Researchers at the Indian Institute of Technology (IIT) Roorkee have identified a novel mechanism of antibiotic resistance in Escherichia coli (E. coli), offering potential new strategies to combat drug-resistant infections. The study, published in ACS Infectious Diseases, highlights the role of a specific bacterial protein in the development of resistance to mecillinam, a common antibiotic used to treat urinary tract infections (UTIs).
The global threat of antibiotic resistance is escalating, with projections estimating 10 million deaths annually by 2050 due to drug-resistant infections. This surpasses even cancer-related deaths, underscoring the urgent need for innovative approaches to counteract bacterial resistance.
The IIT Roorkee team focused on E. coli, a prevalent cause of UTIs, and discovered that the bacterial protein LD-transpeptidase A (LdtA) is pivotal in enabling bacteria to resist the effects of mecillinam. Mecillinam, a beta-lactam antibiotic, targets the bacterial cell wall to combat infection. The study revealed that when LdtA is present in high amounts, E. coli can develop resistance to mecillinam.
LdtA's Role in Resistance
The researchers found that LdtA helps bacteria evade the effects of 'rod complex targeting antibacterials', including mecillinam. This discovery suggests that targeting LdtA could restore the effectiveness of mecillinam and similar antibiotics.
"Our research brings us closer to dismantling the defences bacteria use to evade antibiotics," said Ranjana Pathania, lead researcher and a professor at IIT Roorkee's bioscience and bioengineering department. "This breakthrough is a vital step toward developing smarter and more resilient treatment strategies to protect global health and preserve the power of antibiotics for future generations."
Overcoming Resistance
During the study, researchers exposed E. coli to a newly developed rod complex protein targeting compound, IITR07865, for 30 days. This exposure led to mutations that increased the bacteria's resilience. These mutations, coupled with the overproduction of LdtA, rendered the bacteria resistant not only to IITR07865 but also to mecillinam.
The findings suggest that a combination therapy approach, using mecillinam in conjunction with inhibitors of LdtA, could be a viable strategy to combat antibiotic resistance in UTIs caused by E. coli. This approach aims to disable the bacteria's defense mechanism, making them susceptible to the antibiotic once again.
"With these insights, researchers can now explore combined treatments to make antibiotics more effective, ultimately protecting us from infections that might otherwise become untreatable," the institute said in a statement.
