A genetic disruption strategy developed by CU Boulder researchers effectively stymies the evolution of antibiotic-resistant bacteria such as E. coli, giving scientists a crucial leg up in the ongoing battle against deadly superbugs.
These multidrug-resistant pathogens—which adapt to current antibiotics faster than new ones can be created—infect nearly 2 million people and cause at least 23,000 deaths annually in the U.S., according to data from the Centers for Disease Control.
In an effort to develop a sustainable long-term solution, CU Boulder researchers created the Controlled Hindrance of Adaptation of OrganismS (CHAOS) approach, which uses CRISPR DNA editing techniques to modify multiple gene expressions within the bacteria cells, stunting the pathogen’s central processes and thwarting its ability to evolve defenses.
The findings are outlined today in the journal Communications Biology and could open new research avenues on how to best restrict a pathogen’s antibiotic resistance.
“We now have a way to cut off the evolutionary pathways of some of the nastiest bugs and potentially prevent future bugs from emerging at all,” said Peter Otoupal, lead author of the study and a doctoral researcher in CU Boulder’s Department of Chemical and Biological Engineering (CHBE).
The CHAOS research is the culmination of work that began in 2013, when Otoupal and his colleagues began searching for genes that could act as a cellular kill switch for E. coli. When the scientists tweaked one gene at a time, the bacteria could adapt and survive. But when they altered two or more genes at once, the cell got weaker.
“We saw that when we tweaked multiple gene expressions at the same time—even genes that would seemingly help the bacteria survive—the bacteria’s fitness dropped dramatically,” Otoupal said.
The CHAOS method takes advantage of this effect, pulling multiple genetic levers in order to build up stress on the bacterial cell and eventually trigger a cascading failure, leaving the bug more vulnerable to current treatments. The technique does not alter the bug’s DNA itself, only the expression of individual genes, similar to the way a coded message is rendered useless without the proper decryption.
“You can think of it in terms of a series of escalating annoyances to the cell that eventually cause it to weaken,” said Anushree Chatterjee, senior author of the study and an assistant professor in CHBE. “This method offers tremendous potential to create more effective combinatorial approaches.”
Although E. coli has nearly 4,000 individual genes, the exact gene modification sequence appears to matter less than the sheer number of genes that are disrupted, Otoupal said. Still, the researchers plan to continue optimizing the CHAOS method to seek out the most efficient disruptions.“Diseases are very dynamic, so we need to design smarter therapies that can gain control over their rapid adaptation rates,” Chatterjee said. “The emphasis in our lab is demonstrating the efficacy of these methods and then finding ways to translate the technology to modern clinical settings.”
“In the past, nobody really considered that it might be possible to slow down evolution,” Otoupal said. “But like anything else, evolution has rules and we’re starting to learn how to use them to our advantage.”
Learn more: How to stop an antibiotic-resistant superbug
The Latest on: Genetic disruption
[google_news title=”” keyword=”genetic disruption” num_posts=”10″ blurb_length=”0″ show_thumb=”left”]
via Google News
The Latest on: Genetic disruption
- What preceded the abrupt resignation of UB pediatrics chair?on March 26, 2023 at 3:00 am
Many believe the situation boiled over last month with Lipshultz's firing of leading clinical genetics expert Dr. Taosheng Huang, who made his displeasure over his termination without cause widely ...
- Genes known to control eye color are essential for retinal healthon March 24, 2023 at 6:05 am
Metabolic pathways consist of a series of biochemical reactions in cells that convert a starting component into other products.
- Disruption of the FcRn–IgG interaction may make AAV-based gene therapies effectiveon March 23, 2023 at 10:45 am
The use of a monoclonal antibody that reduced circulating IgG levels, led to a decrease in preexisting neutralizing antibodies (NAbs) to adeno-associated virus (AAV).
- Protein Found to Play a Role in Rare Genetic Immune Disorderson March 22, 2023 at 5:00 am
Researchers at the Garvan Institute of Medical Research report they have discovered a protein that plays a critical role in immune cell function is at the root of immunodeficiency disorders. PI3K ...
- Why experts recommend ditching racial labels in genetic studieson March 22, 2023 at 12:16 am
Race should no longer be used to describe populations in most genetics studies, a panel of experts says. Using race and ethnicity to describe study participants gives the mistaken impression that ...
- Insights into causes of rare genetic immune disorderson March 21, 2023 at 9:14 am
The cellular glitches underlying a rare genetic disorder called activated PI3K Delta syndrome 2 (APDS2) have been identified by researchers at the Garvan Institute of Medical Research. The disorder is ...
- Genetic causes of three previously unexplained rare diseases identifiedon March 16, 2023 at 9:10 am
New York, NY (March 16, 2023) – Using a new computational approach they developed to analyze large genetic datasets from rare disease cohorts, researchers at the Icahn School of Medicine at ...
- Talent Genetic Testing Market: The Growing Trend 2027on March 15, 2023 at 5:44 pm
Pre and Post Covid Report Is Covered | Final Report Will Add the Analysis of the Impact of Russia-Ukraine War and ...
- Invitae to Present Data at The American Clinical Genetics Meeting 2023 That Supports Removing Barriers to Genetic Testingon March 15, 2023 at 2:36 pm
the company's ability to use rapidly changing genetic data to interpret test results accurately and consistently; security breaches, loss of data and other disruptions; laws and regulations applicable ...
via Bing News