Wednesday, 10 December, 2003
'Super Bugs': The Rise of Antibiotic Resistant Bacteria - KHORRAM COUNTRY - THE COMMENTARY
By Babak Khorram
For humans, antibiotics are life-saving drugs. The discovery of penicillin in 1928 by Alexander Fleming ushered in a new era in treating infections. Over the past century, life expectancies throughout the world have soared. Much of this has been attributed to the usage of antibiotics to fight microbial infections. For bacteria, antibiotics are powerful agents of selection. During the past few decades, increased and uncontrolled usage of antibiotics has lead to resistant strains of bacteria.
There is strong scientific evidence that suggests that bacteria may mutate to resistant forms. In the presence of antibiotics, these resistant forms gain a selective advantage over the non-mutated susceptible forms. One such piece of evidence came from a study preformed by William Bishai and his colleagues. The study monitored an AIDS patient with tuberculosis from Baltimore, Maryland. Upon diagnosing the patient with tuberculosis, the researchers obtained cells of Mycobacterium tuberculosis (the pathogenic agent that causes tuberculosis) from his lungs. The cells were treated with several antibiotics including rifampin, an antibiotic commonly used in treating patients with tuberculosis. They found that all isolates were susceptible to rifampin and the other antibiotics were tested using the culture method. The patient was treated with rifampin and responded well. Two months after he was cured, however, the patient relapsed and died.
Once again, researchers obtained cells of M. tuberculosis from his lungs and cultured them. The cells were then treated with the same antibiotics as before including rifampin. The re-cultured cells were found to be susceptible to most of the antibiotics tested but not rifampin. As a result, the researchers sequenced the gene that is commonly associated with rifampin resistant M. tuberculosis cells. Bishai et al. found a mutation in the gene conferring rifampin resistance. Naturally, Bishai and his colleagues asked, did the resistant strain evolve in the patient or did the patient acquire it sometime after treatment?
In order to determine the answer to their question the researchers performed a genetic fingerprint of the first and second isolates (set of cells). Besides the mutation at the single gene the two isolates were exactly similar. To strengthen the evidence, Bishai and his colleagues obtained genetic fingerprints from 101 isolates of M. tuberculosis that were prominent in the Baltimore area in preceding years. They found that only two out of 101 isolates had matching genetic fingerprints with their rifampin resistant isolates. However, both of these isolates were susceptible to rifampin. Bishai et al. concluded that M. tuberculosis strain must have evolved within the patient due to strong selective pressure placed on the bacteria by rifampin.
Studies, such as the one performed by Bishai and his colleagues, have alarmed many scientists and health care professionals, who have called for reduced and controlled antibiotic usage. Indeed, over the past decade, antibiotics have been prescribed and used much more prudently. As a result, studies by many researchers have shown that drug-resistant pathogens have declined as antibiotic usage has declined. Thus, in the view of many scientists and health care professional, to combat these 'Super Bugs' we must reduce and control the usage of antibiotics.
This theory, however, assumes that there is always a cost for antibiotic resistance. For example, if antibiotic resistance is attained by a loss-of-function mutation then, in the absence of antibiotics, the loss-of-function is selected against. On the other hand, if antibiotic resistance is attained by a gain-of-function mutation then, in the absence of antibiotics, the expense of maintaining new functions may be selected against. In spite of this, one breakthrough study has shown that the long-term costs of antibiotic resistance can be eliminated by natural selection. The study, performed by Stephanie Schrag and her colleagues, showed that the cost of antibiotic resistance in E. coli cells could be offset by mutations elsewhere in the E. coli genome. Schrag et al. hypothesized that the cost of resistance need not persist and that compensatory mutations could make resistant strains as equally fit as sensitive strains.
The results reported by Schrag et al. are extremely alarming. If analogous studies report similar findings, then the effectiveness of antibiotics cannot be restored by simply withdrawing their use. The researchers, however, are careful to make a point that their results should in no way advocate against reduced or controlled use of antibiotics. Schrag et al. state that as long as the sensitive strains have some competitive advantage over resistant strains then in the absence of antibiotic, the sensitive strain will increase in frequency.
Nevertheless, it appears that the best defence against these 'Super Bugs' is to prevent sensitive bacterial strains from developing resistance in the first place. Thus, clinicians can use and maintain an arsenal of antibiotics when a patient's life is at stake. A report written by Stuart Levy, a leading bacteriologist, suggests guidelines for limiting the spread of resistant bacterial strains. Levy's recommendations include proper hygienic procedures by patients and their clinicians, the prudent prescription of antibiotics, and the use of antibiotics that target the most minimal range of bacterial species. These 'Super Bugs' have the potential to be the scourge of the future. If humans cannot limit the spread of antibiotic resistant bacteria, then we might be as helpless as we were a century ago.
You may reach Babak Khorram at bkhorram@thecommentary.ca
Mr. Khorram will return in the new year.