Structural Biochemistry/MDR Pumps

Background Information


MDR stands for Multidrug‐ resistance, and describes large integral protein pumps located in the cell‐surface membranes of most living organisms. The main purpose they serve are to monitor chemicals passing through the cell membrane and eject ones that might endanger the well being of the cell. Normally they are beneficial to the cell's growth, but when growth is unwanted, i.e. in case of a bacterial infection or spreading cancer cells, MDR pumps become a problem. MDR pumps provide the ability to adapt and defend cells against some types of antibiotics. Cells employ the use of MDR pumps for protection against their environments, and researchers need to not only synthesize antibiotics that affect a targeted cell but they need to be able to cross the cell's defenses. The MDR pumps are activated by using packets of energy called ATP to force out unwanted toxins.

MDR pumps are found throughout the human body, including the brain, digestive tract, liver, and kidneys. These pumps carry out specific functions in the human body such as transporting molecules like hormones into and out of cells.

Researchers suggest that plants have evolved over time to produce chemicals that block MDR pumps, essentially having the same effect as what antibiotics need to have. This theory was tested by knocking out the MDR pump gene from a specific bacterial cell (Staphylococcus aureus). The bacteria was then exposed to the antibiotic berberine extracted from berberine berries. Berberine has proven to be typically ineffective in the presence of Staphylococcus aureus. However, it was extremely effective against the genetically modified bacteria without the MDR pump. The bacteria were also killed in the presence of the berberine when also exposed to a berberine extract that was believed to inhibit bacterial MDR pumps.

What is MDR Pumps?
MDR pumps are Multidrug‐ resistance pumps that are large proteins in cell‐surface membranes of microorganisms.They are used to monitor incoming chemicals and spit out ones that might endanger the bacteria.The gate must be opened for the pump to work.With the pump open, it can take up the drug.The pump's cytoplasmic gate closes, allowing the drug to be pumped out of the cell.

Bacteria and Drug Resistance
MDR pump can bestow deadly power-in the form resistance to antibiotics-to tiny organisms which is a bacteria. While bacteria MDR genes are not identical to those, the three-dimensional shape of all pumps is the same, they perform a similar task: preventing harmful molecules from setting up the cell's interior. Many MDR pumps confer resistance against first time used to treat pathogenic yeast and parasites. Resistance to drugs called antifungals that are used to treat yeast infections is increasing rapidly, affecting immunecrippled AIDS patient. MDR is saquinavir, a class of anti-AIDS frugs, called protease inhibitors. MDR pumps might also transport "normal" substances. In mammals, MDR pumps are positioned to encounter potentially harmful substances face to face in the intestine.

Fighting Cancer with MDR Pumps
Researchers are focusing on fighting cancer through the use of MDR pumps. Stem cells, which are those cells that have yet to be differentiated, have minimal MDR pumps in their membranes. Because of this, these stem cells are extremely sensitive to cancer-killing drugs. A specific major drawback to chemotherapy is bone marrow toxicity, which leaves the human body defenseless against deadly infections. Scientists and researchers devised a method to attach the defenseless stem cells with MDR pumps. In doing so, the stem cells can possibly stand a chance to the chemotherapy required to kill tumors in the human body.

MDR Pumps May Not Work During Pregnancy
Recent discovery by a pharmacologist Mary Vore of the University of Kentucky in Lexington shows that MDR pump will not work properly while the woman is pregnant. Basically, the MDR pump is malformed in pregnant women who have ICP, Intrahepatic Cholestasis of Pregnancy, which can endanger the growing fetus. The suggested reasons for this are the effect of estrogen and other pregnancy hormones during pregnancy.