Scientists can see how bugs infect cells in detail

Researchers at the University of Bristol have discovered a new approach for studying molecules within their natural environment.

The research, led by a team of biochemists, microbiologists and physicists, provides an unprecedented level of detail of the consequences of a bacterium approaching another cell, directly in situ.

Until now, traditional approaches to understanding infection have focused on either studies of the cells involved or dissection of individual molecules.

Leo Brady, professor of biochemistry and Mumtaz Virji, professor of molecular microbiology, have developed a novel method for bridging these, until now, separate approaches.

The team studied the common bacterium Moraxella catarrhalis, which causes middle ear infections in young children, and is a major cause of morbidity in those with heart disease.

For many years, scientists approached this problem from the molecular medicine approach – through isolating and studying proteins from the Moraxella cell surface that initiate infection. From these studies the team have been able to develop an overview of one of the key proteins, UspA1.

However, this model has been based on studies of the UspA1 protein in isolation, rather than in its natural setting on the bacterium surface.

A common worry for many biomedical scientists is how such understanding translates into the reality of these tiny molecules when they are part of a much larger cell. Understanding the increased complexity of individual molecules is crucial to understanding why many promising drugs fail to live up to expectations.

To begin bridging this gap in understanding, professors Brady and Virji teamed up with Dr Massimo Antognozzi from the university’s school of physics, whose group has been developing a novel form of atomic force microscope, termed the lateral molecular force microscope.

Together, they have evolved the design of the microscope to optimise its ability to measure biological phenomena such as changes in UspA1 directly at the Moraxella cell surface.

The microscope differs from more conventional atomic force microscopes in tapping samples against an extremely fine lever, rather than moving the lever as is usually the case.

Prof Brady said: “The findings have triggered the development of a novel technology that promises to open up a new approach for studying molecular medicine.”