], [[acid-fast]], [[pathogenic bacterium]].<ref name="Baron">{{cite book | vauthors = McMurray DN | chapter = Mycobacteria and Nocardia. | title = Baron's Medical Microbiology | editor = Baron S. | edition = 4th | publisher = University of Texas Medical Branch | year = 1996 | pmid = 21413269 | chapter-url = https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mmed.section.1833 | isbn = 978-0-9631172-1-2 | display-editors = etal | access-date = September 5, 2017 | archive-date = February 12, 2009 | archive-url = https://web.archive.org/web/20090212202626/http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mmed.section.1833 | url-status = live }}</ref> It is an [[Aerobic organism|aerobic]] [[bacillus]] (rod-shaped bacterium) with parallel sides and round ends, surrounded by the characteristic waxy coating of [[mycolic acid]] unique to [[mycobacteria]]. It is [[Gram-positive bacteria|Gram-positive]] by [[Gram stain]]ing, but ''Mycobacterium leprae'' was traditionally stained with  [[carbol fuchsin]] in the [[Ziehl–Neelsen stain]]. Because the bacilli are less acid-fast than ''[[Mycobacterium tuberculosis]]'' (MTB), the Fite-Faraco staining method, which has a lower acid concentration, is used now.<ref name="pmid35061916">{{cite journal |vauthors=Kalagarla S, Alluri R, Saka S, Godha V, Undavalli N, Kolalapudi SA |title=Efficacy of fluorescent microscopy versus modified Fite-Faraco stain in skin biopsy specimens of leprosy cases - a comparative study |journal=International Journal of Dermatology |volume=61 |issue=5 |pages=595–599 |date=May 2022 |pmid=35061916 |doi=10.1111/ijd.16046|s2cid=246165881 }}</ref><ref name="pmid35379512">{{cite journal |vauthors=Froes LA, Sotto MN, Trindade MA |title=Leprosy: clinical and immunopathological characteristics |journal=Anais Brasileiros de Dermatologia |volume=97 |issue=3 |pages=338–347 |date=2022 |pmid=35379512 |pmc=9133310 |doi=10.1016/j.abd.2021.08.006}}</ref>  In size and shape, it closely resembles MTB. The bacteria are found in the granulomatous lesions and are especially numerous in the nodules. This bacteria often occur in large numbers within the lesions of lepromatous leprosy and are usually grouped together as a [[Palisade (pathology)|palisade]].<ref name=":6">{{Cite web|url=https://www.who.int/lep/microbiology/en/|archive-url=https://web.archive.org/web/20130608081632/http://www.who.int/lep/microbiology/en/|url-status=dead|archive-date=June 8, 2013|title=Microbiology of M.leprae|website=World Health Organization}}</ref> 
By [[Optical microscope|optical microscopy]] of host cells, ''Mycobacterium leprae'' can be found singly or in clumps referred to as "globi", the bacilli can be straight or slightly curved, with a length ranging from 1–8 [[micrometre|μm]] and a diameter of 0.3 μm.<ref>{{cite book | vauthors = Shinnick TM | veditors = Dworkin M, Falkow S, Rosenberg E, Schleifer KH, Stackebrandt E |chapter=''Mycobacterium leprae'' |title=The Prokaryotes |publisher=Springer |year=2006 |isbn=978-0-387-25493-7 |pages=934–44 |doi=10.1007/0-387-30743-5_35 |url=https://zenodo.org/record/1232954 |access-date=July 14, 2019 |archive-date=September 29, 2020 |archive-url= https://web.archive.org/web/20200929112420/https://zenodo.org/record/1232954 |url-status=live }}</ref> The bacteria grow best at 27 to 30&nbsp;°C, making the skin, nasal mucosa and peripheral nerves primary targets for infection by ''Mycobacterium leprae''.<ref>{{cite book | vauthors = Gorbach SL, Bartlett JG, Blacklow NR | title=Infectious diseases | publisher=Saunders | publication-place=Philadelphia |page=1882 |date=1992 | isbn=0-7216-4168-7 | oclc=22346573}}</ref>

== Host range ==
''Mycobacterium leprae'' has a narrow host range and apart from humans the only other hosts are [[nine-banded armadillo]]s and [[red squirrels]],<ref name="pmid29665434"/>  and armadillos have been implicated as a source of [[zoonosis|zoonotic]] leprosy in humans.<ref name="pmid3051854">{{cite journal | vauthors = Walsh GP, Meyers WM, Binford CH, Gormus BJ, Baskin GB, Wolf RH, Gerone PJ | title = Leprosy as a zoonosis: an update | journal = Acta Leprologica | volume = 6 | issue = 1 | pages = 51–60 | date = 1988 | pmid = 3051854 | doi =  }}</ref> In the laboratory, mice can be infected and this is a useful [[animal model]].<ref name="pmid33660297">{{cite journal | vauthors = Adams LB | title = Susceptibility and resistance in leprosy: Studies in the mouse model | journal = Immunological Reviews | volume = 301 | issue = 1 | pages = 157–174 | date = May 2021 | pmid = 33660297 | pmc = 8252540 | doi = 10.1111/imr.12960 }}</ref>

=== Cultivation ===
''Mycobacterium leprae'' has an unusually lengthy [[doubling time]] (ranging from 12 to 14 days compared with 20 minutes for ''[[Escherichia coli]]''), as well as its inability to be cultured in the laboratory.<ref>{{cite web |title=Mycobacterium leprae |url=https://www.sciencedirect.com/topics/medicine-and-dentistry/mycobacterium-leprae |access-date=October 31, 2021 |archive-date=October 31, 2021 |archive-url=https://web.archive.org/web/20211031105224/https://www.sciencedirect.com/topics/medicine-and-dentistry/mycobacterium-leprae |url-status=live }}</ref><ref name="Truman_2001">{{cite journal | vauthors = Truman RW, Krahenbuhl JL | title = Viable M. leprae as a research reagent | journal = International Journal of Leprosy and Other Mycobacterial Diseases | volume = 69 | issue = 1 | pages = 1–12 | date = March 2001 | pmid = 11480310 }}</ref><ref>{{cite journal | vauthors = Gillis TP |title=Mycobacterium leprae |journal=Molecular Medical Microbiology (Second Edition) |year=2015 |pages=1655–1668 |doi=10.1016/B978-0-12-397169-2.00093-7|isbn=9780123971692 }}</ref> Because the organism is an [[obligate intracellular parasite]], it lacks many necessary genes for independent survival, causing difficulty in culturing the organism. The complex and unique cell wall that makes members of the genus ''[[Mycobacterium]]'' difficult to destroy is also the reason for its extremely slow replication rate. ''Mycobacterium leprae'' prefers cool temperatures, slightly acidic microaerophilic conditions, and prefers the use of lipids as an energy source over sugars. The growth conditions needed for ''Mycobacterium leprae'' are known, but an exact axenic medium to support the growth of ''Mycobacterium leprae'' still has yet to be discovered.<ref name=":3">Lahiri R, Adams LB. (2016) "Cultivation and viability determination of ''Mycobacterium leprae''", Chapter 5.3. ''In'' Scollard DM, Gillis TP (ed), International textbook of leprosy, [https://internationaltextbookofleprosy.org].</ref> Since ''in vitro'' cultivation is not generally possible, it has instead been grown in mouse foot pads,<ref name="pmid33660297"/> and in armadillos due to their low core body temperature.<ref>{{cite journal | vauthors = Sharma R, Singh P, Loughry WJ, Lockhart JM, Inman WB, Duthie MS, Pena MT, Marcos LA, Scollard DM, Cole ST, Truman RW | display-authors = 6 | title = Zoonotic Leprosy in the Southeastern United States | journal = Emerging Infectious Diseases | volume = 21 | issue = 12 | pages = 2127–2134 | date = December 2015 | pmid = 26583204 | pmc = 4672434 | doi = 10.3201/eid2112.150501 }}</ref><ref name=":3" />

== Metabolism ==
The [[reductive evolution]] experienced by the ''Mycobacterium leprae'' genome has impaired its metabolic abilities in comparison to other ''Mycobacterium'', specifically in its catabolic pathways.<ref name=":9">{{cite journal | vauthors = Borah K, Girardi KD, Mendum TA, Lery LM, Beste DJ, Lara FA, Pessolani MC, McFadden J | display-authors = 6 | title = Intracellular Mycobacterium leprae Utilizes Host Glucose as a Carbon Source in Schwann Cells | journal = mBio | volume = 10 | issue = 6 | date = December 2019 | pmid = 31848273 | pmc = 6918074 | doi = 10.1128/mBio.02351-19 | editor-first = Jon P. | editor-last = Boyle }}</ref>

=== Catabolism ===
''Mycobacterium leprae''{{'}}s inability to be grown in axenic media indicates its reliance on nutrients and intermediates from its host.<ref name=":7">{{cite journal | vauthors = Borah K, Kearney JL, Banerjee R, Vats P, Wu H, Dahale S, Manjari Kasibhatla S, Joshi R, Bonde B, Ojo O, Lahiri R, Williams DL, McFadden J | display-authors = 6 | title = GSMN-ML- a genome scale metabolic network reconstruction of the obligate human pathogen Mycobacterium leprae | journal = PLOS Neglected Tropical Diseases | volume = 14 | issue = 7 | pages = e0007871 | date = July 2020 | pmid = 32628669 | pmc = 7365477 | doi = 10.1371/journal.pntd.0007871 | veditors = Borlee BR | doi-access = free }}</ref> Many of the catabolic pathways present in other ''Mycobacterium'' species are compromised, due to the absence of enzymes that play key roles in degradation of nutrients.<ref name=":7" /> ''Mycobacterium leprae'' has lost the ability to use common carbon sources, such as acetate and galactose, in its central energy metabolism pathways.<ref name="pmid21162636" /> Additionally, lipid degradation is impaired, with deficits in key lipase enzymes, and other proteins involved in lipolysis.<ref name=":8">{{cite journal | vauthors = Cole ST, Eiglmeier K, Parkhill J, James KD, Thomson NR, Wheeler PR, Honoré 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 | display-authors = 6 | title = Massive gene decay in the leprosy bacillus | journal = Nature | volume = 409 | issue = 6823 | pages = 1007–1011 | date = February 2001 | pmid = 11234002 | doi = 10.1038/35059006 | bibcode = 2001Natur.409.1007C | s2cid = 4307207 }}</ref> Functional carbon catabolic pathways continue to exist in the species, such as the glycolytic pathway, the pentose phosphate pathway, and the TCA cycle.<ref name=":7" /> These deficiencies extensively restricts the microbe's growth to a limited number of carbon sources, such as host-derived intermediates.<ref name="pmid21162636" />

=== Anabolism ===
''Mycobacterium leprae'''s anabolic pathways have been largely unaffected by its reductive evolution.<ref name=":9" /> The species retains its ability for the synthesis of genetic material, such as purines, pyrimidines, nucleotides, and nucleosides, as well as the synthesis of all amino acids, except for methionine and lysine.<ref name=":7" />

== Genome ==
The first genome sequence of a strain of ''Mycobacterium leprae'' was completed in 2001, revealing 1604 protein-coding genes and another 1,116 pseudogenes.<ref name="Cole_2001" /> The genome sequence of a strain originally isolated in [[Tamil Nadu]], [[India]], and designated ''TN'', was completed in 2013. This genome sequence contains 3,268,203 [[base pair]]s (bp) and an average [[GC-content|G+C content]] of 57.8%, which is significantly less than ''M. tuberculosis'', which has 4,441,529 bp and 65.6% G+C.<ref>{{cite journal | vauthors = Narayanan S, Deshpande U | title = Whole-Genome Sequences of Four Clinical Isolates of Mycobacterium tuberculosis from Tamil Nadu, South India | journal = Genome Announcements | volume = 1 | issue = 3 | pages = e00186–13 | date = June 2013 | pmid = 23788533 | pmc = 3707582 | doi = 10.1128/genomeA.00186-13 }}</ref>

Comparing the [[genome]] sequence of ''Mycobacterium leprae'' with that of MTB reveals an extreme case of reductive [[evolution]]. Less than half of the genome contains functional [[genes]].  It is estimated approximately 2000 genes from ''Mycobacterium leprae'' genome has been lost.<ref name="Cole_2001" /> 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 respiration|anaerobic]] [[Respiration (physiology)|respiratory]] chains, and numerous [[catabolic]] systems and their regulatory circuits.<ref name="Cole_1998">{{cite journal | vauthors = Cole ST, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, Gordon SV, Eiglmeier K, Gas S, Barry CE, Tekaia F, Badcock K, Basham D, Brown D, Chillingworth T, Connor R, Davies R, Devlin K, Feltwell T, Gentles S, Hamlin N, Holroyd S, Hornsby T, Jagels K, Krogh A, McLean J, Moule S, Murphy L, Oliver K, Osborne J, Quail MA, Rajandream MA, Rogers J, Rutter S, Seeger K, Skelton J, Squares R, Squares S, Sulston JE, Taylor K, Whitehead S, Barrell BG | display-authors = 6 | title = Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence | journal = Nature | volume = 393 | issue = 6685 | pages = 537–544 | date = June 1998 | pmid = 9634230 | doi = 10.1038/31159 | doi-access = free | bibcode = 1998Natur.393..537C }}</ref> This reductive evolution is largely linked to the organism's development into an obligate intracellular bacterium.<ref name=":2">{{cite journal | vauthors = Chavarro-Portillo B, Soto CY, Guerrero MI | title = Mycobacterium leprae's evolution and environmental adaptation | journal = Acta Tropica | volume = 197 | pages = 105041 | date = September 2019 | pmid = 31152726 | doi = 10.1016/j.actatropica.2019.105041 | s2cid = 173188912 }}</ref>

=== Pseudogenes ===
Many of the genes that were present in the genome of the common ancestor of ''Mycobacterium leprae'' and ''M. tuberculosis'' have been lost in the ''Mycobacterium leprae'' genome.<ref name="Cole_2001">{{cite journal | vauthors = Cole ST, Eiglmeier K, Parkhill J, James KD, Thomson NR, Wheeler PR, Honoré 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 | display-authors = 6 | title = Massive gene decay in the leprosy bacillus | journal = Nature | volume = 409 | issue = 6823 | pages = 1007–1011 | date = February 2001 | pmid = 11234002 | doi = 10.1038/35059006 | s2cid = 4307207 | bibcode = 2001Natur.409.1007C }}</ref><ref name="pmid31152726" /> Due to ''Mycobacterium leprae's'' reliance on a host organism, many of the species' [[DNA repair]] functions have been lost, increasing the occurrence of [[Deletion (genetics)|deletion mutations]].<ref name=":2" /> Because the products supplied by these deleted genes are typically present in the host cells infected by ''Mycobacterium leprae'', the impact that the mutations have on the microbe is minimal, allowing for survival within the host despite its reduced genome.<ref>{{cite journal | vauthors = Vissa VD, Brennan PJ | title = The genome of Mycobacterium leprae: a minimal mycobacterial gene set | journal = Genome Biology | volume = 2 | issue = 8 | pages = REVIEWS1023 | date = 2001-08-03 | pmid = 11532219 | pmc = 138955 | doi = 10.1186/gb-2001-2-8-reviews1023 | doi-access = free }}</ref> Consequently, ''Mycobacterium leprae'' has undergone a dramatic reduction in genome size with the loss of many genes.<ref name="pmid21162636"/>  Over half of the pathogen's genome is now made up by pseudogenes due to the pathogen undergoing what is known as [[reductive evolution]].<ref name="pmid21162636" /> Among published genomes, ''Mycobacterium leprae'' contains the highest number of pseudogens (>1000).<ref name=":4" /> Many of these pseudogenes arose from insertions of stop codons which may have been caused by [[sigma factor]] dysfunction (a protein needed for initiation of transcription in bacteria) or the insertion of transposon- derived repetitive sequences.<ref>Akama T, Suzuki K, Tanigawa K, et al. Whole-genome tiling array analysis of ''Mycobacterium leprae'' RNA reveals high expression of pseudogenes and noncoding regions. J Bacteriol. 2009;191(10):3321–3327. DOI:10.1128/JB.00120-09</ref> Some of the ''Mycobacterium leprae'' pseudogens expression levels will alter upon infection of macrophages, which suggests that some ''Mycobacterium leprae'' pseudogens are not all "decayed" genes, but could also function in infection, intracellular replication, and replication.<ref name=":4">{{cite journal | vauthors = Nakamura K, Akama T, Bang PD, Sekimura S, Tanigawa K, Wu H, Kawashima A, Hayashi M, Suzuki K, Ishii N | display-authors = 6 | title = Detection of RNA expression from pseudogenes and non-coding genomic regions of Mycobacterium leprae | journal = Microbial Pathogenesis | volume = 47 | issue = 3 | pages = 183–187 | date = September 2009 | pmid = 19555754 | doi = 10.1016/j.micpath.2009.06.006 }}</ref>  This genome reduction is not complete.<ref name="pmid31152726">{{cite journal | vauthors = Chavarro-Portillo B, Soto CY, Guerrero MI | title = Mycobacterium leprae's evolution and environmental adaptation | journal = Acta Tropica | volume = 197 | issue =  | pages = 105041 | date = September 2019 | pmid = 31152726 | doi = 10.1016/j.actatropica.2019.105041 | s2cid = 173188912 }}</ref> 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.

=== Essential enzymes ===
There are eight essential enzymes for ''Mycobacterium leprae'', and one of them is [[alanine racemase]] (alr). This enzyme is significant because it is found in [[D-alanine—D-alanine ligase]] and [[alanine]]/Aspartate metabolism. Other essential enzymes include putative [[DTDP-4-dehydrorhamnose 3,5-epimerase|dTDP4deydrorhamnose]] 3, 5epimerase (rm1C) which plays an important role in both Nucleotide sugar metabolism and polyketide sugar unit biosynthesis. Petidoglycan biosynthesis also require murG, murF, MurE, murY, murC, and murD, the remaining six essential enzymes for ''mycobacterium leprae.'' <ref>{{Cite journal |last1=Shanmugam |first1=Anusuya |last2=Natarajan |first2=Jeyakumar |date=2010-03-31 |title=Computational genome analyses of metabolic enzymes in Mycobacterium leprae for drug target identification |journal=Bioinformation |volume=4 |issue=9 |pages=392–395 |doi=10.6026/97320630004392 |issn=0973-2063 |pmc=2951640 |pmid=20975887}}</ref>{{better source needed|date=August 2023}}

== Distribution ==
{{Further|Epidemiology of leprosy}}

The bacterium has a global distribution in humans but the highest prevalence is in sub-Saharan Africa, Asia and South America.<ref name="pmid26441080">{{cite journal | vauthors = Reibel F, Chauffour A, Brossier F, Jarlier V, Cambau E, Aubry A | title = New Insights into the Geographic Distribution of Mycobacterium leprae SNP Genotypes Determined for Isolates from Leprosy Cases Diagnosed in Metropolitan France and French Territories | journal = PLOS Neglected Tropical Diseases | volume = 9 | issue = 10 | pages = e0004141 | date = 2015 | pmid = 26441080 | pmc = 4595418 | doi = 10.1371/journal.pntd.0004141 | doi-access = free }}</ref> The geographic occurrences of ''Mycobacterium leprae'' include: Angola, Brazil, Central African Republic, the Democratic Republic of Congo, Federated States of Micronesia, India, Kiribati, Madagascar, Nepal, Republic of Marshall Islands, and the United Republic of Tanzania.<ref>{{Cite web|title = Risk of Exposure {{!}} Hansen's Disease (Leprosy) {{!}} CDC|url = https://www.cdc.gov/leprosy/exposure/index.html|website = www.cdc.gov|access-date = 2015-11-17|archive-date = July 19, 2017|archive-url = https://web.archive.org/web/20170719140802/https://www.cdc.gov/leprosy/exposure/index.html|url-status = live}}</ref>

Since the introduction of multidrug therapy (MDT) in the 1980s, the prevalence of leprosy cases has declined by 95%.<ref name="pmid34038422">{{cite journal |vauthors=Hambridge T, Nanjan Chandran SL, Geluk A, Saunderson P, Richardus JH |title=Mycobacterium leprae transmission characteristics during the declining stages of leprosy incidence: A systematic review |journal=PLOS Neglected Tropical Diseases |volume=15 |issue=5 |pages=e0009436 |date=May 2021 |pmid=34038422 |pmc=8186771 |doi=10.1371/journal.pntd.0009436 |url= |doi-access=free }}</ref> This decline led the World Health Organization (WHO) to declare leprosy eliminated as a public health problem, defined as a prevalence of less than one leprosy patient per 10,000 population.<ref name="pmid25905706">{{cite journal |vauthors=Smith WC, van Brakel W, Gillis T, Saunderson P, Richardus JH |title=The missing millions: a threat to the elimination of leprosy |journal=PLOS Neglected Tropical Diseases |volume=9 |issue=4 |pages=e0003658 |date=April 2015 |pmid=25905706 |pmc=4408099 |doi=10.1371/journal.pntd.0003658 |url= |doi-access=free }}</ref>  Aside from ''Mycobacterium leprae'' transmission from infected humans, environmental sources could also be an important reservoir.  ''Mycobacterium leprae'' DNA was detected in soil from houses of leprosy patients in Bangladesh, armadillos' holes in Suriname and habitats of lepromatous red squirrels in the British Isles.<ref name="pmid30816338">{{cite journal |vauthors=Tió-Coma M, Wijnands T, Pierneef L, Schilling AK, Alam K, Roy JC, Faber WR, Menke H, Pieters T, Stevenson K, Richardus JH, Geluk A |title=Detection of Mycobacterium leprae DNA in soil: multiple needles in the haystack |journal=Scientific Reports |volume=9 |issue=1 |pages=3165 |date=February 2019 |pmid=30816338 |pmc=6395756 |doi=10.1038/s41598-019-39746-6 |bibcode=2019NatSR...9.3165T |url=}}</ref> One study found numerous reports of leprosy cases with a history of contact with armadillos in the United States.<ref name="pmid34038422"/> A zoonotic transmission pathway from exposure to armadillos has been proposed, with human patients from a previous study in southeastern United States shown to be infected with the same armadillo-associated ''Mycobacterium leprae'' genotype.<ref name="pmid26583204">{{cite journal |vauthors=Sharma R, Singh P, Loughry WJ, Lockhart JM, Inman WB, Duthie MS, Pena MT, Marcos LA, Scollard DM, Cole ST, Truman RW |title=Zoonotic Leprosy in the Southeastern United States |journal=Emerging Infectious Diseases |volume=21 |issue=12 |pages=2127–34 |date=December 2015 |pmid=26583204 |pmc=4672434 |doi=10.3201/eid2112.150501 |url=}}</ref> High rates of ''Mycobacterium leprae'' infection were observed in armadillos in the Brazilian state of Pará, and individuals who frequently consumed armadillo meat showed a significantly higher titres of the M. leprae-specific antigen, phenolic glycolipid I (PGL-I) compared with those who did not or ate them less frequently.<ref name="pmid29953440">{{cite journal |vauthors=da Silva MB, Portela JM, Li W, Jackson M, Gonzalez-Juarrero M, Hidalgo AS, Belisle JT, Bouth RC, Gobbo AR, Barreto JG, Minervino AH, Cole ST, Avanzi C, Busso P, Frade MA, Geluk A, Salgado CG, Spencer JS |title=Evidence of zoonotic leprosy in Pará, Brazilian Amazon, and risks associated with human contact or consumption of armadillos |journal=PLOS Neglected Tropical Diseases |volume=12 |issue=6 |pages=e0006532 |date=June 2018 |pmid=29953440 |pmc=6023134 |doi=10.1371/journal.pntd.0006532 |url= |doi-access=free }}</ref><ref name="pmid34038422"/>

== Evolution ==
The closest relative to ''Mycobacterium leprae'' is ''Mycobacterium lepromatosis''. These species diverged {{Ma|13.9}} (95% highest [[Credible interval|posterior density]] {{Ma|8.2}} – {{Ma|21.4}} ) The [[most recent common ancestor]] of the extant ''Mycobacterium leprae'' strains was calculated to have lived 3,607 years ago (95% highest posterior density 2204–5525 years ago). The estimated substitution rate was 7.67 x 10<sup>−9</sup> substitutions per site per year, similar to other bacteria.<ref name=Singh2015>{{cite journal | vauthors = Singh P, Benjak A, Schuenemann VJ, Herbig A, Avanzi C, Busso P, Nieselt K, Krause J, Vera-Cabrera L, Cole ST | display-authors = 6 | title = Insight into the evolution and origin of leprosy bacilli from the genome sequence of Mycobacterium lepromatosis | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 112 | issue = 14 | pages = 4459–4464 | date = April 2015 | pmid = 25831531 | pmc = 4394283 | doi = 10.1073/pnas.1421504112 | doi-access = free | bibcode = 2015PNAS..112.4459S }}</ref>

A study of genomes isolated from medieval cases estimated the mutation rate to be 6.13 × 10<sup>−9</sup>. The authors also showed that the leprosy bacillus in the Americas was brought there from Europe.<ref name="Schuenemann_2013"/> Another study suggests that ''Mycobacterium leprae'' originated in East Africa and spread from there to Europe and the [[Middle East]] initially before spreading to West Africa and the [[Americas]] in the last 500 years.<ref name=Monot2015>{{cite journal | vauthors = Monot M, Honoré N, Garnier T, Araoz R, Coppée JY, Lacroix C, Sow S, Spencer JS, Truman RW, Williams DL, Gelber R, Virmond M, Flageul B, Cho SN, Ji B, Paniz-Mondolfi A, Convit J, Young S, Fine PE, Rasolofo V, Brennan PJ, Cole ST | display-authors = 6 | title = On the origin of leprosy | journal = Science | volume = 308 | issue = 5724 | pages = 1040–1042 | date = May 2005 | pmid = 15894530 | doi = 10.1126/science/1109759 | url = https://hal-pasteur.archives-ouvertes.fr/pasteur-00204117/document | access-date = July 14, 2019 | url-status = live | s2cid = 86109194 | archive-url = https://web.archive.org/web/20200803145549/https://hal-pasteur.archives-ouvertes.fr/pasteur-00204117/document | archive-date = August 3, 2020 }}</ref>

Almost complete sequences of ''Mycobacterium 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]]. 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 its evolution and course through history, phylogeography of the leprosy bacillus, and the disappearance of leprosy from Europe.<ref name=Schuenemann_2013/>

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 loss of virulence, but due to extraneous factors, such as other infectious diseases, changes in host immunity, or improved social conditions.<ref name=Schuenemann_2013>{{cite journal | vauthors = Schuenemann VJ, Singh P, Mendum TA, Krause-Kyora B, Jäger G, Bos KI, Herbig A, Economou C, Benjak A, Busso P, Nebel A, Boldsen JL, Kjellström A, Wu H, Stewart GR, Taylor GM, Bauer P, Lee OY, Wu HH, Minnikin DE, Besra GS, Tucker K, Roffey S, Sow SO, Cole ST, Nieselt K, Krause J | display-authors = 6 | title = Genome-wide comparison of medieval and modern Mycobacterium leprae | journal = Science | volume = 341 | issue = 6142 | pages = 179–183 | date = July 2013 | pmid = 23765279 | doi = 10.1126/science.1238286 | s2cid = 22760148 | bibcode = 2013Sci...341..179S }}</ref>

== Pathogenesis ==
{{Main|Leprosy}}
The incubation period of ''Mycobacterium leprae'' ranges from 9 months to 20 years.<ref>{{Cite web|title = Leprosy (Hansen's disease) – Blue Book – Department of Health and Human services, Victoria, Australia|url = http://ideas.health.vic.gov.au/bluebook/leprosy.asp#incubation|website = ideas.health.vic.gov.au|access-date = 2015-11-17|language = en-AU|archive-date = November 8, 2015|archive-url = https://web.archive.org/web/20151108021843/http://ideas.health.vic.gov.au/bluebook/leprosy.asp#incubation|url-status = live}}</ref> The bacterium replicates intracellularly inside [[histiocyte]]s and nerve cells and has two forms. One form is "tuberculoid", which induces a cell-mediated response that limits its growth, and has few detectible bacilli (paucibacillary).<ref name=":1">{{cite journal | vauthors = Hess S, Rambukkana A | title = Cell Biology of Intracellular Adaptation of ''Mycobacterium leprae'' in the Peripheral Nervous System | journal = Microbiology Spectrum | volume = 7 | issue = 4 | pages = 7.4.13 | date = July 2019 | pmid = 31322104 | pmc = 6700727 | doi = 10.1128/microbiolspec.BAI-0020-2019 | veditors = Cossart P, Roy CR, Sansonetti P }}</ref> Through this form, ''Mycobacterium leprae'' multiplies at the site of entry, usually the skin, invading and colonizing [[Schwann cells]]. The bacterium then induces T-helper lymphocytes, epithelioid 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.<ref name="pmid34672479"/>
[[File:Nine-banded-Armadillo.jpg|thumb|Nine-Banded-Armadillo, which is a known carrier of leprosy<ref name="pmid35722339">{{cite journal |vauthors=Cabral N, de Figueiredo V, Gandini M, de Souza CF, Medeiros RA, Lery LM, Lara FA, de Macedo CS, Pessolani MC, Pereira GM |title=Modulation of the Response to Mycobacterium leprae and Pathogenesis of Leprosy |journal=Frontiers in Microbiology |volume=13 |issue= |pages=918009 |date=2022 |pmid=35722339 |pmc=9201476 |doi=10.3389/fmicb.2022.918009 |doi-access=free }}</ref>]] The second form of leprosy is the "lepromatous" form, in which the microbes proliferate within the macrophages at the site of entry, and has many detectable bacilli (multibacillary).<ref name=":1" /> They also grow within the epithelial tissues of the face and ear lobes. The [[Suppressor T cells|suppressor T-cells]] that are induced are numerous, but the epithelioid and [[giant cell]]s are rare or absent. With cell-mediated immunity impaired, large numbers of ''Mycobacterium 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 [[Leonine facies|lion face]]". Extensive penetration by this bacterium may lead to severe body damage; for example the loss of bones, fingers, and toes.<ref name="pmid34672479">{{cite journal | vauthors = Frade MA, Coltro PS, Filho FB, Horácio GS, Neto AA, da Silva VZ, Westin AT, Guimarães FR, Innocentini LM, Motta AC, Farina JA | display-authors = 6 | title = Lucio's phenomenon: A systematic literature review of definition, clinical features, histopathogenesis and management | journal = Indian Journal of Dermatology, Venereology and Leprology | volume = 88 | issue = 4 | pages = 464–477 | date = 2022 | pmid = 34672479 | doi = 10.25259/IJDVL_909_19 | s2cid = 239051859 | doi-access = free }}</ref>

== Symptoms of a ''Mycobacterium leprae'' infection ==
The symptoms of a ''Mycobacterium leprae'' infection, also known as leprosy, are skin sores that are pale in color, lumps or bumps that do not go away after several weeks or months, nerve damage which can lead to complications with the ability to sense feeling in the arms and legs as well as muscle weakness. Symptoms usually take 3–5 years from being exposed to manifest within the body. However, some individuals do not begin to show symptoms until 20 years after exposure to the disease. This long incubation period makes the ability to properly be able to diagnose when an individual came into contact with the disease very difficult.<ref>{{Cite web|url=https://www.webmd.com/skin-problems-and-treatments/guide/leprosy-symptoms-treatments-history#1-3|title=Leprosy Overview|website=WebMD|access-date=November 14, 2019|archive-date=May 27, 2018|archive-url=https://web.archive.org/web/20180527225028/https://www.webmd.com/skin-problems-and-treatments/guide/leprosy-symptoms-treatments-history#1-3|url-status=live}}</ref>

In armadillos, ''Mycobacterium leprae'' causes a  disseminated infection with similar structural and pathological changes in tissues and nerves.<ref name="pmid31531622">{{cite journal | vauthors = Oliveira IV, Deps PD, Antunes JM | title = Armadillos and leprosy: from infection to biological model | journal = Revista do Instituto de Medicina Tropical de Sao Paulo | volume = 61 | issue =  | pages = e44 | date = September 2019 | pmid = 31531622 | pmc = 6746198 | doi = 10.1590/S1678-9946201961044 }}</ref>

In squirrels, according the to Veterinary Pathology Unit of the  [[University of Edinburgh]], " The disease is unmistakeable: there is gross swelling and loss of hair around the snout, lips, eyelids, ears, genitalia and sometimes feet and lower limbs. This bare skin has a "shiny" appearance. The squirrel is usually in generally poor body condition and may have a heavy burden of parasites like fleas, ticks and mites."<ref>[https://scottishsquirrels.org.uk/wp-content/uploads/2019/09/Red-Squirrel-Leprosy.pdf Red squirrel leprosy, The University of Edinburgh]</ref>
[[File:Dapsone.svg|thumb|Chemical structure of [[Dapsone]], the first effective antibiotic for the treatment of leprosy, discovered in the 1940s]]

== Treatment ==
The [[mycolic acid]]s in the bacteria's cell walls afford resistance to many antibiotics and are a major virulence factor.<ref name="pmid34216933">{{cite journal |vauthors=Biegas KJ, Swarts BM |title=Chemical probes for tagging mycobacterial lipids |journal=Current Opinion in Chemical Biology |volume=65 |issue= |pages=57–65 |date=December 2021 |pmid=34216933 |doi=10.1016/j.cbpa.2021.05.009|doi-access=free }}</ref> Multidrug therapy (MDT) was recommended by WHO Expert Committee in 1984, and became the standard leprosy treatment. MDT has been supplied by WHO for free since 1995 to endemic countries. MDT is used to treat leprosy because treatment of leprosy with one drug (monotherapy) can result in drug resistance. The drug combination used in MDT will depend on the classification of the disease. WHO recommends patients with multibacillary leprosy use a combination of Rifampicin, Clofazimine, and Dapsone for 12 months. WHO recommends patients with paulibacilalry leprosy use combination of Rifampicin and Dapsone for a duration of 6 months.<ref>World Health Organization. "Guidelines for the diagnosis, treatment and prevention of leprosy." (2018).</ref> Antibiotics must be taken regularly until treatment is complete because ''Mycobacterium leprae'' can become drug resistant.<ref name=":0">{{Cite web|url=https://www.cdc.gov/leprosy/treatment/index.html|title=Diagnosis and Treatment {{!}} Hansen's Disease (Leprosy) {{!}} CDC|date=2018-11-02|website=www.cdc.gov|language=en-us|access-date=2019-11-12|archive-date=November 8, 2019|archive-url=https://web.archive.org/web/20191108155324/https://www.cdc.gov/leprosy/treatment/index.html|url-status=live}}</ref> Effectiveness of the treatment can be determined with the use of an acid-fast stain of ''Mycobacterium leprae'' from a skin smear to estimate the number of bacilli still present in the patient.<ref>Lahiri R, Adams LB. 18 September 2016, posting date. Cultivation and viability determination of ''Mycobacterium leprae'', Chapter 5.3. ''In'' Scollard DM, Gillis TP (ed), International textbook of leprosy. www.internationaltextbookofleprosy.org.</ref>

The number of reported cases of leprosy annually is around 250,000 cases indicating that the chain of transmission has yet to be broken despite the use of MDT leading to a 90% reduction in the prevalence rate of leprosy. This makes it very evident that control of the disease is not yet where it needs to be calling for the need in continued research towards treatment and control.<ref name="pmid21162636" />

A preventive measure of ''Mycobacterium leprae'' is to avoid close contact with infectious people who are untreated.<ref>{{Cite web|title = Leprosy: MedlinePlus Medical Encyclopedia|url = https://www.nlm.nih.gov/medlineplus/ency/article/001347.htm|website = www.nlm.nih.gov|access-date = 2015-11-17|archive-date = October 6, 2015|archive-url = https://web.archive.org/web/20151006121208/https://www.nlm.nih.gov/medlineplus/ency/article/001347.htm|url-status = live}}</ref> Blindness, crippling of the hands and feet, and paralysis are all effects of nerve damage associated with untreated ''M. leprae.'' Treatment does not reverse the nerve damage done, which is why early treatment is needed.<ref name=":0" /> The [[Bacillus Calmette-Guérin|Bacillus Calmette–Guérin]] vaccine offers a variable amount of protection against leprosy in addition to its main target of [[tuberculosis]].<ref>{{cite journal | vauthors = Duthie MS, Gillis TP, Reed SG | title = Advances and hurdles on the way toward a leprosy vaccine | journal = Human Vaccines | volume = 7 | issue = 11 | pages = 1172–1183 | date = November 2011 | pmid = 22048122 | pmc = 3323495 | doi = 10.4161/hv.7.11.16848 }}</ref>

=== Targets of antibiotics ===
Dapsone competitively inhibits the enzyme dihydropteroate synthase (DHPS) resulting in decreases the production of tetrahydrofolate, which is an essential component of nucleic acid biosynthesis in ''M. leprae.'' Rifampin will interrupt binding of the β-subunit  of the DNA-dependent RNA polymerase, which will uncouple mRNA production and results in cell death. Clofazimine's mechanisms are not fully understood regarding ''Mycobacterium leprae'', but the drug's binding appear to occur at base sequences with guanine, which may explain why clofazimine has a preference for G+C rich genomes of mycobacteria over human DNA. The binding of clofazimine to mycobacterial DNA can has been proven as weakly bactericidal against ''Mycobacterium leprae'' in mice, which is why it is not suitable for single drug therapy for leprosy. Out of the three main drugs rifampin is more bactericidal than either dapsone or clofazimine.<ref>Cambau E, Williams DL. 25 January 2019, posting date. Anti-leprosy drugs: Modes of action and mechanisms of resistance in ''Mycobacterium leprae'', Chapter 5.2. ''In'' Scollard DM, Gillis TP (ed), International textbook of leprosy. www.internationaltextbookofleprosy.org.</ref>

=== Potential antibiotic targets ===
It is important to find new targets for antibiotics due to increasing  resistance. ''Mycobacterium leprae'' has six essential enzymes murC, murD, murE, murF, murG, and murY that are all essential for [[peptidoglycan]] biosynthesis in ''M. leprae.'' These enzymes and peptidoglycan biosynthesis are potential  targets for antibiotics. By targeting these enzymes, which catalyze additions of short polypeptide chains, synthesis of the bacterial cell wall can be prevented.<ref>{{Cite journal |title=Computational genome analyses of metabolic enzymes in Mycobacterium leprae for drug target identification |url=http://www.bioinformation.net/004/008200042010.htm |access-date=2022-11-17 |journal=Bioinformation |year=2010 |doi=10.6026/97320630004392 |pmc=2951640 |pmid=20975887|last1=Shanmugam |first1=Anusuya |last2=Natarajan |first2=Jeyakumar |volume=4 |issue=9 |pages=392–395 }}</ref>{{better source needed|date=August 2023}}

===Antibiotic resistance ===
Resistance to antibiotics is seen in around 10% of new cases of leprosy and in around 15% of relapsed cases.<ref name="pmid36293307">{{cite journal |vauthors=Li X, Li G, Yang J, Jin G, Shao Y, Li Y, Wei P, Zhang L |title=Drug Resistance (Dapsone, Rifampicin, Ofloxacin) and Resistance-Related Gene Mutation Features in Leprosy Patients: A Systematic Review and Meta-Analysis |journal=International Journal of Molecular Sciences |volume=23 |issue=20 |date=October 2022 |page=12443 |pmid=36293307 |pmc=9604410 |doi=10.3390/ijms232012443|doi-access=free }}</ref>
Drug resistance in ''Mycobacterium leprae'' is thought  to be from genetic alterations in the antibiotic targets and a reduction in cell wall permeability.<ref name=":5">{{cite journal | vauthors = Machado D, Lecorche E, Mougari F, Cambau E, Viveiros M | title = Insights on ''Mycobacterium leprae'' Efflux Pumps and Their Implications in Drug Resistance and Virulence | journal = Frontiers in Microbiology | volume = 9 | pages = 3072 | date = 2018 | pmid = 30619157 | pmc = 6300501 | doi = 10.3389/fmicb.2018.03072 | doi-access = free }}</ref>  Compared to the amount of [[efflux pump]]s in ''[[Mycobacterium tuberculosis|M. tuberculosis]], Mycobacterium leprae'' contains about half as many. The efflux pumps contributing to drug resistance and virulence in ''[[Mycobacterium tuberculosis|M. tuberculosis]]'' have been retained throughout the genome reductive evolution that ''Mycobacterium leprae'' underwent.<ref name=":5" />

== Discovery ==
[[File:Gerhard Armauer Hansen. Photomechanical print. Wellcome V0026512.jpg|thumb|[[Gerhard Armauer Hansen]] (1841–1912), who first discovered ''Mycobacterium leprae'' in 1873]]
''Mycobacterium leprae''  was discovered in 1873 by the Norwegian physician [[Gerhard Armauer Hansen]] (1841–1912), and was the first bacterium to be identified as a cause of disease in humans.<ref name="Hansen_1874">{{cite book | vauthors = Hansen GA |author-link1=Gerhard Armauer Hansen |year=1874 |title=Undersøgelser Angående Spedalskhedens Årsager |trans-title=Investigations concerning the etiology of leprosy | language = Danish |oclc=969496922 |url=https://wellcomelibrary.org/item/b28042098 |access-date=April 9, 2021 |archive-date=September 29, 2022 |archive-url= https://web.archive.org/web/20220929021454/https://wellcomecollection.org/works/eg92q4me |url-status=live }}</ref> It was confirmed to be a bacterium by [[Albert Ludwig Sigesmund Neisser]] who argued with Hansen
over priority for the discovery.<ref name="pmid33526747">{{cite journal | vauthors = Bieliaieva O, Uvarkina O, Lysanets Y, Morokhovets H, Honcharova Y, Melaschenko M | title = Gerhard Hansen Vs. Albert Neisser: Priority For the invention of Mycobacterium Leprae and problems of bioethics | journal = Georgian Medical News | volume =  | issue = 309 | pages = 156–1161 | date = December 2020 | pmid = 33526747 | doi =  }}</ref> Hansen's attempts to infect animals with the bacteria were unsuccessful. When, in 1879, he injected, without consent, tissue from a person with lepromatous leprosy into the eye of 33-year old Kari Nielsdatter who had the milder tuberculoid form of the infection, he was dismissed from his post at the Leprosy Hospital in Bergen and was banned from practising medicine.<ref>{{cite book | vauthors = Dobson MJ |title=Disease |publisher=Quercus |page =25|location=Englewood Cliffs, N.J |year=2008 |isbn=978-1-84724-399-7}}</ref>  The case had little effect on Hansen's professional reputation, and he continued with his research.<ref>{{cite web |url= https://worldneurologyonline.com/article/armauer-hansen-the-controversy-surrounding-his-unethical-human-to-human-leprosy-transmission-experiment/|title=Armauer Hansen: The Controversy Surrounding his Unethical Human-to-Human Leprosy Transmission Experiment| vauthors = Lanska DJ |year=2015 |access-date=2020-10-30}}</ref>

==Notes==
{{Notelist}}{{clear}}

== References ==
{{Reflist}}

== External links ==
{{Scholia|topic}}
* [http://www.sanger.ac.uk/Projects/M_leprae The genome of ''Mycobacterium leprae'']
* {{cite web |title=''Mycobacterium leprae'' |work=NCBI Taxonomy Browser |url=https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=1769 |id=1769}}

{{Gram-positive actinobacteria diseases|state=collapsed}}
{{Taxonbar|from=Q155891}}
{{Authority control}}

[[Category:Acid-fast bacilli]]
[[Category:Leprosy]]
[[Category:Mycobacteria|leprae]]
[[Category:Bacteria described in 1874]]
[[Category:Pathogenic bacteria]]