The development and widespread use of antibiotics must rank as the most remarkable of all medical advances made in the 20th century. Overconfident assertions that infectious diseases would soon be a thing of the past, however, now have a hollow ring to them. Viruses have proved to be more difficult to deal with than bacteria, and many viral diseases continue to elude effective treatment. Most alarmingly, the threat of resistant strains casts a shadow over all the past achievements of antibiotics. The major aim of scientists now must be to develop new antibiotics or other therapeutic strategies at a pace greater than that at which bacteria are developing resistance. In 2000, the FDA approved a new synthetic agent shown to be effective against both MRSA and vancomycin-resistant Enterococcus faecalis. Linezolid (Zyvox), which works by blocking the initiation of protein synthesis, belongs to a new class of antibiotics called oxazolidinones. It is the first new anti-MRSA compound to be introduced for more than 40 years.
Another approach to countering resistant forms is to identify and target the mechanism by which they combat antibiotic therapy. A team at Rockefeller University in New York have identified two genes that enable resistant forms to rebuild their cell walls after antibiotic treatment. By targeting these genes, they hope to restore the potency of a cell wall inhibitor such as penicillin. Perhaps by the time you read this, other, less conventional approaches will have yielded promising results (see Boxes 14.7 and 14.8), but you can be just as sure that bacteria will have new tricks up their sleeves, and that the battle of Man versus microorganisms will continue well into the new millennium.
Box 14.7 Bugs against bugs?
Scientists are always on the lookout for new weapons in the fight against infectious diseases. The emergence of resistant strains of pathogens means that new solutions continually need to be found. One novel line of research is hoping to utilise the bactericidal powers of a defence system used by certain insects. A sap-sucking species has been found that produces substances that interfere with bacterial protein synthesis. Most of these would harm protein synthesis in humans too, but certain peptides appear to be more selective in their action, protecting mice from E. coli and Salmonella infections. It may seem an unlikely source for a life saver, but then, so was Penicillium!
Box 14.8 Bacteriophages: our secret weapon against infections?
If bacteriophages are viruses that infect bacterial cells, why aren't they used in the fight against bacteria that cause infectious diseases? The short answer is: in some places they are! In the years following their discovery, there was considerable enthusiasm in some quarters for the notion that phages might be useful in the treatment of bacterial diseases. A particular attraction of phages as therapeutic agents is that they are extremely selective in their action, targeting one specific cell type. Early studies and trials had mixed results and before too long, antibiotics had revolutionised the treatment of infectious diseases in the West. This led to phage therapy being forgotten for several decades, but its use continued in the Soviet bloc countries, however, where even now phage preparations can be bought over the counter.
Western interest revived in the 1980s in the wake of the upsurge in antibiotic-resistant strains of bacteria, since when phages have attracted attention as possible allies in the control of infectious diseases, including some not responsive to antibiotic therapy. Several American companies have become involved in phage therapy, some in collaboration with the former Soviet state of Georgia, where research has been carried out over several decades.
Particular attention has been paid to veterinary applications, with a view to reducing the amount of antibiotic usage in animals, and it is hoped that one day phages may prove to be the weapon we need to fight antibiotic resistant strains such as MRSA and VRE.
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