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Bacteria Make "Surface-to-air" missiles to shoot down our immune system

An introduction to bacterial IgA proteases, what are they and why we are studying them. Jon R Sayers & Peter J Artymiuk, University of Sheffield

The Battleground

Bacteria need moisture, the right temperature, degree of acidity and nutrients to grow. For these reasons, our mucous membrane i.e. mouths and nasal passages make great places for some bacteria to live and grow. Many types of bacteria colonize these relatively attractive environments without causing us any harm. Our bodies have developed specialized antibodies, defensive weapons generated by our immune systems. These antibodies are called immunoglobulin A, or IgA for short. They are shaped a bit like the letter Y and can catch invading bacteria, sticking them to each other so that they end up in large clumps. These clumps of bacteria then get caught in the mucous that our bodies secrete. The moist skin that lines the mouth and nasal passages is covered in small hair-like structures called cilia, they act like a brush, sweeping the clumps of bacteria up and out so that you can expel them. You will probably have noticed that when you have a throat infection you produce greenish coloured mucous. That is a combination of the bacteria, antibodies and various cells and chemicals that your immune system has used to defeat the invading bacteria. The overall process is known as immune exclusion.

Anti body  spinning
An antibody, showing the Y shape and red, sticky patches that can grab the surface of invading bacteria
Igap animated
The IgA protease, showing its teeth in red!

An Arms Race

Some bacteria have developed weapons that can cut our antibodies into small pieces so that they become unable to stick the invading bacteria into clumps. These anti-antibodies are called IgA proteases and are produced inside bacteria like the ones that cause meningitis and gonorrhoea. The bacteria make proteins inside their cells and then these proteins get secreted through the bacterium's surface. The protease can then attack the antibodies and allowing the bacteria to gain a foothold. These proteases also seem able to attack other human proteins and help the bacteria burrow through the skin and eventually into the bloodstream.

Studying the IgA Proteases

Several laboratories are studying these interesting bacterial proteins. Understanding how they work might give us new ways to fight these invaders in the never-ending battle between man and bacteria.  We make large quantities of these proteins so that we can try to determine their shape and structure, how that cut up antibodies and what other human proteins they might attack. The images on this page show what these strange molecules look like. They are pretty large by bacterial standards and seem to have a long stem, a protruding branch and a globular region that contains the teeth of the protease, the part that actually cuts up the antibodies.  We hope that studies on these unusual proteins might eventually lead to the development of new treatments or even vaccines against diseases such as meningitis and gonorrhoea.

Nano-engineering of IgA Proteases

Although the exact secretion pathway is not fully understood, we know that the protease is initially secreted using its own "launching platform" or secretion module which gets cut off as the protease reaches the outside of the bacterial cell. The IgA protease secretion pathway offers genetic engineers the possibility of modifying these bacterial proteases so that they can be made to work for us. The genes that form the blueprints for IgA protease can be made to work in harmless bacteria by hijacking the secretion launch platform, known as the beta core.  We can link the beta core to other proteins. Depending on what we link these beta cores to, so we end up with bacteria with unusual properties, for example, they may be able to absorb specific molecules like pollutants, or we could make the bacteria secrete useful proteins. These studies are ongoing in our and other laboratories.

Research in the Artymiuk & Sayers' labs is funded by

MRC

Meningitis Research Foundation

bbsrc

For more scientific and technical details click HERE

 

You can contact me via  j.r.sayers  (guess what goes here) shef.ac.uk