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 special kind of bacteria has a waxy coating on its surface, mostly because of something called mycolic acid. This waxy coating makes it hard to see under a microscope using regular methods, 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 takes a very long time to grow, dividing only once every 18 to 24 hours, which is much slower than most other bacteria. This bacteria has 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 with special cells inside them.

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 like looking for certain proteins or using genetic tools help confirm it is M. tuberculosis.

The bacteria are very small, measuring about 2.71 micrometers long and 0.345 micrometers wide. They have a certain number of 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 known source of M. tuberculosis. The bacteria are not spread by shaking hands, touching surfaces, or sharing food or drinks. Instead, 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. However, 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, which can help control the infection but sometimes also help it spread.

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 if the spine is affected or blood in the urine if the kidneys are affected.

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 published in 1998. It is very big, with 4 million pieces of DNA called base pairs and 3,959 genes. Scientists have figured out what 40% of these genes do, and they have ideas about what another 44% might do. The genome also includes six special genes called pseudogenes.

The genome has many genes that help the bacteria use fats for energy, especially for making its waxy coating. This waxy coating is very important for the bacteria to survive inside its host. The bacteria can even use cholesterol from the host as a food source.

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

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

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

The bacteria also have special enzymes called DNA methyltransferases that change their DNA in certain ways, 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. Besides M. tuberculosis, 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 and are considered part of the same group.

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. However, newer research using ancient DNA suggests that the bacteria may have appeared more recently than previously thought, perhaps only 4,000 to 6,000 years ago.

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 does not share its DNA with other bacteria in a certain way. Even though it changes slowly, it is becoming harder to treat with antibiotics, which is a big problem for health around the world. In 2019, about 3.4% of new cases and 18% of cases that had been treated before were resistant to antibiotics. Some places, like China, India, Russia, and South Africa, have more of these resistant cases.

Multidrug-resistant tuberculosis (MDR-TB) means the bacteria do not respond to at least two main antibiotics, isoniazid and rifampin. This makes treatment harder. The bacteria have special parts on their surface that help them stay protected, making it tough for antibiotics to work. Scientists are looking for new ways to fight these tough bacteria, including targeting important parts of their cell walls and studying how they move materials in and out of their cells.

Host genetics

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

Studies have shown that genes can affect how likely someone is to get sick from M. tuberculosis. Recent research looking at many genes at once 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. These substances can change and break the DNA in different ways.

The bacteria have special ways to fix this damage. One way involves a protein called DnaE2, which helps the bacteria survive during infection, even though it is not very accurate. 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 comes from a related bacteria and helps protect children from serious tuberculosis sickness. It works best in places where tuberculosis is common, but it does not always stop the most common type of the disease in adults. Because of this, it is not usually given in the United States where the risk of getting tuberculosis is low.

The BCG vaccine can also help make the body’s first line of defense against infections stronger for a long time. This is different from the body’s usual way of fighting off sickness, and it can involve changes in certain cells. Some studies suggest that having the BCG vaccine might also help the body respond better to other illnesses, like COVID-19.

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