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Chemotherapeutic Agents

Chemical agents that are used to treat disease. Ideally the ones used to treat infectious disease destroy pathogenic microbes or inhibit their growth at concentrations low enough to avoid undesirable damage tot he host.



Microbial products of their derivatives that kill susceptible microbes or inhibit their growth.


Paul Ehrlich

German physician that began modern era of chemotherapy. He was fascinated with dyes that specifically bind to and stain microbial cells. He reasoned that one of the dyes could be a chemical that would selectively destroy pathogens without harming human cells.

By 1904, Ehrlich found that the dye trypan red was active against the trypanosome that causes African sleeping sickness and could be used therapeutically.

Subsequently Ehrlich and a young Japanese scientist named Sahachiro Hata tested a variety of arsenic-based chemicals oh syphilis infected rabbits and found that arsphenamine was active against the syphilis spirochete. Arsphenamine was made available in 1919 under the trade name Salvarsan and paved the way to the testing of hundreds of compounds for their selective toxicity and therapeutic potential.


Pencillin Discovery

The first true antibiotic. Initially discovered in 1896 by a 21 year old French medical student named Ernest Duchesne. His was work forgotten until Alexander Fleming accidentally rediscovered penicillin in September 1928.

After returning from a weekend vacation, Fleming noticed that Petri plate of Staphylococcus also had mold growing on it and there were no bacterial colonies surrounding it. It's suggested that a Panicillium notatum spore had contaminated the Petri dish before it had been inoculated with the staphylococci. The mold apparently grew before the bacteria and produced pencillin. The bacteria near the fungus were lysed. Fleming correctly deduced that the mold produced a diffusible substance, called pencillin.

Unfortunately, Fleming couldn't demonstrate that penicillin remained active in vivo long enough to destroy pathogens and thus dropped the research. But in 1939, Howard Florey (professor of pathology at Oxford University) read Fleming's paper on Penicillin. One of his workers, Ernst Chain, obtained the Penicillium culture from Fleming and set about purifying the antibiotic. Norman Heatley (biochemist) was enlisted to help. He devised the original assay, culture, and purification techniques needed to produce crude penicillin for further experimentation. When purified penicillin was injected into mice infected with streptococci or staphylococci, almost all the mice survived. Florey and Chain's success was reported in 1940, and subsequent human trials were equally successful.



Latin - vacca = cow (Edward Jenner)

A preparation of one or more microbial antigens used to induce protective immunity. Vaccination attempts to induce antibodies and activated T cells to protect a host from future infectin.



Result achieved by the successful delivery of vaccines.


Edward Jenner

Began the modern era of vaccines and immunization. He used cowpox as a vaccine against smallpox. He was a country doctor from England. He investigated the basis for widespread belief of the English peasants that anyone who had vaccina (cowpox) never contracted smallpox.

Jenner extracted the contents of a pustule from the arm of a cowpox-infected milkmaid, Sarah Nelmes, and injected it into the arm of 8 year old James Phipps. As Jenner expected, immunization witht he cowpox virus caused only mild symptoms in the boy. When he subsequently inoculated the boy with smallpox virus (considered an unethical act), the boy showed no symptoms of the disease. He had produced the very first vaccine.



A glyvopeptide antibiotic produced by Streptomyces orientalis. It's a cup-shaped molecule compsoed of a peptide linked to a disaccharide. The peptide portion blocks the transpeptidation reaction by binding specifically to the D-alanyl-D-peptidoglycan. The antibiotic is bactericidal for Staphylococcus and some members of the genera Clostridium, Bacillus, Streptococcus, and Enterococcus. It's given both orally and intravenously, and has been particularly important in the treatment of antibiotic-resistant staphylococcal and enterococcal infections.

However, vancomycin-resistant strains of Enterococcus have become widespread and cases of resistant Staphylococcus aureus have appeared. In this case, resistance is conferred when bacteria change the terminal D-alanine to either D-lactate or a D-serine residue. Vancomycin resistance poses a serious public health threat: vancomycin has been considered the "drug of last resort" in cases of antibiotic-resistant S. aureus.



Antibiotic produced by some species of Bacillus.


Inhibitors of Cell Wall Synthesis

The most selective antibiotics are those that interfere with bacterial cell wall synthesis. Drugs such as penicillins, cephalosporins, vancomycin, and bacitracin have a high therapeutic index because they target structures not found in eukaryotic cells.



Antibiotic. Most of them are derivatives of 6-aminopenicillanic acid and differ from one another WRT the side chain attached to the amino group.

The most crucial feature of the molecule is the B-lactam ring, which is essential for bioactivity. Many penicillin-resistant bacteria produce penicillinase, an enzyme that inactivates the antibiotic by hydrolyzing a bond in the B-lactam ring.

The structure of the penicillins resembles the terminal D-alanyl-D-alanine found on the peptide side chain of the peptidoglycan subunit. It's thought that this structural similarity blocks the enzyme catalyzing the transpeptidation reaction that forms the peptidoglycan cross-links. Thus formation of a complete cell wall is blocked, leading to osmotic lysis. This mechanism is consistent with the observation that penicillins act only on growing bacteria that are synthesizing new peptidoglycan.

However, the mechanism of penicillin action is actually more complex. Penicillins also bind to several periplasmic proteins and may also destroy the bacteria by activating their own autolytic enzymes. However, penicillin may kill bacteria even in the absence of autolysins or murein hydrolases. Lysis could occur after bacterial viability has already been lost. Penicillin may stimulate proteins called bacterial holins to form holes or lesions in the plasma membrane, leading directly to membrane leakage and death. Murein hydrolases also could move through the holes, disrupt the peptidoglycan, and lyse the cell.


Role of Antibiotics in Soil Microbes

They are used to eliminate competitors that are competing with them for their nutrients. Some microbes produce antibiotics to kill these bacteria as well.



Term coined to define all the genes of the host, including those of its microbiota; the microbiome reflects the combined or composite genetic background of a host and its microbiota. One goal of the Human Microbiome Project is to sort out the impact that microbial gene function has on human health and disease. In other words, since our 46 chromosomes don't appear to encode the products necessary for all biological functions of the human body, the project seeks to correlate the contribution of the microbial genes to human biological function.



in microbiology, is the ability of some bacteria to alter their shape or size in response to environmental conditions.


Eukaryotic Flagella Ultrastructure

Membrane-bound cylinder about 0.2 um in diameter. Located in the matrix of the organelle is the axoneme, which consists of nine pairs of microtubule doublets arranged in a circle around two central tubules. This is called the 9 + 2 pattern of microtubules. Each doublet has pairs of arms projecting from subtubule A (the complete microtubule) toward a neighboring doublet. A radial spoke extends for subtubule A toward the internal pair of microtubules with their central sheath. These microtubules similar to those in cytoplasm.

A basal body lies in the cytoplasm at base of flagellum. It's a short cylinder with nine microtubule triplets around its periphery (a 9 + 0 pattern) and is separated from the rest of the organelle by a basal plate. The basal body directs construction of these organelles. Flagella appear to grow through the addition of preformed microtubule subunits at their tips.


Lancefield Grouping System

A method by which streptococci can be placed in serologically distinguishable groups.

Serology is the scientific study of plasma serum and other bodily fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum.