Bacterial Enzyme Blueprint 'Lit' useful in fighting against Infection, new study claims

A team of scientists has discovered the molecular blueprint of Lit, one of the most important bacterial enzymes that plays a "stealthy" role in the development of infections by suppressing the immune response.

Drug designers can use blueprints like this to find potential flaws in bacterial arsenals as they work to develop novel medicines that could help us win the war on antibiotic resistance.

The research, led by Trinity College Dublin academics from the School of Biochemistry and Immunology and the Trinity Biomedical Sciences Institute (TBSI), was recently published in the prestigious international journal Nature Communications.

The involvement of lipoproteins in bacterial infection

It has been found that lipid proteins have a wide range of roles in bacterial cells. The host requires some of these proteins to survive, and others play an important role in its innate immune system.

The newly found Lit (lipoprotein intramolecular transacylase), which produces a unique lipoprotein that "cools the immune response," adds to the growing list of lipoprotein-building enzymes, raising the possibility that Lit allows bacteria to obtain a stealthy foothold in the host.

The study's senior author is Professor Martin Caffrey, Fellow Emeritus (Trinity and TBSI). He emphasised its importance and potential societal influence by saying:

"We believe Lit is very likely a virulence factor, negatively impacting host immune response to infection. As such, it could well turn out to be an important target for the development of critically needed antibiotics against which resistance is much less likely to evolve. And it is no exaggeration to say that antibiotic resistance poses a genuine, growing threat to our society.

"With a high-resolution crystal structure and a strong foundation for understanding how it functions in bacterial cells, we are in a similar position to where we were four years ago when we published similar work concerning a related lipoprotein processing enzyme, known as lipoprotein signal peptidase II (or LspA). LspA is currently under intense scrutiny as an antibiotic target by several research groups - including ours in TBSI - and by a number of pharmaceutical companies."