Mycobacterium tuberculosis

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Mycobacterium tuberculosis
Mycobacterium tuberculosis

Mycobacterium tuberculosis

Department : Actinobacteria
Order : Actinomycetales
Subordination : Corynebacterineae
Family : Mycobacteriaceae
Genre : Mycobacterium
Type : Mycobacterium tuberculosis
Scientific name
Mycobacterium tuberculosis
( Zopf 1883) Lehmann & Neumann 1896
Cultures of Mycobacterium tuberculosis on agar, enlarged

Mycobacterium tuberculosis , also known as tubercle bacillus in German, is a bacterium from the Mycobacteriaceae (mycobacteria) family. It is the major causative agent of tuberculosis in humans. Animals can alsodevelop tuberculosisthrough M. tuberculosis .


M. tuberculosis is a rod-shaped bacterium incapable of active movement. The bacteria are acid-fast and can therefore be differentiated microscopically from non-acid-fast bacteria and other non-acid-fast objects using the Ziehl-Neelsen stain and special fluorescent dye stains (e.g. auramine stain). The bacterial cell wall contains, among other things, arabinogalactan and mycolic acids , which, along with other lipophilic cell wall components, are responsible for acid resistance.

Other characteristic features are its extremely slow growth (15-20 hours to division), the ability to withstand weak disinfectants, aerobics and intracellular pathogenesis. The bacterium is able to survive dormant in macrophages (scavenger cells of the immune system) and, after years of waking up, then to divide ( dormancy ). At the genomic level, an unusually large part of its genes encodes the enzymes for the production of lipolysis (fat-splitting) and lipogenesis (fat synthesis) enzymes. The lipids in the cell wall mask underlying molecular structures that induce a suitable immune response in other bacteria. In addition, the bacterium is not only able to live on its own fat layer deposited in the cell wall, but also to collect and use external cholesterol that is found in humans during the infection.

Intracellular Pathogenesis

M. tuberculosis has developed several mechanisms in order to be able to survive in the phagosome : it initially has a waxy, fat-rich cell wall, which enables it to defend itself against its destruction within the immune system. The phagosome is unable to split open the outer layer of the pathogen's cell wall. In addition, the outer wax layer contains lipoarabinomannan (LAM), a glycolipid that, together with a phosphatase, disrupts the signal transduction of the phagosome so that it does not go through the full destruction program.

Furthermore, several enzymes ( catalase , superoxide dismutase and others) are excreted by the bacterium , which eliminate any danger from reactive oxygen and nitrogen species (the catalase also acts as peroxynitritase ). Finally, the bacterium brings itself into a hibernation-like state ( dormancy ), in which no DNA replication and cell division takes place, and the organism lives anaerobically on its own fat layer on the back burner. As a result, many antibiotics that otherwise interfere with normal cell processes become ineffective.

In addition, there is an increased mutation rate due to reading errors in the DNA polymerase and reactive oxygen species (ROS) generated by the macrophages , which damage the DNA of the bacterium and lead to mutations even in the case of latent infection . This means that the bacterium can develop resistance even if it does not divide.

Infection, disease, therapy in humans

The transmission usually takes place through a droplet infection . The main entry point is the lungs. Infection of the lungs leads to the formation of nodules and destruction of the lung tissue, as well as the spread of tuberculous foci in the body. Malnourished and debilitated people are particularly susceptible to the disease. Today about every third person in the world is infected with Mycobacterium tuberculosis. In third world countries in particular, antibiotic treatment is difficult because it takes months. In addition, there are more and more cases in which the pathogen is resistant to many antibiotics. Tuberculosis kills 2 million people every year and, along with AIDS and malaria, it is the most widespread infectious disease in the world.

Infection and disease in farm animals and domestic animals

Animals are always infected by people suffering from overt tuberculosis. As a result, cattle are not only affected by the M. bovis variant ; In Ethiopia, for example, M. tuberculosis was found in up to a quarter of free-range animals , while fenced animals were partially infected with M. bovis . The cause is probably the habit of the shepherds there to spit chewed tobacco into the mouth of cattle to fight parasites.

A disease was also observed in pigs , horses , sheep and goats . Chickens are largely resistant to M. tuberculosis . Diseased animals usually only develop a local process that heals quickly. In such cases, it is advisable to check the caregivers for tuberculosis.

The infection of domestic animals that live in close household with humans is much more serious. Dogs , cats and possibly parrots are first infected by openly tuberculous people, develop mostly open tuberculosis themselves and thus form a dangerous source of infection for people who come into contact with them.

Antibiotic resistance

Due to several properties, M. tuberculosis is able to render antibiotics harmless. In particular, the impermeability of the outer waxy cell wall means that foreign substances are only absorbed via transport proteins, which can be very selective. Furthermore, several of the functioning antibiotics are dependent on activation by bacterial enzymes ( prodrug ). Many others are effectively removed from the cell by efflux pumps . Finally, the antibiotics' targets are all enzymes or ribosomes. Since proteins are involved in all of these processes, a mutation at the corresponding position in the protein is often sufficient either to eliminate a point of attack, to deactivate activating enzymes, to overexpress inhibited enzymes and efflux pumps, or to specialize in importing an antibiotic to its effect the bacterium loses and resistance develops. The following is a table of the known antibiotics for M. tuberculosis with their mechanisms of action and resistance:

antibiotic Site of action Resistance
gene (s)
Mechanism of Resistance
Isoniazid , ethionamide (Prodrug) fatty acid synthesis katG, ahpC, ndh Loss of activation
content Mutation at the point of attack
Rifampicin Elongation of mRNA transcription rpoB Mutation at the point of attack
Pyrazinamide (Prodrug) trans-translation pncA Loss of activation
Streptomycin Initiation of translation rpsL Mutation at the point of attack
Ethambutol Arabinogalactan Biosynthesis embB,? Mutation at the point of attack
Fluoroquinolones DNA replication gyrA, gyrB Mutation at the point of attack
? Efflux pumps
MfpA ?
Kanamycin Translation rrs Loss of ribose methylation
ice cream Breakdown of the antibiotic
4-aminosalicylic acid (Prodrug)? thyA? ?
Macrolides Translation erm37 Ribosome methylation
Linezolid , PNU100480 Initiation of translation (23S rRNA) Mutation at the point of attack
D-cycloserine Peptidoglycan synthesis alr Mutation at the point of attack
TMC207 ATP synthesis atpE,? Mutation at the point of attack
PA-824 , OPC-67683 (Prodrug) lipid synthesis? Rv3547 Loss of activation
MetSox Glutamate Synthesis glnA1, glnA3 Deletion of a base with the following overexpression
Halicin ( drug approval not yet granted .)


Common abbreviations:

MDR-TB : multi-resistant tuberculosis bacterium
XDR-TB : extremely resistant tuberculosis bacterium

M. tuberculosis strains that show at least one resistance to the TB standard antibiotics isoniazid and rifampicin are referred to as multi- resistant . The first major MDR-TB epidemic occurred in New York in the early 1990s and mainly affected people infected with HIV and medical personnel. In 2007 around 20 percent of all isolates worldwide were multi-resistant.

Those MDR-TB strains with additional resistance to at least one fluoroquinolone antibiotic and at least one of the drugs capreomycin , kanamycin or amikacin are called extremely resistant . One of the first XDR-TB outbreaks occurred in a rural hospital in KwaZulu-Natal in 2005 . The risk of such epidemics is not limited to Africa, as XDR-TB is now found on six continents and averaged around 10 percent of MDR-TB cases in 2007.

In the meantime, linezolid is also becoming more and more resistant.

The term TDR-TB ( totally drug resistant tuberculosis ), which inter alia. brought up for discussion in connection with tuberculosis cases in India is not recognized by the World Health Organization.


The gold standard for detection is cultivation in the laboratory on a selective culture medium such as Lowenstein-Jensen agar and microscopic detection using Ziehl-Neelsen staining . It is possible to accelerate growth in Middlebrook 7H10 Agar . Unconventional approaches are microcaloric detection of slow growth or the detection of very small amounts of typical volatile esters (methylphenyl acetate, methyl p-anisate, methyl nicotinate) by honey bees .

The analysis of heat-sterilized material by means of mass spectrometry could develop as the new gold standard . Due to the different lipid profile, among other things, it is possible to differentiate between individual Mycobacterium species in a short time and with a high degree of certainty .


The French doctor Jean-Antoine Villemin (1827-1892) showed as early as 1865 that tuberculosis can be transmitted. However, it was still mostly mistaken for a constitutional disease. The bacterium was discovered by Robert Koch in 1882 and isolated for the first time, with which Koch had definitively proven transmission by a living microorganism. Through pure culture and animal experiments, he was able to prove in the form of Koch's postulates that tuberculosis is caused by M. tuberculosis .

Mycobacterium tuberculosis is traced back to a 40,000 year old predecessor to which Mycobacterium leprae and Mycobacterium bovis are also traced back.

In 2019, a potentially effective antibiotic against Mycobacterium tuberculosis was found with the molecule halicin .

Reporting requirement

In Germany, the direct detection of Mycobacterium tuberculosis must be reported by name in accordance with Section 7 of the Infection Protection Act . The reporting obligation only applies if the direct evidence indicates an acute infection and, subsequently, for the result of the resistance determination; in advance also for the detection of acid-fast rods in the sputum. The obligation to notify primarily concerns the management of laboratories ( § 8 IfSG).

In Switzerland, the positive and negative laboratory-analytical findings of pathogens from the Mycobacterium tuberculosis complex must be reported to laboratories in accordance with the Epidemics Act (EpG) in conjunction with the Epidemics Ordinance and Annex 3 of the Ordinance of the FDHA on the reporting of observations of communicable diseases in humans .


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Web links

Commons : Mycobacterium tuberculosis  - Collection of pictures, videos and audio files

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