IBM researchers tout potential key to reversing antibiotic resistance

Using laboratory automation methods, IBM researchers deployed unique synthesis methods to rapidly generate different potential polymers to be combined with therapeutics, allowing the testing of options for increasing antibiotic strength.

IBM has published research that it touts could hold the key to reversing antibiotic resistance.

"Since the discovery of penicillin in 1928, antibiotics have transformed the world of medicine. They have prevented the spread of disease, saved countless lives, and curbed the effects of infectious epidemics," IBM said.

"Unfortunately, antibiotics have also frequently been misused, which has led to one of the largest threats to global health, food security, and development: Antibiotic resistance."

In a blog post, IBM explained that a new strategy to increase antibiotic potency and reverse drug resistance has proven necessary in mitigating antibiotic resistance. It also said that as the antibiotic development pipeline has run dry since the 1980s, with few new antibiotics being approved for clinical use -- and at the same time, bacteria has grown stronger -- the availability of new drugs that can fight bacteria is failing to keep up.  

Based on a decade of studying with antimicrobial experts from Singapore's Institute of Bioengineering and Nanotechnology (IBN), IBM researchers have designed a new macromolecule that they believe could dramatically transform the effectiveness of antibiotics.

Big Blue said this newly created polymer could fight new, stronger, and emerging bacterial strains, such as the six ESKAPE pathogens largely responsible for the majority of serious hospital-acquired infections.

The researchers explained that when this polymer is combined with existing antibiotics, the drugs significantly improved their ability to kill pathogenic bacteria by targeting biomolecules within the bacteria that have become stronger.

Adding to its potential, IBM said the polymer proved it could combine with other therapeutics -- such as anti-tuberculosis and anti-rheumatic drugs -- to be repurposed to effectively fight resistant bacterial infections. 

"Typically brought on by sublethal doses of drugs, antibiotic resistance develops when bacteria modify enzymes, proteins, or genes. This polymer attaches itself to cytosolic enzymes responsible for those modifications, enabling the drug to bypass protective measures and take effect as intended," IBM explained.

"In this new research, when the polymer combines with a number of existing antibiotics, it reduces the required effective dose to levels equal or below amounts used for much weaker strains -- proving it can significantly strengthen drugs to successfully fight serious and lethal infections. And if less antibiotics are needed, the lesser chance bacteria are given the chance to evolve and strengthen."

The IBM researchers deployed unique synthesis methods to rapidly generate different potential polymers by using automation. They generated up to 100 distinct polymers in nine minutes. IBM said they could serve as viable options to be combined with therapeutics.

"This allowed the combined IBM and Singapore Institute team to quickly test and explore a wide range of options for increasing antibiotic strength, iterating until the most effective polymer was designed," it added.

"Based on its current performance in the lab, this polymer could hold significant promise for how existing antibiotics are used, and for slowing the proliferation of serious illnesses such as pneumonia, tuberculosis, hospital-acquired infections, and sepsis syndromes."

Working with this polymer created by IBM Research, scientists from IBN discovered that these polymers showed no onset of resistance after many sub-lethal treatments due to a unique mechanism that included membrane translocation followed by precipitation of cytosolic biomacromolecules. 

Additionally, IBM said multiple treatments with the polymer neither increased the effective dose nor upregulated expression of genes associated with resistance, as evidenced by RNA sequencing performed by scientists from A*STAR's Genome Institute of Singapore (GIS). 

Scientists from IBN, GIS, and Singapore-MIT Alliance for Research and Technology (SMART) discovered that the polymer/rifampicin combination worked synergistically to mediate rapid and significant cytosolic stress in bacteria, and this played a final effector role in bacterial cell death after treatment with the combination. 

Researchers are now exploring how this same approach to polymer creation and drug combination can be used for other challenges, such as chemotherapeutic resistance. 

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