Dec. 16 (UPI) -- Antibiotic resistance has been called a public health crisis.
Now, researchers at the University of California San Diego School of Medicine may have identified a new weapon against these deadly bugs, using the powerful CRISPR gene editing tool, called Pro-AG. Their findings were published Monday in the journal Nature Communications.
In 2018, the Organization for Economic Co-operation and Development estimated that, by 2050, more than one million Americans will have died from infections caused by antibiotic-resistant bacteria. According to the U.S. Centers for Disease Control and Prevention, already nearly three million such infections are diagnosed nationwide each year, and they claim the lives of at least 35,000 people annually.
While Pro-AG is not yet ready for treating patients, "a human delivery system carrying Pro-AG could be deployed to address conditions such as cystic fibrosis, chronic urinary infections, tuberculosis and infections associated with resistant biofilms that pose difficult challenges in hospital settings," said Victor Nizet, distinguished professor of pediatrics and pharmacy and head of the Collaborative to Halt Antibiotic-Resistant Microbes at UC San Diego, said in a statement.
Over-prescribing antibiotics, as well as their use in animal food production, have led to a rising prevalence of resistant bacteria in the environment. Research has shown that these environmental sources of antibiotic resistance are passed along to humans, contributing to the current health crisis.
CRISPR, or Clustered Regularly Interspaced Short Palindromic Repeats, are repeating sequences of genetic code interrupted by so-called spacer sequences, which are remnants of genetic code from past invaders. First discovered in 2013, researchers now believe CRISPRs are fundamental parts of the immune system that help the human body fight off invading viruses.
In the years since, they have become a fundamental part of genome editing technology that can be programmed to target specific stretches of genetic code to edit DNA at precise locations.
The Pro-AG, or pro-active genetic system, is just the latest example of this technology being put into practice. Developed by UC San Diego researchers, it is a CRISPR-based gene-drive system that enables the inactivation of the gene renders bacteria antibiotic resistant by leveraging technology designed to foster inheritance of preferred traits called "active genetics."
According to the UC San Diego team, Pro-AG features a modification of the standard CRISPR-Cas9 gene editing technology. Working with Escherichia coli bacteria, the researchers were able to use it to disrupt the function of plasmids, circular forms of DNA that replicate independently of the bacterial genome.
Multiple copies of plasmids carrying antibiotic-resistant genes can exist in each cell and effectively transfer antibiotic resistance between bacteria. Pro-AG uses a cut-and-insert repair mechanism to disrupt the activity of the antibiotic resistant gene with at least two orders of magnitude greater efficiency than current cut-and-destroy methods.
In the Nature Communications paper, the authors demonstrated the effectiveness of the new technique in experimental cultures containing a high number of plasmids carrying genes known to confer resistance to the antibiotic ampicillin. With the Pro-AG, they were able to insert tailored genetic payloads into target sites with high precision to disrupt the resistance process.
The authors believe the technology could one day be used to treat chronic bacterial infections or to clear environments such as sewers, fish ponds and animal feedlots of antibiotic-resistant bacteria. Because Pro-AG "edits" genes -- rather than destroy them -- the technology may also enable the engineering or manipulating bacteria for a broad range of future biotechnological and biomedical applications by rendering them harmless.
"The highly efficient and precise nature of Pro-AG should permit a variety of practical applications, including dissemination of this system throughout populations of bacteria using one of several existing delivery systems to greatly reduce the prevalence of antibiotic resistance in the environment," said Ethan Bier, science director of the UC San Diego unit of the Tata Institute for Genetics and Society.