Israeli researchers discover method to fight superbugs

Robin Wulffson MD's picture
antibiotic resistance, superbugs, E. Coli, MRSA
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TEL AVIV, ISRAEL - Researchers at Sackler School of Medicine, Tel Aviv University reported that they have developed a new method of restoring antibiotic sensitivity to resistant bacteria. They published their findings in the January issue of the journal Applied and Environmental Microbiology.

They report that their process could eventually be used to fight hospital superbugs. In the United States, an estimated 70% of hospital-acquired infections are due to bacteria that are resistant to at least one antibiotic.

Using a process called lysogenization, scientists used bacteriophages to invade the cell wall of resistant bacteria and restore their sensitivity to antibiotics. Bacteriophages are viruses that can infect bacteria. They conducted their initial experiments with the bacteria Escherichia Coli and the antibiotics streptomycin and nalidixic acid. Genes from mutant or antibiotic-resistant E. coli were isolated in laboratory cultures and genetically engineered to reverse the resistance mechanism. The researchers then targeted the resistant genes using bacteriophages, which contianed the engineered genes. This process rendered the resistant E. coli significantly more sensitive to the antibiotics than control phages carrying mock genes.

The scientists noted that they believe that genetically engineered bacteriophages can be developed for any bacterium and used in hospital settings to reverse antibiotic resistance in bacteria that cause hospital-acquired infections.

Researchers said they expect genetically altered bacteriophages can be developed for any bacterium; these viruses then can be used in a hospital setting to reverse antibiotic resistance in bacteria that cause hospital-acquired infections. Once bacteria are lysogenized, they are less likely to infect humans and perpetuate the cycle of antibiotic-resistance.

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The researchers also conducted experiments with Tellurite, which is a substance that is toxic to bacteria. Supplementary treatment with Tellurite would kill bacteria missed by the bacteriophages.

One particularly virulent form of bacterium is methicillin-resistant Staphylococcus aureus (MRSA). Hopefully, a future study by the Israeli researchers will focus on this organism. S. aureus is an extremely versatile organism that can cause infections ranging from mild to severe in humans and animals. MRSA can cause a large number of serious illnesses that do not respond well to current medical treatment. It has evolved the ability to survive treatment with a number of antibiotics, including penicillin, methicillin, and cephalosporins. MRSA infections commonly occur in hospitals and other healthcare facilities, such as nursing homes.

Researchers around the globe are devoting a considerable to find treatments to combat MRSA and other hospital-acquired infections. For example, last August investigators at the David Geffen School of Medicine at UCLA and the University of Texas Medical Branch at Galveston announced that they had discovered a molecular process by which the body can defend against the effects of Clostridium difficile infection (CDI), pointing the way to a promising new approach for treating an intestinal disease that has become more common, more severe and harder to cure in recent years. Each year, several million people in the U.S. are infected with CDI, about double the incidence of a decade ago, mainly due to the emergence of a new, highly virulent strain of the bacteria that causes CDI. As a result of the study findings, the researchers are preparing to launch clinical trials using their discovery as a new CDI therapeutic approach.

CDI is a bacterial infection that can cause diarrhea and more serious intestinal conditions, such as colitis (inflammation of the colon). In the most severe cases, CDI can be fatal. It is most commonly acquired in hospitals by patients, particularly the elderly, who are being treated with antibiotics for another infection. Currently, one of two potent antibiotics is used to treat the infection; however, up to 20% of patients experience a relapse and a return of symptoms within a few weeks. C. difficile causes diarrhea and colitis by releasing two potent toxins into the gut lumen that bind to intestinal epithelial cells, initiating an inflammatory response. These toxins are released only when the bacteria are multiplying. When antibiotics are used to treat another infection, it changes the bacterial landscape in the intestines and, in the process, may kill bacteria that under normal conditions would compete with C. difficile for energy. Scientists believe this may be what provides the opportunity for the bacteria to grow and release their toxins.

The researchers found in laboratory studies that upon infection with C. difficile, human cells in the intestine are capable of releasing molecules that will neutralize these toxins, rendering them harmless. In animal studies, the researchers showed that using a drug to induce this process, known as protein s-nitrosylation, inhibited the toxins from destroying intestinal cells. This new approach might also be applied to the treatment of other bacterial infections. Forthcoming clinical trials will test this approach in humans. Caveat: Bacteriophages have yet to be tested on hospital superbugs such as methicillin-resistant Staphylococcus aureus (MRSA).

Reference: Applied and Environmental Microbiology

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