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.

How many bacteria, I micron on each side, will fit in a typical human cell (about 25 microns on each side)?

Although it is not necessary to do so, we can make a simplifying assumption that both human cells and bacterial cells have the shape of cubes. Since the bacterial cells are I /25th the length of the human one, as many as 25 x 25 x 25 will fit inside. (Picture a large cube and start stuffing it with the little ones, 25 rows of 25 on the bottom layer, and 25 such layers); 25 x 25 x 25 =15,625. Since we are estimating, we should round off to about 16,000. We will later see that this consideration of bacterial cells fitting within human cells is not without significance, both in terms of mitochondria and chloroplasts and in terms of our immune systems.

How sex occurs in bacteria?

The occurrence of sex in bacteria was first described by Joshua Lederberg and Edward Tatum in 1946 (Nature, volume 158, page 558), who were studying mixed cultures of E. coli strains with various nutritional mutations. The mutant strains differed from the wild type strains in lacking the ability to synthesize growth factors such as amino acids and vitamins, similar to the strains in the present problem.
In one experiment, two triple mutants of E. coli, one requiring threonine, leucine, and thiamine, and the second requiring biotin, phenylalanine, and cystine were grown in mixed cultures. At very low frequency, recombinant strains with no growth-factor requirement were obtained. They ruled out spontaneous mutations and transformation by the culture medium as the source of recombinant strains. In the words of Lederberg and Tatum, "These experiments imply the occurrence of a sexual process in the bacterium Escherichia coli."