Texas A&M team examines 'billions of years' of bacteria adaptation strategies

Texas A&M University researchers have delved into the energy mechanisms that enable bacteria to survive antibiotics, providing crucial insights into antibiotic resistance.

“Bacteria have developed numerous adaptation strategies over billions of years to survive in adverse environments,” said Pushkar Lele, associate professor in the Artie McFerrin Department of Chemical Engineering at Texas A&M, according to Texas A&M Today. “Most mechanisms of adaptation are yet to be understood.”

The groundbreaking study titled “Heterogeneous distribution of proton-motive force in nonheritable antibiotic resistance,” supported by the National Institute of Allergy and Infectious Diseases, was published in January in the American Society for Microbiology's mBio Journal. 

Bacteria have long been a formidable adversary in the battle against infectious diseases, with antibiotic resistance presenting a growing global concern.

While genetic resistance mechanisms are well known, the researchers have expanded the understanding of bacterial survival strategies beyond genetic adaptations and explored the electrochemical energies that fuel bacterial growth and their role in fostering antibiotic tolerance. 

Contrary to expectations, the team discovered that dormant bacterial cells, lacking sufficient energy, were often able to survive lethal doses of antibiotics as the antibiotics targeted processes that were stalled in these cells.

They were was taken aback when they observed actively swimming cells of Escherichia coli (E coli) surviving in the presence of antibiotics, suggesting that high energy levels played a role in their survival. This finding challenges the notion that high energy levels are detrimental to bacterial survival and highlights the adaptability of bacteria in the face of antibiotics.

The team also investigated how these surviving bacteria responded to decreasing levels of antibiotics when the treatment was prematurely halted. They discovered that cells with high energy levels resumed growth immediately once the antibiotic threat was removed, underscoring the risks of incomplete antibiotic courses. 

Such bacteria, armed with their energy reserves, possess the ability to swim away from harmful environments and propagate rapidly, further complicating the challenge of combating antibiotic resistance.

Lele suggests that the energy source responsible for bacterial motility, such as the rotation of flagella, also powers transporters called efflux pumps. These pumps can actively remove antibiotics from bacterial cells, mitigating the threat posed by the drugs. The observed swimming cells, likely adapted through this mechanism, further emphasize the diverse strategies bacteria employ to survive antibiotic stress.

The implications of this research are significant, as it sheds light on the resilience of bacteria in the face of antibiotics and the need for more comprehensive treatment approaches. The team's findings suggest that bacterial cells, with high energy levels, have a higher likelihood of survival when antibiotics are switched, highlighting the importance of considering the diversity of bacterial responses in treatment regimens. 

Understanding the energy dynamics of antibiotic-resistant bacteria could pave the way for the development of more effective strategies to combat antibiotic resistance and improve patient outcomes.

In addition to Lele, the project included the collaboration of other Texas A&M University members, including Annie H. Lee, Rachit Gupta, Hong Nhi Nguyen, Isabella R. Schmitz, and Deborah A. Siegele.