Mycobacterium tuberculosis

Mycobacterium tuberculosis, also known as Koch's bacillus, is a type of pathogenic bacteria that causes a disease called tuberculosis. It was first discovered in 1882 by Robert Koch. This kind of bacteria has a waxy coating, mostly because of something called mycolic acid. This waxy coating makes it hard to see under a microscope, so scientists use special stains like Ziehl–Neelsen or fluorescent stains such as auramine to spot it.

Mycobacterium tuberculosis needs a lot of oxygen to grow and it usually infects the respiratory system, especially the lungs. There are a few main ways doctors check for tuberculosis, including the tuberculin skin test, looking at samples with an acid-fast stain, growing the bacteria in a lab through culture, and using a test called polymerase chain reaction.

In 1998, scientists were able to read the full genome of M. tuberculosis, which helped them learn more about how this bacterium works and how to fight it.

Microbiology

Mycobacterium tuberculosis requires oxygen to grow and cannot move on its own. It grows very slowly, dividing only once every 18 to 24 hours. This is slower than most other bacteria. The bacteria have a small rod shape and can survive in dry conditions for weeks because of its special outer layer, which contains fats like mycolic acid.

Usually, scientists use a special dye to see bacteria under a microscope, but M. tuberculosis does not take up this dye because of its mycolic acid. Instead, they use different colored stains to see it. The bacteria often appear in groups that look like strands of rope because of the fats in their outer layer. In tissues, M. tuberculosis can form clusters that look like small bumps.

Growing M. tuberculosis in a lab takes a long time, as it doubles only about once a day. Scientists use different special liquids or gels to help it grow, and it can take several weeks to see visible colonies. Tests help confirm it is M. tuberculosis.

The bacteria are very small. They have tiny parts called ribosomes that help them make proteins.

M. tuberculosis is part of a group of related bacteria that includes several other species such as M. africanum, M. canettii, M. bovis, and others.

Pathophysiology

Humans are the only source of M. tuberculosis. The bacteria are not spread by shaking hands, touching surfaces, or sharing food or drinks. The main way it spreads is through tiny drops of air from a person who has the disease when they cough, sneeze, talk, or sing.

When these bacteria get into the lungs, they are taken in by special cells called macrophages. The bacteria have a special coating that helps them survive inside these cells. This coating stops the cells from breaking down the bacteria. The bacteria also have ways to hide from the body’s defenses, which helps them stay alive and multiply. Over time, this can lead to a group of immune cells forming around the bacteria.

Symptoms of the disease caused by M. tuberculosis include coughing for more than three weeks, pain in the chest when breathing or coughing, weight loss, tiredness, fever, sweating at night, chills, and loss of appetite. The bacteria can also spread to other parts of the body, causing problems like pain in the back or blood in the urine.

Strain variation

Scientists study different types of M. tuberculosis to understand how the disease spreads. They used to look at the bacteria using a method called pulsed field gel electrophoresis, but now they use a simpler method called variable numbers of tandem repeats (VNTR). This helps them tell different strains apart by looking at repeated pieces of DNA in the bacteria’s genes.

Genome

The genome of the H37Rv strain was found in 1998. It is very big, with 4 million pieces of DNA called base pairs and 3,959 genes. Scientists know what 40% of these genes do, and they have ideas about another 44%. The genome also has six special genes called pseudogenes.

The genome has many genes that help the bacteria use fats for energy, especially to make its waxy coating. This coating helps the bacteria survive inside its host. The bacteria can use cholesterol from the host as food.

About 10% of the genes are in special families called PE/PPE. These genes make proteins that help the bacteria grow inside host cells.

Scientists have found nine special types of RNA in the bacteria, and they think there might be 56 more.

Research in 2013 studied how some types of the bacteria can resist antibiotics. They found new genes that help the bacteria fight drugs. Recent studies show that these bacteria stay stable in their DNA but use other ways to survive antibiotics.

The bacteria also have special enzymes called DNA methyltransferases that change their DNA, which might help them survive better in different situations.

Evolution

The Mycobacterium tuberculosis complex (MTBC) first developed in Africa, most likely in the Horn of Africa. This group includes several types that infect animals, such as M. africanum, M. bovis, and others. These animal-related types are closely connected to M. tuberculosis.

Scientists have found that the main types of M. tuberculosis that infect humans can be grouped into seven lineages. These lineages help us understand how the bacteria spread around the world. Some lineages are found mainly in certain regions, while others have traveled far and wide. Studies suggest that M. tuberculosis may have evolved alongside humans, spreading out of Africa as human populations grew and moved.

One of the most widespread lineages, Lineage 4, likely originated in Europe and spread globally with European explorers, reaching the Americas after 1492. Evidence of tuberculosis has even been found in very old human remains from around 7000 BC in the Levant.

Antibiotic resistance (ABR)

See also: Antimicrobial resistance and the experimental antibiotic Ganfeborole

Mycobacterium tuberculosis is a type of bacteria that is hard to treat with antibiotics. This is a problem for health around the world. Some places, like China, India, Russia, and South Africa, have more of these hard-to-treat cases.

Multidrug-resistant tuberculosis (MDR-TB) means the bacteria do not respond to two main antibiotics, isoniazid and rifampin. This makes treatment harder. Scientists are looking for new ways to fight these bacteria.

Host genetics

Some people may be more likely to get sick from M. tuberculosis because of their genes. There are rare health problems that can make a person more likely to get infections from certain bacteria, including M. tuberculosis.

Studies show that genes can affect how likely someone is to get sick from M. tuberculosis. Recent research found a few specific places in our DNA that may increase the risk of getting this infection. These gene changes have a moderate effect on risk.

DNA repair

Mycobacterium tuberculosis lives inside host cells and faces many attacks that can damage its DNA. These attacks come from harmful substances made by the host to fight the infection.

The bacteria have special ways to fix this damage. One way involves a protein called DnaE2, which helps the bacteria survive during infection. M. tuberculosis can use two main methods to repair broken DNA strands. Even if one method does not work, the bacteria can still survive using the other method. This helps the bacteria continue to live inside the host.

History

Main article: History of tuberculosis

Mycobacterium tuberculosis, also called "Koch's bacillus", was first found in 1882 by Robert Koch, who later won a Nobel Prize for this work in 1905. People have had this disease for a very long time, but it was described in more detail in 1720 by a doctor named Benjamin Marten. He thought it might be spread by tiny living things in the air.

The number of people getting this disease has gone down over the years, but there was a small increase during the Covid-19 pandemic.

Vaccine

The BCG vaccine helps protect children from serious tuberculosis sickness. It works best where tuberculosis is common, but it does not always stop the most common type in adults. That is why it is not usually given in places where tuberculosis is rare, like the United States.

The BCG vaccine can also help make the body’s first defense against infections stronger for a long time. Some studies suggest it might also help the body respond better to other illnesses, like COVID-19.

There are also special vaccines made from DNA that could be used with the BCG vaccine. These might help make treatment for tuberculosis shorter in the future.