How Sulfa Drugs Work !!!!!!!!!

Researchers have finally found out how sulfa drugs—the first class of antibiotics ever discovered—work at the molecular level. Sulfa drugs work by binding and inhibiting a specific enzyme called dihydropteroate synthase (DHPS). This enzyme is critical for the synthesis of folate, an essential nutrient. Mammals get folate from their diet, but bacteria must synthesize this vitamin. Sulfa antibiotics were first used in the 1930s, and they revolutionized medicine. After a few years, bacteria started to develop resistance to the drugs, and eventually penicillin replaced them as a first-line treatment. While antibiotic resistance remains a problem for this class of antibiotics, sulfa drugs are still commonly used to treat a variety of bacterial infections. 

Bacteria resistant to sulfa drugs often have mutations in the DHPS enzyme. These mutations occur on 2 floppy loops that sit near the enzyme's active site. Previous research had described most of the structure of DHPS, but the structure of the floppy, highly conserved loops remained elusive. Moreover, researchers didn't know how the chemical reaction occurs between DHPP and PABA. The scientists isolated the DHPS enzyme from 2 bacterial species: Bacillus anthracis, which causes anthrax, and Yersinia pestis, which causes plague. The scientists embedded DHPP and PABA in crystals of the enzyme. They then used X-ray crystallography to find high-resolution structures of these molecules at different stages of the chemical reaction.

The researchers found that the 2 floppy loops wrap around PABA early on and hold the molecule in place. The chemical reaction linking portions of PABA and DHPP takes place, and then the loops release the chemical reaction product. The structures also revealed the exact chemical reaction steps that occur between PABA and DHPP. Sulfa antibiotics work because they fit into the DHPS active site and take PABA's place. By embedding sulfa antibiotics into the enzyme crystals, the scientists found that the sulfa drugs are held in place by the floppy loop structures. However, a small portion of the drug sticks out of the binding pocket. The researchers discovered that DHPS mutations in drug-resistant bacteria occur near this small stuck-out portion.

Do creatine supplements improve muscular performance?

Creatine phosphate (CP) is a molecule stored in muscle that yields energy when the creatine splits from the attached phosphate. This energy is used to resynthesize the small amount of ATP (adenosine triphosphate) that is available to the muscle in the initial seconds of high intensity work (think 100-yard dash or a power lift). Because greater amounts of CP in the muscle can potentially allow for those high intensity efforts to be sustained a bit longer or to be performed more effectively, creatine supplementation has become popular within the last 15 years. Some research indicates that such supplementation can improve performance in the short term and in high intensity activities, but for more sustained activities it has little or no effect because of the ATP’s great dependence on aerobic metabolism. The long-term effect of such supplementation on the human body is unknown.

What are Killed (inactivated) vaccines?

When safe live vaccines are not available, either because attenuated strains have not been developed or else because reversion to wild type occurs too readily, it may be possible to use an inactivated preparation of the virulent organism to immunize the host. The organism is propagated in bulk, in vitro, and inactivated with either betapropiolactone or formaldehyde. These vaccines are not infectious and are therefore relatively safe. However, they are usually of lower immunogenicity and multiple doses may be needed to induce immunity. In addition, they are usually expensive to prepare. In subcellular fractions ,when protective immunity is known to be directed against only one or two proteins of an organism, it may be possible to use a purified preparation of these proteins as a vaccine. The organism is grown in bulk and inactivated, and then the protein of interest is purified and concentrated from the culture suspension. These vaccines are safe and fewer local reactions occur at the injection site. However, the same disadvantages of poor immunogenicity and the need for multiple boosters apply.

What is triclosan?

Triclosan has properties of a phenol and is extremely popular in antibacterial products such as hand sanitizers, antibacterial soaps, lotions, toothpastes, and even as an antimicrobial additive in plastics. Resistance to triclosan occurs in some bacterial species, and there is concern that resistance to triclosan may provide cross- resistance to antibiotics. This is of particular concern with antibiotic resistant strains of Staphylococcus aureus.