OK, so here is my post on chemotherapeutic agents for microbe control. Some substances which inhibit microbial growth that occur in nature as part of another organisms defense mechanism we call antibiotics. Those which are purely synthetic compounds we call synthetic agents. The line between the two has blurred, since through our understanding of antibiotic chemical structure, we've been able to produce semi-synthetic antibiotics. Both differ from disinfectants and antiseptics in that they must kill bacteria within the body of the patient without causing undue damage to the patient.

Growth Factor analogs are substances structurally related to bacterial growth factors, but the difference is such that they cannot be used for the same function as the original growth factor. The first growth factor analog were the sulfa drugs, the simplest being sulfanilamide. Sulfanilamide is an analog to para-amino benzoic acid, which is part of folic acid, which is used as a nucleic acid precursor. Higher animals get their folic acid from external sources, bacteria generate their own, which is why sulfanilamide blocks bacterial growth but not higher animals. Trimethroprim also acts on folic acid metabolism.

Other synthetic compounds called quinolones block bacterial DNA gyrase from packaging bacterial DNA. Eukaryotes have chromosomes and use a different packing mechanism from prokaryotes. Some of the more famous quinolones are ciprofloxacin and norfloxacin. Quinolones work on all forms of bacteria, gram positive and gram negative, and are the drug of choice against anthrax and urinary tract infections.

Antibiotics that block protein synthesis by interacting with the bacterial ribosome include streptomycin, tetracycline, chloramphenicol, and cycloheximide. Tetracycline inhibits the protein elongation from the ribosome, while streptomycin inhibits the protein chain initiation. One of the issues with interfering with prokaryotic protein synthesis is that our own mitochondria use the same mechanisms and can be affected by high doses of the drugs in question.

Some antibiotics target RNA synthesis, such as streptovaricins and rifamycins by attacking the beta subunit of RNA polymerase. Actinomycin combines with DNA and prevents RNA synthesis.

Many antibiotics target the structures of the bacteria themselves, the most famous being penicillin like antibiotics called beta-lactams. Some beta-lactams like cephalosporins and penicillins target bacterial cell wall synthesis, notably the cross-linking of glycan linked peptide chains in the cell wall. Transpeptidases perform this linking, and the antibiotics bind to the transpeptidases, resulting in a weakened cell wall. This eventually leads to cell lysis. Vancomycin blocks the transpeptidase reaction by binding to the peptidoglycan precursor. These are generally very low toxicity, effective antibiotics, but some people do develop severe allergies to some of the compounds.

Streptomycin, neomycin, and others inhibit protein synthesis at the 30s subunit of the ribosome. These are known as the aminoglycoside antibiotics, but are not used as frequently anymore because of bacterial resistance and some large side-effects, such as toxicity to kidneys and balance problems.

Tetracyclines also inhibit protein synthesis at the 30s ribosomal unit. One of the values of the chemical structure of tetracycline is that there are 4 different substitution sites that allow for differing chemical analogs, some of which act in unknown ways but can actually cause bacterial cell lysis.

Erythromycin belongs to the family of antibiotics called macrolides. It inhibits protein synthesis at the 50s ribosomal subunit, and is very useful for people who have allergies to beta-lactam antibiotics like penicillin.

Polymyxins, imidazoles, polyenes and other antibiotics target the cytoplasmic membrane and alter it to make it leaky, diffusing the required cellular metabolic compounds. Polymyxins target bacterial cytoplasmic membranes and polyenes target fungal cell membranes.

The reason virii are so hard to treat compared to bacteria is that they use more of the animals existing replication, synthesis, and metabolic machinery instead of their own. This means fewer targets to disrupt, since disrupting those areas would mean you are disrupting the higher organisms own normal metabolic and catabolic processes.
- posted by Aargau @ 9:27 AM