Unravelling Tuberculosis: How Mycobacterium tuberculosis Evades the Immune System
- October 15, 2024
- Posted by: OptimizeIAS Team
- Category: DPN Topics
Unravelling Tuberculosis: How Mycobacterium tuberculosis Evades the Immune System
Sub :Sci
Sec :Health
Why in News
Researchers from CSIR-Centre for Cellular and Molecular Biology (CCMB), Hyderabad have made significant strides in understanding how Mycobacterium tuberculosis (Mtb), the bacteria responsible for tuberculosis (TB), evades the immune response. A recent study published in the journal eLife highlights key enzymes that help Mtb survive in hostile environments, providing potential targets for new drugs.
Tuberculosis in India:
TB is a major public health concern in India, one of the highest TB burden countries globally. The Indian government has made TB elimination a key healthcare goal, with enhanced focus on diagnostics, patient management, and tracking.
What is Tuberculosis: Tuberculosis (TB) is an infectious airborne bacterial disease caused by Mycobacterium tuberculosis.
TB commonly affects the lungs (pulmonary TB) but can also affect other parts (extrapulmonary TB)
Tuberculosis spreads from person to person through the air, when people who are infected with TB infection cough, sneeze or otherwise transmit respiratory fluids through the air.
Genome Size: Mtb’s genome consists of 4.4 million base pairs, far larger than other respiratory bacteria like Staphylococcus aureus (2.8 million) and Streptococcus pneumoniae (1.9-2.7 million). This extensive genome enables Mtb to produce a wide variety of proteins to evade immune defenses.
What is Multidrug-Resistant TB (MDR-TB):
- In MDR-TB, the bacteria that cause TB develop resistance to antimicrobial drugs used to cure the disease.
- MDR-TB does not respond to at least isoniazid and rifampicin, the 2 most powerful anti-TB drugs.
- Treatment options for MDR-TB are limited and expensive.
About Antimicrobial Resistance (AMR):
- Increasing antimicrobial resistance (AMR) in Mtb is undermining the effectiveness of existing treatments. Researchers are urgently working to develop new antibiotics that can combat resistant strains.
- Antimicrobial Resistance (AMR) is the ability of a microbe to resist the effects of medication previously used to treat them. It is also known as antibiotic resistance.
- As a result, the medicines become ineffective and infections persist in the body.
- The WHO defines antimicrobial resistance as a microorganism’s resistance to an antimicrobial drug that was once able to treat an infection by that microorganism.
- The resistance to antimicrobials is a natural biological phenomenon. However, the misuse and overuse of antibiotics accelerates the development of AMR.
- Microbial resistance to antibiotics has made it harder to treat infections such as pneumonia, tuberculosis (TB), blood poisoning (septicaemia) and several food-borne diseases.
Coevolution of Mtb and Humans
The Mtb pathogen has coexisted with humans for millennia. Evidence suggests that the Mtb complex has been present for over 70,000 years, giving the bacteria ample time to adapt to human biology.
Macrophage Invasion: Mtb primarily infects macrophages, the body’s first line of defense against invading pathogens. Macrophages usually destroy microbes through oxidative stress, but Mtb has evolved to survive and multiply inside them.
About Macrophage:
- Macrophages are a type of white blood cell (phagocyte) crucial for the innate immune response.
- Phagocytosis: They engulf and digest foreign particles, bacteria, and dead or damaged cells through phagocytosis.
- Found in nearly all tissues, they are especially abundant in areas like the lungs, liver (Kupffer cells), brain (microglia), and spleen.
- Derived from monocytes, a type of white blood cell, which transform into macrophages when they migrate from the blood into tissues.
- They initiate oxidative stress reactions involving peroxides and free radicals to destroy pathogens, including bacteria, viruses, and fungi.
- Macrophages present antigens to T-cells, helping trigger the adaptive immune response.
- TB Survival Mechanism: In tuberculosis, Mycobacterium tuberculosis can evade macrophage defense, surviving and multiplying within the cells by forming protective clusters.
- Macrophages can survive for weeks to months in tissues, continuing their protective and regulatory roles.
About Cysteine Synthase Enzymes:
- Researchers at CCMB identified that two enzymes, CysK2 and CysM, are crucial for Mtb’s survival during nutrient deficiency and oxidative stress. When these enzymes were disabled, Mtb’s ability to produce antioxidants was impaired, reducing its survival.
- Cysteine and Antioxidant Defense: One group of proteins of particular interest is cysteine synthase enzymes. These enzymes are responsible for synthesizing cysteine, a sulfur-containing amino acid crucial for producing antioxidants. Antioxidants disrupt oxidative stress, allowing Mtb to survive in macrophages.
- Cysteine is essential for producing antioxidants like glutathione, which help protect cells from oxidative stress.
- In Mycobacterium tuberculosis, cysteine synthases aid in surviving hostile environments by countering oxidative damage.
- Common types include CysK and CysM, which are involved in different pathways for cysteine biosynthesis.
- These enzymes are potential targets for antibiotics, as humans lack cysteine synthase, making bacterial inhibitors promising for TB treatment.