Mycobacterium is a genus of Actinobacteria, given its own family, the Mycobacteriaceae. Over 190 species are recognized in this genus; this genus includes pathogens known to cause serious diseases in mammals, including tuberculosis and leprosy in humans. The Greek prefix myco- means "fungus," alluding to the way mycobacteria have been observed to grow in a mold-like fashion on the surface of cultures, it can not be stained by the Gram stain procedure. Mycobacteria are aerobic, they are bacillary in form, at least in most phases that have attracted human microbiological attention to date. They are nonmotile bacteria, except for the species Mycobacterium marinum, shown to be motile within macrophages, they are characteristically acid-fast. Mycobacteria have an outer membrane, they possess capsules, most do not form endospores. M. marinum and M. bovis have been shown to sporulate. The distinguishing characteristic of all Mycobacterium species is that the cell wall is thicker than in many other bacteria, being hydrophobic and rich in mycolic acids/mycolates.
The cell wall consists of the hydrophobic mycolate layer and a peptidoglycan layer held together by a polysaccharide, arabinogalactan. The cell wall makes a substantial contribution to the hardiness of this genus; the biosynthetic pathways of cell wall components are potential targets for new drugs for tuberculosis. Many Mycobacterium species adapt to growth on simple substrates, using ammonia or amino acids as nitrogen sources and glycerol as a carbon source in the presence of mineral salts. Optimum growth temperatures vary according to the species and range from 25 °C to over 50 °C. Most Mycobacterium species, including most clinically relevant species, can be cultured in blood agar. However, some species grow slowly due to long reproductive cycles — M. leprae, may take more than 20 days to proceed through one division cycle, making laboratory culture a slow process. In addition, the availability of genetic manipulation techniques still lags far behind that of other bacterial species. A natural division occurs between slowly– and rapidly–growing species.
Mycobacteria that form colonies visible to the naked eye within 7 days on subculture are termed rapid growers, while those requiring longer periods are termed slow growers. Some mycobacteria produce carotenoid pigments without light. Others require photoactivation for pigment production. Photochromogens Produce nonpigmented colonies when grown in the dark and pigmented colonies only after exposure to light and reincubation. Ex: M. kansasii, M. marinum, M. simiae. Scotochromogens Produce deep yellow to orange colonies when grown in the presence of either the light or the dark. Ex: M. scrofulaceum, M. gordonae, M. szulgai. Non-chromogens Nonpigmented in the light and dark or have only a pale yellow, buff or tan pigment that does not intensify after light exposure. Ex: M. tuberculosis, M. avium-intra-cellulare, M. bovis, M. ulcerans, M. xenopi Ex: M. fortuitum, M. chelonae Mycobacteria are classical acid-fast organisms. Stains used in evaluation of tissue specimens or microbiological specimens include Fite's stain, Ziehl-Neelsen stain, Kinyoun stain.
Mycobacteria appear phenotypically most related to members of Nocardia and Corynebacterium. Mycobacteria are widespread organisms living in water and food sources. Some, including the tuberculosis and the leprosy organisms, appear to be obligate parasites and are not found as free-living members of the genus. Mycobacteria can colonize their hosts without the hosts showing any adverse signs. For example, billions of people around the world have asymptomatic infections of M. tuberculosis. Mycobacterial infections are notoriously difficult to treat; the organisms are hardy due to their cell wall, neither Gram negative nor positive. In addition, they are resistant to a number of antibiotics that disrupt cell-wall biosynthesis, such as penicillin. Due to their unique cell wall, they can survive long exposure to acids, detergents, oxidative bursts, lysis by complement, many antibiotics. Most mycobacteria are susceptible to the antibiotics clarithromycin and rifamycin, but antibiotic-resistant strains have emerged.
As with other bacterial pathogens, M. tuberculosis produces a number of surface and secreted proteins that contribute to its virulence. However, the mechanism by which these proteins contribute to virulence remains unknown. Mycobacteria can be classified into several major groups for purpose of diagnosis and treatment: M. tuberculosis complex, which can cause tuberculosis: M. tuberculosis, M. bovis, M. africanum, M. microti. Mycosides are phenolic alcohols that were shown to be components of Mycobacterium glycolipids that are termed glycosides of phenolphthiocerol dimycocerosate. Mycosides A and B have 20 carbon atoms, respectively. Comparative analyses of mycobacterial genomes have identified several conserved indels and signature proteins that are uniquely found in all sequenced species from the genus Mycobacterium. Additionally, 14 proteins are found only in the species from the genera Mycobacterium and Nocardia, suggesting that these two
Mycobacterium tuberculosis is a species of pathogenic bacteria in the family Mycobacteriaceae and the causative agent of tuberculosis. First discovered in 1882 by Robert Koch, M. tuberculosis has an unusual, waxy coating on its cell surface due to the presence of mycolic acid. This coating makes the cells impervious to Gram staining, as a result, M. tuberculosis can appear either Gram-negative or Gram-positive. Acid-fast stains such as Ziehl-Neelsen, or fluorescent stains such as auramine are used instead to identify M. tuberculosis with a microscope. The physiology of M. tuberculosis is aerobic and requires high levels of oxygen. A pathogen of the mammalian respiratory system, it infects the lungs; the most used diagnostic methods for tuberculosis are the tuberculin skin test, acid-fast stain and polymerase chain reaction. The M. tuberculosis genome was sequenced in 1998. M. tuberculosis is part of a complex that has at least 9 members: M. tuberculosis sensu stricto, M. africanum, M. canetti, M. bovis, M. caprae, M. microti, M. pinnipedii, M. mungi, M. orygis.
It requires oxygen to grow, does not produce spores, is nonmotile. M. tuberculosis divides every 15–20 hours. This is slow compared with other bacteria, which tend to have division times measured in minutes, it is a small bacillus that can withstand weak disinfectants and can survive in a dry state for weeks. Its unusual cell wall is rich in lipids such as mycolic acid and is responsible for its resistance to desiccation and is a key virulence factor. Other bacteria are identified with a microscope by staining them with Gram stain. However, the mycolic acid in the cell wall of M. tuberculosis does not absorb the stain. Instead, acid-fast stains such as Ziehl-Neelsen stain, or fluorescent stains such as auramine are used. Cells are curved rod-shaped and are seen wrapped together, due to the presence of fatty acids in the cell wall that stick together; this appearance is referred to like strands of cord that make up a rope. M. tuberculosis is characterized in tissue by caseating granulomas containing Langhans giant cells, which have a "horseshoe" pattern of nuclei.
M. tuberculosis can be grown in the laboratory. Compared to other studied bacteria, M. tuberculosis has a remarkably slow growth rate, doubling once per day. Used media include liquids such as Middlebrook 7H9 or 7H12, egg-based solid media such as Lowenstein-Jensen, solid agar-based such as Middlebrook 7H11 or 7H10. Visible colonies require several weeks to grow on agar plates, it is distinguished from other mycobacteria by its production of niacin. Other tests to confirm its identity include gene probes and MALDI-TOF. Humans are the only known reservoirs of M. tuberculosis. A misconception is that M. tuberculosis can be spread by shaking hands, making contact with toilet seats, sharing food or drink, sharing toothbrushes, or kissing. It can only be spread through air droplets originating from a person who has the disease either coughing, speaking, or singing; when in the lungs, M. tuberculosis is phagocytosed by alveolar macrophages, but they are unable to kill and digest the bacterium. Its cell wall prevents the fusion of the phagosome with the lysosome, which contains a host of antibacterial factors.
M. tuberculosis blocks the bridging molecule, early endosomal autoantigen 1. The bacteria multiply unchecked within the macrophage; the bacteria carry the UreC gene, which prevents acidification of the phagosome. In addition, production of the diterpene isotuberculosinol prevents maturation of the phagosome; the bacteria evade macrophage-killing by neutralizing reactive nitrogen intermediates. Protective granulomas are formed due to the production of cytokines and upregulation of proteins involved in recruitment. Granulotomatous lesions are important in both regulating the immune response and minimizing tissue damage. Moreover, T cells help maintain Mycobacterium within the granulomas; the ability to construct M. tuberculosis mutants and test individual gene products for specific functions has advanced the understanding of its pathogenesis and virulence factors. Many secreted and exported proteins are known to be important in pathogenesis. Aerolysin is a virulence factor of the pathogenic bacterium Aeromonas hydrophila.
Resistant strains of M. tuberculosis have developed resistance to more than one TB drug, due to mutations in their genes. Typing of strains is useful in the investigation of tuberculosis outbreaks, because it gives the investigator evidence for or against transmission from person to person. Consider the situation where person A has tuberculosis and believes he acquired it from person B. If the bacteria isolated from each person belong to different types transmission from B to A is definitively disproved; until the early 2000s, M. tuberculosis strains were typed by pulsed field gel electrophoresis. This has now been superseded by variable numbers of tandem repeats, technically easier to perform and allows better discrimination between strains; this method makes use of the presence of repeated DNA sequences within the M. tuberculosis genome. Three generations of VNTR typing for M. tuberculosis are noted. The first scheme, called exact tandem repeat, used only five loci, but the resolution afforded by these five loci was not as good as PFGE.
The second scheme, called mycobacterial interspersed repetitive unit, had discrimination as good as PFGE. The third
Mycobacterium abscessus complex is a group of growing, multidrug-resistant non-tuberculous mycobacteria species that are common soil and water contaminants. Although M. abscessus complex most cause chronic lung infection and skin and soft tissue infection, the complex can cause infection in all human organs in patients with suppressed immune systems. Amongst NTM species responsible for disease, infection caused by M. abscessus complex are more difficult to treat due to antimicrobial drug resistance. M. abscessus cells are gram-positive, acid-fast rods about 1.0–2.5 µm long by 0.5 µm wide. They may form colonies on Löwenstein–Jensen media that appear smooth or rough, white or greyish and nonphotochromogenic. M. abscessus shows growth at 28 °C and 37 °C after 7 days but not at 43 °C. It may grow on MacConkey agar at 28 °C and 37 °C, it shows tolerance to saline media as well as 0.2 % picrate. Strains of the species have been shown to degrade the antibiotic p-aminosalicylate. M. abscessus has been shown to produce arylsulfatase but not of nitrate reductase and Tween 80 hydrolase.
It shows a negative result for the iron uptake test and no utilisation of fructose, oxalate or citrate as sole carbon sources. M. abscessus and M. chelonae can be distinguished from M. fortuitum or M. peregrinum by their failure to reduce nitrate and to take up iron. Tolerance to 5% NaCl in Löwenstein-Jensen media, tolerance to 0.2% picrate in Sauton agar, non-utilisation of citrate as a sole carbon source are characteristics that distinguish M. abscessus from M. chelonae. M. abscessus and M. chelonae sequevar I share an identical sequence in the 54-510 region of 16S rRNA, though both species can be differentiated by their hsp65, ITS or rpoB gene sequences. A draft genome sequence of M. abscessus subsp. Bolletii BDT was completed in 2012. Since a large number of strains from this subspecies have had their genomes sequenced, leading to a clarification of subspecies boundaries. In 1992, M. abscessus was first recognised as a distinct species. In 2006, this group was separated into three subspecies: abscessus and massiliense.
In 2011, massiliense and bolletii were merged into a single subspecies, but were subsequently separated again following greater availability of genome sequence data, which showed the three subspecies formed genetically distinct groups. These distinct groups correspond to important biological differences. Clinically important differences include differing susceptibilities to antibiotics. M. abscessus subsp. Abscessus and bolletii carry a common antibiotic resistance gene which confers resistance to macrolide antibiotics, while massiliense is thought to carry a non-functional copy, is therefore more susceptible to antibiotics and more treated. M. abscessus can cause lung disease, skin infections, central nervous system infections, eye infections, other, less common diseases. Chronic lung disease occurs most in vulnerable hosts with underlying lung disease such as cystic fibrosis and prior tuberculosis. Clinical symptoms of lung infection vary in scope and intensity but include chronic cough with purulent sputum.
Haemoptysis may be present. Systemic symptoms include malaise and weight loss in advance disease; the diagnosis of M. abscessus pulmonary infection requires the presence of symptoms, radiologic abnormalities, microbiologic cultures. M. abscessus can cause skin infections in immunodeficient patients, patients who have undergone surgery, tattooing or acupuncture, or after exposure to hot springs or spas. It can be associated with middle ear infections; the incidence of M. abscessus. Outbreaks of M. abscessus have been reported in clinical settings worldwide. While outbreaks of major clinical concern involve transmission between vulnerable patients such as those receiving lung transplants or being treated for cystic fibrosis, outbreaks have been reported at clinics providing cosmetic surgery, mesotherapy and IV infusion of cell therapy, anthough these are more attributable to contaminated disinfectants and instruments than contact between patients; the type strain of M. abscessus, most referred to as ATCC19977, was isolated in 1953 from a human knee infection presenting with abscess-like lesions, leading to the strain being named "abscessus".
The strain wasn't recognised as a distinct species until 1992, when DNA hybridisation work identified it as genetically distinct from its relative, M. chelonae. The genome of the type train was published in 2009. ATCC 19977 = CCUG 20993 = CIP 104536 = DSM 44196 = JCM 13569 = NCTC 13031 From the Latin ab- + cedere, an abscess is named for the notion that humors leave the body through pus. Mycobacterium abscessus was first isolated from gluteal abscesses in a 62-year-old patient who had injured her knee as a child and had a disseminated infection 48 years later; the species M. bolletii, named after the late microbiologist and taxonomist Claude Bollet, was described in 2006. In current taxonomy, M. bolletii and M. massiliense have been incorporated into M. abscessus subsp. Bolletii. MCAG group This article incorporates public domain text from the CDC as cited Type strain of Mycobacterium abscessus at BacDive - the Bacterial Diversity Metadatabase A guide for patients and clinicians - AIT Therapeutics Mabellini - annotated, modeled structural proteome of Mycobacterium abscessus
Nontuberculous mycobacteria known as environmental mycobacteria, atypical mycobacteria and mycobacteria other than tuberculosis, are mycobacteria which do not cause tuberculosis or leprosy. NTM do cause pulmonary diseases. Mycobacteriosis is any of these illnesses meant to exclude tuberculosis, they occur in many animals, including humans. Mycobacteria are a family of small, rod-shaped bacilli that can be classified into 3 main groups for the purpose of diagnosis and treatment: Mycobacterium tuberculosis complex which can cause tuberculosis: M. tuberculosis, M. bovis, M. africanum, M. microti and M. canetti. M. leprae and M. lepromatosis which cause Hansen's disease called leprosy. Nontuberculous mycobacteria are all the other mycobacteria which can cause pulmonary disease resembling tuberculosis, skin disease, or disseminated disease. Although over 150 different species of NTM have been described, pulmonary infections are most due to Mycobacterium avium complex, Mycobacterium kansasii, Mycobacterium abscessus.
In 1959, botanist Ernest Runyon put these human disease-associated bacteria into four groups: Photochromogens, which develop pigments in or after being exposed to light. Examples include M. simiae and M. marinum. Scotochromogens, which become pigmented in darkness. Examples include M. M. szulgai. Non-chromogens, which includes a group of prevalent opportunistic pathogens called M. avium complex. Other examples are M. xenopi, M. malmoense, M. terrae, M. haemophilum and M. genavense. Rapid growers include four well recognized pathogenic growing non-chromogenic species: M. chelonae, M. abscessus, M. fortuitum and M. peregrinum. Other examples cause disease such as M. smegmatis and M. flavescens. The number of identified and cataloged NTM species has been increasing from about 50 in 1997 to over 125 by January 2007; the surge is due to improved isolation and identification technique. However with these new techniques, the Runyon classification is still sometimes used to organize the mycobacteria into categories.
NTM are distributed in the environment in wet soil, streams and estuaries. Different species of NTM prefer different types of environment. Human disease is believed to be acquired from environmental exposures. Unlike tuberculosis and leprosy, animal-to-human or human-to-human transmission of NTM occurs. NTM diseases have been seen in most industrialized countries, where incidence rates vary from 1.0 to 1.8 cases per 100,000 persons. Recent studies, including one done in Ontario, suggest that incidence is much higher. Pulmonary NTM is estimated by some experts in the field to be at least ten times more common than TB in the U. S. with at least 150,000 cases per year. Most NTM disease cases involve the species known as Mycobacterium avium complex or MAC for short, M. abscessus, M. fortuitum and M. kansasii. M. abscessus is being seen with increasing frequency and is difficult to treat. Mayo Clinic researchers found a three-fold increased incidence of cutaneous NTM infection between 1980 and 2009 in a population-based study of residents of Olmsted County, Minnesota.
The most common species were M. marinum, accounting for 45% of cases and M. chelonae and M. abscessus, together accounting for 32% of patients. M. chelonae infection outbreaks, as a consequence of tattooing with infected ink, have been reported in the United Kingdom and the United States. Growing NTMs are implicated in catheter infections, post-LASIK, skin and soft tissue and pulmonary infections; the most common clinical manifestation of NTM disease is lung disease, but lymphatic, skin/soft tissue, disseminated disease are important. Pulmonary disease caused by NTM is most seen in post-menopausal women and patients with underlying lung disease such as cystic fibrosis and prior tuberculosis, it is not uncommon for alpha 1-antitrypsin deficiency, Marfan syndrome and primary ciliary dyskinesia patients to have pulmonary NTM colonization and/or infection. Pulmonary NTM can be found in individuals with AIDS and malignant disease, it can be caused by many NTM species which depends on region, but most MAC and M. kansasii.
Clinical symptoms vary in scope and intensity but include chronic cough with purulent sputum. Hemoptysis may be present. Systemic symptoms include malaise and weight loss in advanced disease; the diagnosis of M. abscessus pulmonary infection requires the presence of symptoms, radiologic abnormalities, microbiologic cultures. Lymphadenitis can be caused by various species, different from one place to another. Most patient are aged less than 5 years; the disease has a high curability. Soft tissue disease due to NTM infection include post-traumatic abscesses, swimming pool granuloma and Buruli ulcer. Post-traumatic abscesses most occur after injection. Disseminated mycobacterial disease was common in US and European AIDS patients in the 1980s and early 1990s, though the incidence has declined in developed nations since the introduction of active antiretroviral therapy, it can occur in individuals after having renal transplantation. Diagnosis of opportunistic mycobacteria is made by repeated isolation and identification of the pathogen with compatible clinical and radiological features.
Similar to M. tuberculosis, most nontuberculous mycobacteria can be de
Mycobacterium bovis is a slow-growing aerobic bacterium and the causative agent of tuberculosis in cattle. It is related to the bacterium which causes tuberculosis in humans. M. bovis can cause tuberculosis in humans and other mammals. M. bovis is similar in metabolism to M. tuberculosis. M. bovis is a acid-fast, rod-shaped, aerobic bacteria. Unlike M. tuberculosis, M. bovis lacks pyruvate kinase activity, due to pykA containing a point mutation that affects binding of Mg2+ cofactor. Pyruvate kinase catalyses the final step of glycolysis, the dephosphorylation of phosphorenolpyruvate to pyruvate; therefore in M. bovis glycolytic intermediates are unable to enter into oxidative metabolism Although no specific studies have been performed, it seems that M. bovis must rely on amino acids or fatty acids as an alternative carbon source for energy metabolism During the first half of the 20th century, M. bovis is estimated to have been responsible for more losses among farm animals than all other infectious diseases combined.
Infection occurs. M. Bovis is transmitted to humans by consuming raw, infected cows' milk, although it can spread via aerosol droplets. Actual infections in humans are nowadays rare in developed countries because pasteurisation kills M. bovis bacteria in infected milk. In the UK, cattle are tested for the disease as part of an eradication program and culled if they test positive; such cattle can still enter the human food chain, but only after a government veterinary surgeon has inspected the carcass and certified that it is fit for human consumption. However, in areas of the developing world where pasteurisation is not routine, M. bovis is a common cause of human tuberculosis. Bovine tuberculosis is a chronic infectious disease which affects a broad range of mammalian hosts, including humans, deer, pigs, domestic cats, wild carnivores and omnivores; the disease can be transmitted in several ways. M. bovis is the ancestor of the most used vaccine against tuberculosis, M. bovis bacillus Calmette-Guérin.
BCG is a strain, created by growing M. bovis on potato slices soaked in ox-bile and glycerol over a period of 13 years. In New Zealand, the introduced common brushtail possum is a vector for the spread of M. bovis. The Biosecurity Act 1993, which established a national pest-management strategy, is the legislation behind control of the disease in New Zealand; the Animal Health Board operates a nationwide programme of cattle testing and possum control, with the goal of eradicating M. bovis from wild vector species across 2.5 million hectares – or one-quarter – of New Zealand’s at-risk areas, by 2026 and eradicating the disease entirely. The TB-free New Zealand programme is regarded as "world-leading", it has reduced cattle and deer herd infection rates from more than 1700 in 1994 to fewer than 100 herds in July 2011. Much of this success can be attributed to sustained cattle controls reducing cross-infection and breaking the disease cycle. For example, at Hohotaka, in New Zealand's central North Island, control work from 1988 to 1994 achieved a sustained mean reduction of 87.5% in the density of TB‐infected opossums.
As expected, annual TB incidence in local cattle herds declined by a similar amount. Possums are controlled through a combination of trapping, ground-baiting, where other methods are impractical, aerial treatment with 1080 poison. From 1979 to 1984, possum control was stopped due to lack of funding. In spite of regular and frequent TB testing of cattle herds, the number of infected herds snowballed and continued to increase until 1994; the area of New Zealand harbouring TB-infected wild animals expanded from about 10% of the country to 40%. That possums are such effective transmitters of TB appears to be facilitated by their behaviour once they succumb to the disease. Terminally ill TB possums show erratic behaviour, such as venturing out during the daytime to get enough food to eat, seeking out buildings in which to keep warm; as a consequence, they may wander onto paddocks, where they attract the attention of inquisitive cattle and deer. This behaviour has been captured on video. In the 1930s, 40% of cattle in the UK were infected with M. bovis and 50,000 new cases of human M. bovis infection were reported every year.
According to DEFRA and the Health Protection Agency, the risk to people contracting TB from cattle in Great Britain today is low. The HPA has said that three-quarters of the 440 human cases reported to the HPA between 1994 and 2006 were aged 50 years and above and only 44 cases were known to be non-UK born. Badgers were first identified as carriers of M. bovis in 1971, but the report of an independent review committee in 1997 concluded:'strong circumstantial evidence to suggest that badgers represent a significant source of M. bovis infection in cattle... owever, the causal link... has not been proven'. In essence, the contribution of badgers'to the TB problem in British cattle' was at this point a hypothesis that needed to be tested, according to the report; the subsequent Randomised Badger Culling Trial examined this hypothesis by conducting a larg