Mycobacterium avium complex

A Microbial Biorealm page on the genus Mycobacterium avium complex

Classification

Higher order taxa

Bacteria (domain); Actinobacteria (phylum); Actinobacteria (class); Actinobacteridae (subclass); Actinomycetales (order); Corynebacterineae (suborder); Mycobacteriaceae (family); Mycobacterium (genus); Mycobacterium avium complex (MAC) (species group).

Species

Includes: Mycobacterium avium

Mycobacterium intracellulare

Also known by: Mycobacterium avium intracelluare (MAI)

NCBI: Taxonomy

Description and significance

Mycobacterium avium complex (MAC) contains 28 serovars of two species of mycobacteria: Mycobacterium avium and Mycobacterium intracellulare. These bacterias are slow-growing and cause opportunistic infections to animals, and immunosuppressed humans. MAC is prevalent in the environment. They are found everywhere from fresh to saltwater and even in cigarette (7). This complex commonly formed biofilms in places abundant with water, food, and soil. They are notorious for being highly resistant to many antibiotics as well as disinfectant and bleach, including Chlorine (10). The biofilms were detected by the use of crystal violet staining and optic and electron microscopy (3). They are usually distinguished by a smooth, wet surface. Biofilms have many negative effects on humans. The colonies of these different bacterial cells inside our bodies protect them from being attack by our immune system. They can develop in our bodies from the surfaces of medical implants such as urinary catheter or in the cracks of our teeth to form plaque. These bacterias also exist in water and oil pipelines, which slow and even clogged the flow of fluid (6). MAC biofilms are also believed to be essential to the survival of virulent strains. Although, the impact of biofilm is clearly evident, how MAC biofilm form remains a mystery to mankind. All that is known is that its formation is dependent on the quantity of calcium, zinc (II), and magnesium(3). Regardless of the limited information, studies are being done to identify genes of M. avium that are essential in their biofilm formation, with the hope that this information will prevent the bacterial colonization of these MAC biofilms (3).

Genome structure

Mycobacterium avium was completely sequenced on 11/29/2006 at the J. Craig Venter Institute. Its entire genome consists of 5,475,491 nucleotides long, with a GC (guanine cytosine) content of 68% and 32% for AT (adenine thymine). Guanine and cytosine are paired with each other by three hydrogen bonds, whereas adenine and thymine have 2 hydrogen bonds that bring them together. Because of the larger number of hydrogen bonds, guanine and cytosine are pulled stronger together, and it would take more energy and a higher melting temperature to separate the two. To determine the DNA genome within a cell, scientists use restriction endonuclease to cleave DNA into many small fragments. The endonucleases usually cleave at an AT rich, because two hydrogen bonds are weaker and require less energy to pull apart than three bonds. In the Mycobacterium avium, approximately 88% of its genome are coding regions for 5120 proteins. Commonly found in MAC are extrachromosomal DNA in the form of self-replicating plasmids. Studies are being done to determine the significance of plasmids in a M. avium strain (6).

Cell structure and metabolism

Mycobacterium avium are acid fast bacillus. They are characterized by a thin cell wall covalently attached to the long chain of hydrocarbons called mycolic acid. This complex between the peptidoglycan and mycolic acids creates the waxy hydrophobic surface of the cell, which greatly restricts the transport of many compounds into and out of the cell, and eventually slows down growth. Because of its high hydrophobicity due to the waxy outer layer, many soluble antibiotic drugs cannot cross the membrane and attack the pathogen. Therefore, Mycobacterium avium are extremely resistant to many chemotherapeutic agents as well as many cleaning products, leaving only a limited number of drugs that these bacteria are fairly susceptible to. When taking drugs to treat MAC infection, it is usually accompanied by a special agent or detergent to break down the waxy layer and allowing the drug to penetrate into the cell. Mycobacteria also have a lipopolysaccharide (LPS) anchored into the plasma membrane of the cell with the carbohydrate chain sticking out of the cell (6).

Little information is known about the process of biosynthesis and breakdown for this complex of organisms. What is known is that these organisms undergo aerobic respiration, requiring them to find a way to get oxygen, either through their hosts or in the environments. They use palmitic and oleic acids as their main carbon and energy source. Palmitate and oleate are long chain fatty acids that could later be incorporated into the hydrophobic surface of the cell that is characteristic of acid-fast mycobacteria.

Ecology

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

Pathology

Mycobacterium avium complex disease occurs in persons with defects in their cellular immunity, which cause disseminated infection in humans with suppressed immune system, such as those suffering from AIDS, whose CD4 cell counts are well below 50 cells per microliter. The modes of transmission are usually through ingestion or inhalation which goes through the respiratory and GI tract. These bacteria cross the bronchial and intestinal tissue to get into our bloodstream. From there, the bacterias enter the bloodstream and spread throughout the body. The symptoms associated with MAC for those with HIV positive includes fever, night sweat, weight loss, abdominal pain, fatigue, diarrhea, and anemia- all occurring excessively. For people who are HIV negative, the greatest risk with MAC is lymadenopathy or it could lead to pulmonary disease. These bacterias have unique, antigenic lipids called glycopeptidolipids (GPLs) which are located on the surface of the cell. The lipids are able to suppressed the immune response of the host and can produce cytokines that will change the way the host reacts to pathogens.

In terms of treatment, MAC is resistant to many chemotherapeutic agents. The limited list of antimycobacterial drugs that they are susceptible to are clarithromycin, azithromycin, ethambutol, clofazimine, and rifamycins (rifabutin). It is treated for a minimal period of 12 months with multi-drug therapy to prevent bacterial resistance to one particular drug (8). However, studies are still undergoing to come up with new drugs as well as to find the regimen of drugs that will be most effective for eradicating the bacterias (9).

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.http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=1764&lvl=3&p=mapview&p=has_linkout&p=blast_url&p=genome_blast&lin=f&keep=1&srchmode=1&unlock 2.Freeman, R., Geier, H., Weigel, K., Do, J., Ford, T., Cangelosi, G. “Roles of Cell Wall Glycopeptidolipid in Surface Adherence and Planktonic Dispersal of Mycobacterium avium”. Applied and Environmental Microbiology. 2006. Volume 72. p. 7554-7558. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1694245 3.Carter, G., Wu, M., Drummond, D., Bermudez, L. “Characterization of Biofilm Formation By Clinical Isolates of Mycobacterium avium”. Journal of Medical Microbiology. 2003. Volume 52. p. 747-752. http://jmm.sgmjournals.org/cgi/content/full/52/9/747 4.http://www.ncbi.nlm.nih.gov/sites/entrez?Db=genome&Cmd=ShowDetailView&TermToSearch=20086 5.Netting, J. “Scientists are Beginning to Understand How Bacteria Find Strength in Numbers”. Science News. 2001. Volume 160. p. 28. http://www.sciencenews.org/articles/20010714/bob12.asp 6.Inderlied, C., Kemper, C., Bermudez, L. “The Mycobacterium avium Complex”. Clinical Microbiology Reviews. 1993. Volume 6. p. 266-310. http://www.pubmedcentral.nih.gov/pagerender.fcgi?artid=358286&pageindex=7#page 7.Chatterjee, D., Khoo, KH. “The Surface Glycopeptidolipids of Mycobacteria: Structures and Biological Properties”. Cellular and Molecular Life Science. 2001. Volume 14. p. 2018-2042. http://www.ncbi.nlm.nih.gov/sites/entrez?db=PubMed&cmd=Retrieve&list_uids=11814054 8.Koirala, J.,Harley, W. “Mycobacterium Avium-Intracellulare”. http://www.emedicine.com/med/topic1532.htm 9.Havlir, D. “Mycobacterium avium Complex: Advances in Therapy”. European Journal of Clinical Microbiology and Infectious Diseases. 1994. Volume 13. p 1435-4373. http://www.springerlink.com/content/l1h0831h47r7336h/?p=72a856958d2149be8144b1d64331f1a3&pi=9 10.Mdluli, K., Swanson, J., Fischer, E., Lee, R., Barry, C. “Mechanisms Involved in the Intrinsic Isoniazid Resistance of Mycobacterium avium”. Molecular Microbiology. 1998. Volume 27. p. 1223-1233. http://www.blackwell-synergy.com/doi/pdf/10.1046/j.1365-2958.1998.00774.x?cookieSet=1

Edited by student of Rachel Larsen