A new technique would help combat drug-resistant infections
drug-resistant bacteria have been posing serious threats to human life for long. Now, researchers have developed a genetic engineering technique that helps render such bacteria drug sensitive. A team of researchers led by Sidney Altman at the Yale University, New Haven, Connecticut, usa , used plasmids to infiltrate drug resistant strains of Escherichia coli . Plasmids contain synthetic genes coding for small oligonucleotides called external guide sequences (esgs). The method helped the researchers to render drug-resistant cultures of e coli susceptible to commonly used antibiotics (Proceedings of National Academy of Sciences , Vol 94, No 16).
Scientists have been attempting to disable antibiotics resistance of the bacterial genes, using a method called antisense. The technique involves designing a genetic sequence that binds messenger rna (mrna ). The messenger serves as an intermediate between dna and protein during protein synthesis for the resistant gene. With the help of this method, the bacterial gene cannot be read by the bacterium's protein synthesis machinery and hence cannot grow.
But Altman and his colleagues have used a more efficient method using one of the bacterium's own enzymes for destroying the m rna . The enzyme employed rna se-p is involved in processing the bacterium's transfer rna (trna) that helps m rna to produce proteins. rna se- p cuts the double stranded t rna into single strand opposite the genetic sequence Adenine Cytocine Cytocine Adenine (acca).
They produced antisense strands of rna to bind these sections of m rna that are involved in drug resistance of the bacteria. These antisense strands carrying an acca sequence on one end suspend free and flag down the rna ase-p, fooling the bacterial enzyme that m rna is the target it wants to cleave.
These esgs were packed into plasmids, loops of genetic material that are passed from generation to generation by the bacteria. Altman's group tested these against laboratory cultures of e coli resistant to antibiotics ampicillin and chloramphenicol. They found that the plasmids with the esgs quickly made the entire culture susceptible to antibiotics. Researchers associated with microbial resistance are upbeat with the invention and feel that this could be a novel method of getting back at the increasingly combative bacteria.
Further studies are being conducted to know whether the technology works in patients suffering from drug-resistant infections. A New York-based biotechnology firm, Innovir has already taken up a project in this regard. As the esgs could be broken down in blood stream, the researchers expect that the new technology may work well with infections such as those on skin, lungs or intestinal infections.
The method may help produce a drug that could stop some of the most persistent infections such as antibiotic-resistant Staphylococcus. The bacterium leads to deadly wound infections. Recently, the Centres for Disease Control and Prevention, Atlanta, usa, sounded alarm about the infection when even the most potent antibiotic vancomycin could not combat the Staph bacteria. Vancomycin is considered the last in line of drugs to control such fatal infections.
Many pharmaceutical companies are now gearing up to meet the challenges posed by drug-resistant bacteria. An estimated us $200 million for research and development and about 10 years are required for a drug to come into market. In such circumstances, if the method devised by Altman's team becomes widely applicable, it would be a cheaper alternative of combating drug-resistant strains than the current widely followed approach of discovering new drugs.
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