posted
This is from an article that I came accross. It's probably old hat to some, but I'm sure that there are still a lot of people that might be helped by understanding it:
HOW DO BACTERIA BECOME RESISTANT? There are various ways in which bacteria evolve so that they can avoid the effects of an antibiotic. Some acquire genes that direct the assembly of enzymes that are capable of degrading antibiotics, or can chemically modify, and thus inactivate the drugs. In other cases, resistance genes cause bacteria to alter or replace molecules that the antibiotic normally binds to. Without these binding points, the antibiotic cannot perform its function. Bacteria may also do away with entry ports for a particular drug, and have even been capable of developing molecular pumps that expel the antibiotic from inside the cell before the medicines have had a chance to find their targets.
Bacteria resist antibiotics by developing mechanisms such as pumps, enzymes or resistant genes.
Armed with this knowledge, scientists are working on approaches that can revive the effectiveness of existing antibiotics. For example, many bacteria evade penicillin and its relatives by switching on an enzyme, penicillinase, which degrades those compounds. An antidote already exists that inhibits the action of penicillinase. This prevents the breakdown of penicillin and so frees the antibiotic to work normally. Scientists at Tufts University have developed a compound that jams the microbial pump that ejects tetracycline from bacteria; with the pump inactivated, tetracycline can penetrate bacterial cells effectively.
NEW APPROACHES TO ANTIBIOTIC RESISTANCE Responding to growing concerns about the looming danger of disease-causing bacteria that are impervious to the most potent antibiotics, researchers are using a variety of tactics to address the problem.
One is to use sophisticated microscopic techniques and computer software to understand the molecular structure of antibiotics and the enzymes and toxins bacteria use to invade cells and evade antibiotics. At the University of Pennsylvania Medical Center, for example, researchers used x-ray crystallography to solve the structure of vancomycin, which is presently considered the antibiotic of last resort to fight selected serious bacterial infections.
Researchers also seek out metabolic processes that are present in plants, fungi and bacteria, but are not found in vertebrates. In this way, they can develop compounds that inhibit enzymes in the process, or pathway, without causing side effects in humans.
They have found, for example, that particular disease-causing strains of enterococci produce large amounts of a substance called cytolysin. A bacterial toxin, cytolysin breaks down cell membranes, enabling the bacteria to invade other bacterial and mammalian cells. For decades, researchers have been studying how cytolysin is manufactured. They have found several points in the process where it may be possible to inhibit the enzymes involved. A drug that inhibits the activation of cytolysin could prevent the bacteria from multiplying without damaging other bacteria. This kind of compound would also not encourage the development of antibiotic resistance because it would not act directly on the organism.
Genomic research, or study of bacterial genes, is also helping researchers develop more targeted antibiotics. Rather than screening known families of chemical compounds, they are studying bacterial genes, which contain the information that tells a microbe how to cause disease. For example, researchers may be able to prevent Psuedomonas aeruginosa from colonizing the lungs by finding a drug that works against the gene that allows Pseudomonas to attach itself to the lung surface.
Dr. Carl Wieland, an Australian medical doctor, tackled the issue of antibiotic resistance in bacteria head-on. His article is worth quoting at some length.
This misconception [about antibiotic resistance and evolution] may be partly due to the fact that even many science graduates believe that the mechanism of antibiotic resistance involves the acquisition of new DNA information by accidental mutations... But resistance does not normally arise like this. Loss of control over an enzyme's production can engender antibiotic resistance. Take for instance penicillin resistance in Staphylococcus bacteria. This requires the bacterium to have DNA information coding for production of a complicated enzyme (penicillinase) which specifically destroys penicillin. It is extremely unlikely that such complex information could arise in a single mutation step, and in fact it does not. Mutation can cause the loss of control of its production, so much greater amounts are produced, and a bacterium producing large quantitites of penicillinase will survive when placed in a solution containing penicillin, whereas those producing lesser amounts will not. The information for producing this complicated chemical was, however, already present. (Carl Wieland, "Antibiotic Resistance in Bacteria," Creation Ex Nihilo Technical Journal, 8:1 (1994), p. 5.)
More examples:
A mutational loss or defect can cause resistance. For instance, Mycobacterium tuberculosis, the cause of TB, has an enzyme which (as well as its other useful functions) changes the antibiotic isoniazid into a form which destroys the bacterium. A mutation causes the loss of that enzyme and helps the pathogen withstand isoniazid. To give another example: the 4-quinolone antibiotics attack the enzyme DNA gyrase inside various bacteria. An informationally insignificant mutation which results in the substitution of one amino acid by another destroys the enzyme/antibiotic interaction. (Ibid.)
In other words, a number of these cases result from a mutation in the shape of an enzyme. Recall from your high-school biology class that enzymes have a specific shape that allows them to "lock" onto other molecules - or vice-versa. A simple change in shape can throw off a toxin that is trying to latch onto the enzyme, while the functional binding site of the enzyme (on another part of the enzymes' surface) may be unaffected.
Wieland continues:
More commonly, resistance arises through mutational defects that cause the inactivation of genes which control transport through the cell membrane. If the antibiotic is less efficiently taken up, it does not accumulate as readily to toxic levels. Antibiotic resistance commonly arises in ways that have nothing to do with mutation. For instance, in some microbes the antibacterial chemical, sulphonamide, works by blocking the ability to synthesize the vitamin folic acid. If the bacterium acquires new DNA which bypasses the block to produce this vitamin, then sulphonamide will not work as well. This pathogen is therefore resistant. (Ibid.)
Wieland goes on to explain the discovery of plasmid DNA, rings of DNA that can almost literally be tossed from one cell to another like a frisbee, sharing the information they contain without actually needing to reproduce. I direct the reader to any recent text on cell biology for further information. (For example, Lewis Kleinsmith and Valerie Kish, Principles of Cell and Molecular Biology (New York: HarperCollins College Publishers, 1995), pp. 100-104.)
-------------------- You're only a failure when you stop trying. Posts: 945 | From U.S | Registered: Oct 2004
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Marnie
Frequent Contributor (5K+ posts)
Member # 773
posted
Mutations...permanent or temporary?
I believe bacterial pathogens can alter their protein coats (cell walls) depending on the presence/absence of various nutrients that they want/don't want.
Or...in the case of Bb...it can roll up into a ball (cyst) and the resultant multilayers of the cell walls is very protective.
Bowen lab, I remember, seldom sees anything but a cell wall deficient form. This makes our antibodies, even IF healthy, ineffective.
We have to approach this from another angle.
Look at what is being depleted...what the pathogen wants from us.
We need the those nutrients too..to fight!
We normally fight off a lot of pathogens every day and our own bodies fight precancerous cells too...at a rate of about 4 a day.
P.S. Vancoymcin...that hits a sore spot with me. It put my dad (post op infection) in toxic hepatitis and destroyed his one good remaining kidney. We can't become THAT acidic.
We are most acidic at death.
We are supposed to be slightly alkaline to be healthy.
Posts: 9424 | From Sunshine State | Registered: Mar 2001
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posted
Borrelia has efflux pumps, cyst, CWD forms and continuosly upgrades itself via gene swapping. There's a reason why they call it the evil genius.
Posts: 731 | From Humble,TX | Registered: Feb 2005
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