It was a lovely october afternoon-the sun was shining and Sam was having a great

Question

It was a lovely october afternoon-the sun was shining and Sam was having a great time at the dog park with his dog, Scout. As the day came to a close, Sam was packing up Scout's toys when another dog tried to steal Scout's favorite chew toy. Without a second thought, Sam reached for the toy; unfortunately, the dog at Sam and bit him on the forearm. It was a quick bite-it didn't bleed very much and didn't seem very deep. Sam washed the bite with soap and water when he got home and didn't give it another thought. The next morning, noticed that the area was a little red and tende As the day went on, the soreness and redness Sam hurting. By the next morning, increased and Sam noticed that the area around the bite was also there was a pus-filled abscess present and his entire forearm was sore to the touch. Sam decides that he should go to the doctor ASAP. At the doctor's offce,the doctor drains the abscess and takes a sample for culturing. She then performs a gram-stain and the bacteria on the slide turns purple.

Explanation / Answer

C. Bedaquiline works by blocking an enzyme inside the Mycobacterium tuberculosis bacteria called ATP synthase. This enzyme is used by the bacteria to generate energy. Without the ability to generate energy, the TB bacteria die and the patient’s condition can start to improve.

ATP synthase complex, the site of ATP production, is located in inner membrane of mycobacterial mitochondria. It is composed of two structural domains; membrane embedded F0 domain and cytoplasmic located F1 domain with three subunits (a, b2 & c10–15) and five subunits (3, 3, , & ) respectively. The F0 domain with 10–15 ‘c’ subunits are arranged in the form of discs and the subunit of F1 domain has catalytic activity which combines one ADP with Pi to form ATP. Proton motive force generated across mitochondrial membrane by electron transfer chain, fuels the rotation of discs and results in activation of catalytic subunit of F1 domain resulting in ATP generation.

Protonated form of bedaquiline has high affinity for the ATP synthase complex. It specifically binds with a distinct position at the interface of ‘a’ and ‘c’ subunit in F0 domain and blocks rotation of discs and thereby the entire process of ATP synthesis. In vitro studies also proved that binding affinity of bedaquiline is not influenced by excess proton, pH or other electrostatic interactions. Human ATP synthase complex have similar domain configuration with very narrow protein sequence similarity.This information can assure that bedaquiline might be a safe drug in terms of pharmacodynamic aspects.

ATP yield normal- 38 molecules

ATP yield in the presence of antibiotic- 0 molecules.

D. Bacteria utilize carbon as a source of energy.This is the easy source of energy as it is present in ample amounts providing sufficient amounts of energy by their metabolism.

E. Switch from aerobic to anaerobic metabolism causes energy requirement to decrease.As in aerobic metabolism energy yield is very high when compared to anaerobic mode.Under anaerobic conditions, the rate of glucose metabolism is faster, but the amount of ATP produced is smaller. When exposed to aerobic conditions, the ATP and Citrate production increases and the rate of glycolysis slows, because the ATP and citrate produced act as allosteric inhibitors for phosphofructokinase 1, the third enzyme in the glycolysis pathway. So, from the standpoint of ATP production, it is advantageous for an organism to utilize the Krebs Cycle in the presence of oxygen, as more ATP is produced from less glucose.

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