Scientists have developed a bacterial enzyme that supposedly suppresses the immune response

Scientists have produced the first detailed molecular blueprints of a bacterial enzyme known as Lit, which is believed to play a “stealth” role in the progression of infection by reducing the immune response.

Such models allow drug designers to uncover potential weaknesses in bacterial arsenals as they seek to develop new therapies that can help us win the war on antibiotic resistance.

The study, led by scientists from the School of Biochemistry and Immunology and Trinity Biomedical Sciences Institute (TBSI) at Trinity College Dublin, has just been published by a leading international journal. Nature Communication.

Lipoproteins and their role in bacterial infection

Lipoproteins perform various functions in the bacterial cell. Some are essential for survival while others play an important role in engaging in the host’s innate immune response.

The growing list of enzymes responsible for building lipoproteins includes the recently discovered Lit (intramolecular lipoprotein transacylase), which creates a specific lipoprotein that “cools the immune response” – increasing the likelihood that Lit will allow the bacteria to stealthily implant. in the host. .

In an effort to understand how Lit works at the molecular level, the team led by Trinity has just produced the all-important high-resolution crystal structure of Lit from Bacillus cereus, a common bacterium found in soil and plants. food.

Combined with other analytical techniques, molecular dynamics simulations, and quantum mechanical approaches, the team now has a detailed understanding of how it works.

Professor Martin Caffrey, Fellow Emeritus (Trinity and TBSI), is the lead author of the research. Emphasizing its importance and potential impact on society, he said:

“We believe that Lit is most likely a virulence factor, negatively impacting the host’s immune response to infection. As such, it may well prove to be an important target for the development of essential antibiotics against which resistance is much less likely to evolve And it is no exaggeration to say that antibiotic resistance is a real and growing threat to our society.

“With a high-resolution crystal structure and a solid basis for understanding how it works in bacterial cells, we are in a similar position to where we were four years ago when we published similar work on an enzyme-processing enzyme. Related lipoproteins, known as signal lipoproteins. peptidase II (or LspA). LspA is currently under intense scrutiny as an antibiotic target by several research groups, including our own at TBSI, and by a number of pharmaceutical companies.