MIT Researchers Develop New Strategies To Fight Drug-Resistant Bacteria
By C. Rajan, contributing writer
Engineers at MIT have developed two different technologies that could help combat drug-resistant bacteria.
Drug-resistant bacteria, also called superbugs, have become one of the major health problems globally, infecting more than 2 million people in the U.S. alone, and causing over 23,000 deaths annually. Even with the recent interest in antibiotics development in the pharmaceutical industry and incentives from the government, few new classes of antibiotics have been discovered that can kill these superbugs.
Dr. Timothy Lu, associate professor of biological engineering, electrical engineering and computer science at MIT, and his team have developed two new technologies, a gene-editing system and high-speed genetic screens, which will both hopefully lead to new drugs to help fight the growing crisis posed by drug-resistant bacteria.
- Gene-editing system
Dr. Lu and his colleagues have developed a novel gene-editing system which allows them to disable any target gene. This tool can help to selectively kill bacteria that are carrying harmful genes responsible for disease or antibiotic resistance.
The researchers targeted specific genes that allow bacteria to survive antibiotic treatment. Then, they used the CRISPR genome-editing system to target those genes and modify them.
The CRISPR system involves a set of proteins which constitute the defense system of bacteria, including a DNA-cutting enzyme called Cas9, which binds to RNA guide strands that target specific sequences.
To use this tool against bacteria, Dr. Lu and his team designed their RNA guide strands to target genes for antibiotic resistance. They went after two genes: NDM-1, which allows bacteria to resist a broad range of beta-lactam antibiotics, including carbapenems, and another antibiotic resistance gene encoding SHV-18, a mutation in the bacterial chromosome providing resistance to quinolone antibiotics.
When the researchers turned the CRISPR system against these two genes, they were able to effectively kill the bacteria carrying these genes. The CRISPR system could also be used to selectively remove specific bacteria from diverse bacterial communities based on their genetic signatures.
The researchers are now testing this approach in mice, and they anticipate that this strategy could eventually be adapted to deliver the CRISPR components to treat infections or remove other unwanted bacteria in patients.
The study has been published this month in Nature Biotechnology.
(b) High-speed genetic screening
The researchers also developed another tool for fighting antibiotic resistance. This technology called CombiGEM rapidly screens for genetic combinations that sensitize bacteria to different antibiotics.
Using this technology, they identified the specific gene combinations that enhanced the killing of target bacteria by 10,000- to 1,000,000-fold, for each antibiotic. The researchers are now trying to work out how these genes help the bacteria fight antibiotics.
With a better understanding of how these genes influence antibiotic resistance, the researchers could now try to design new drugs that mimic the effects, Dr. Lu says. In fact, if scientists are able to find a safe and effective delivery method, the genes themselves could also be used as a possible treatment, Dr. Lu says.
This study was reported last month in the Proceedings of the National Academy of Sciences.