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Since Alexander Fleming discovered the antibiotic properties of the penicillin mold in 1929, two parallel processes have been unfolding. One is a marked drop in deaths due to infectious diseases. The other has been a dramatic demonstration of survival of the fittest. With increasing swiftness, disease-causing bacteria have become resistant to common antibiotics. Fears are growing that bacteria resistant to vancomycin, long considered the antibiotic of last resort, will soon emerge. These kinds of infections are usually found among seriously ill hospital patients, but even in the case of less serious infections, doctors are finding that even newer antibiotics are becoming less effective. Therefore, finding drugs that will work against resistant bacteria, or use novel mechanisms that make them less vulnerable to the development of resistance, are the primary focus of many researchers.

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.

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Note: The above information is intended to supplement, not substitute for, the expertise and judgment of your physician, pharmacist, or other healthcare professional. It is not intended to diagnose a health condition, but it can be used as a guide to help you decide if you should seek professional treatment or to help you learn more about your condition once it has been diagnosed.