User:Jg98915/Mycobacterium leprae

Lead Section

 * Added: This is likely due to gene deletion and decay that the genome of the species has experienced via reductive evolution.
 * Added: "…and are typically found congregated as a palisade." (9)
 * Changed: "In the past, M. leprae was sensitive to dapsone alone, but since the 1960's, it has developed resistance against the antibiotic, and requires additional measures."
 * Need to add citations for every claim

Diagnosis
- To add: Testing to aid in the diagnosis of leprosy are still needed, but this study attempts to use LID-1 (Leprosy IDRI Diagnostic-1). This is a fusion protein that has been recognized in genome of Mycobacterium leprae as an antigen in diagnostic testing for leprosy.

- To add: Key symptoms that lead to diagnosis of leprosy include hypopigmentation with a loss of sensation, thickened peripheral nerves, and acid-fast staining in slit skin smears.

- To add: The main problem with the identification of leprosy is the lack of sufficient knowledge of early signs of infections by M. leprae. Without enough expertise by clinicians, the cardinal signs are missed and providing confident differential diagnosis will decline.

- To add: "In technologically advanced countries, polymerase chain reaction (PCR) is used to detect M. leprae DNA within hosts. The limitation with this type of testing is that PCR cannot determine if living cells are still residing within the host as DNA can withstand long after the microorganisms has passed. Late diagnosis leads to prolonged transmission and increased risk of damage and disability due to the infection of M. leprae."

Applications

- PCR using 16S

Genome

 * Sentence structure change: Mycobacterium leprae has unique properties among other microbes, such as its lengthy generation time (ranging from 12-14 days), and its inability to be cultured in the laboratory.
 * To add: Mycobacterium leprae has the longest generation time among all other bacteria. (Not sure if this should be added in this section or another)
 * Needs editing: "Comparing the genome sequence of M. leprae with that...contains functional genes." These sentences are awkwardly worded, and may be too specific if they are attempting to give an overview of the subheadings. These details may be more relevant under the subheading "Evolution and pseudogenes"
 * Added: This reductive evolution is largely linked to the organism's development into an obligate intracellular microbe.
 * Added: Due to its reliance on a host organism, many of the species' DNA repair functions have been lost, increasing the occurrence of deletion mutations. Because the products supplied by these deleted genes are typically present in the host cells that M. leprae infects, the impact that the mutations have on the microbe is minimal, allowing for survival within the host despite its reduced genome.

Metabolism
Extensive research has shown that the reductive evolution experienced by the M. leprae genome has impaired its metabolic abilities in comparison to other Mycobacterium, specifically in its catabolic pathways.

Catabolism

 * To add from existing article: "M. leprae has lost the ability to use common carbon sources, such as acetate and galactose causing an inability to generate ATP via the oxidation of NAPH due to the probable impairment of the pathogen's central and energy metabolism pathways. This makes it likely that not only is catabolism for the pathogen is severely limited, but its growth is also restricted to a limited number of carbon sources." [22]

M. leprae’s inability to be grown in axenic media indicates its reliance on nutrients and intermediates from its host. Many of the catabolic pathways present in other Mycobacterium species are compromised, due to the absence enzymes that play key roles in degradation of nutrients. M. leprae has lost the ability to use common carbon sources, such as acetate and galactose, in its central energy metabolism pathways. (22) Additionally, lipid degradation is impaired, with deficits in key lipases, and other proteins involved in lipolysis. Functional carbon catabolic pathways continue to exist in the species, such as the glycolytic pathway, the pentose phosphate pathway, and the TCA cycle. These deficiencies extensively restricts the microbe's growth to a limited number of carbon sources, such as host-derived intermediates. (22)

Anabolism
M. leprae’s anabolic pathways have been largely unaffected by its reductive evolution. 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.

(Maddie)

 * Genome: Article states "The first genome sequence of a strain of M. leprae was completed in 1998." but that was M. tuberculosis. Changed it to "The first genome sequence of a strain of M. leprae was completed in 2001, which revealed only half of the genome contains protein-coding regions and the other half consists of pseudogens and non-coding regions." (citation was included after the article already had the article I found as a reference).


 * Treatment: 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 combination of Rigampicin, Ckifazimine, and Dapsone for 12 months. WHO recommends pateints with paulibacilalry leprosy use combination of Rifampicin and Dapsone for a duration of 6 months. uses combinations of antibiotics that kill M. leprae including: dapsone, rifampin, clofazamine, fluoroquinolones, azithromycin, and minocycline. Antibiotics must be taken regularly until treatment is complete due to the fact M. leprae has the ability to grow back.[26]

(Sydney)

 * https://www.news-medical.net/health/Leprosy-Epidemiology.aspx#:~:text=Leprosy%20is%20a%20chronic%20infectious,in%20the%20majority%20of%20people.
 * tropical countries such as Asia and Africa have the most cases, more specially underdeveloped countries
 * add more specific information in regards to locations globally where cases are most prevalent
 * https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4008049/
 * Added October 27th under Epidemiology Section:
 * Main Article: Epidemiology of leprosy Tropical, more underdeveloped countries are where the greatest number of cases of leprosy are located, more specifically, in countries including but not limited to Brazil, India, and Nepal. Brazil ranks second amongst the most reported cases of leprosy. Leprosy is listed as a public health problem, meaning more than one case per 10,000 inhabitants have been recently reported. Although, recent data has shown that the number of reported cases in Brazil continues to decline specifically in regards to children aged 15 and under. Increased access to patient primary care has shown to correlate to the significant drop in the number of reported cases. Late diagnosis of the disease has still proven to be an issue despite the steady decline in reported cases due to lack of public knowledge regarding the disease and limited access to treatment in certain regions.
 * Added (Nov. 10th) under heading Pseudogenes at the end of the first paragraph: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3076554/
 * Over half of the pathogen's genome is now made up by pseudogenes due to the pathogen undergoing what is known as reductive evolution.
 * added under Treatment 1st paragraph:
 * 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.
 * added at the end of 1st paragraph under Genome:
 * The studying of M. leprae has led researchers to believe that it has lost the ability to utilize common carbon sources, such as acetate and galactose causing an inability to generate ATP via the oxidation of NAPH due to the probable impairment of the pathogen's central and energy metabolism pathways. This makes it likely that not only is catabolism for the pathogen is severely limited, but its growth is also restricted to a limited number of carbon sources.
 * added under Genome
 * Subheading- Essential Enzymes
 * There is a total of eight essential enzymes for M. Leprae, and one of them is Alanine racemase (alr). This enzyme is significant because it is found in DAlanine and Alanine/Aspartate metabolism. Other essential enzymes include Putative 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.

Things to Work On

 * Add Subheadings
 * Metabolism– Julia
 * Taxonomy
 * Antibiotic Resistance? Berkley
 * To add: "Drug resistance in M. leprae is assumed to be from genetic alterations in the antibiotic targets and reduction in cell wall permeability. Research is being conducted to determine whether or not M. leprae utilizes efflux pumps as an antibiotic resistance determinant. When compared to the amount of efflux pumps in M. tuberculosis, Mycobacterium leprae contains about half as many. The efflux pumps contributing to drug resistance and virulence in M. tuberculosis have been retained throughout the genome reductive evolution that M. leprae underwent. These same pumps that extrude drugs from the inside periplasm to the outside of the cell may also contribute to pathogenicity and acquired drug resistance to therapy as was seen in M. tuberculosis.
 * Important Enzymes
 * At the end– Review lead section and ensure everything is summarized