Stopping bacteria from talking to each other could help prevent serious infections say scientists from Aberdeen, in new research presented Monday at the Society for General Microbiology’s 155th Meeting at Trinity College Dublin.
“It is war out there. Bacteria need to wait until there are enough of them to attack us, otherwise they just get beaten off by our skin, the antibodies which patrol our blood, and our other defences,” says Professor Andrew Porter from Aberdeen University spin-out company Haptogen. “They use tiny molecules called haptens to talk to each other, letting each other know how many of them there are, much in the same way that we can smell things to sense what is going on in the world around us.”
“If we can block the actions of the haptens then we can fool the bacteria into thinking that there aren’t enough of them to attack us,” says Prof Porter. “The problem is that haptens are such tiny molecules that they don’t trigger our normal immune defences - they are so small they are invisible to our early warning radar.”
Infectious diseases are major killers - second only to heart diseases, infections cause a quarter of all the deaths in the world. Amongst other groups intensive care patients, cystic fibrosis patients and people suffering severe burns are particularly vulnerable. Now increases in world trade and travel mean that infectious diseases and antimicrobial-resistant strains of bacteria can spread rapidly between continents. Drug resistance, which is slow to reverse, costs lives, livelihoods and money, and threatens to undermine the effectiveness of many global health programmes.
The scientists believe that by targeting their signalling molecules instead of the bacteria themselves, they can avoid building up drug-resistant strains of bacteria. Haptens are used by bacteria to exchange information about numbers of bacteria, and to coordinate changes in their virulence just before they attack. Changing to their more dangerous state is costly for bacteria, and makes them more vulnerable to counter attack - in the same way that coming out from a defensive bunker to fire a weapon makes soldiers more vulnerable to enemy fire.
“If we can find a way of encouraging our bodies to produce antibodies which can wipe out these hapten signals, we can block the bacteria’s sensing and monitoring systems,” says Prof Porter. “Our early results suggest that we can make effective antibodies that not only stop the bacteria becoming more dangerous, they confuse communication so much that the bacteria commit suicide in their millions.”
The results so far from pre-clinical studies suggest that they have already found important prototype antibodies against the haptens. These can block the cell-to-cell signalling of Pseudomonas aeruginosa, a bacterium which particularly attacks the lungs of cystic fibrosis patients, transplant recipients and burns victims, killing one in three people with severe infections. This high death rate is partly due to the resistance that Pseudomonas bacteria have already built up to current antibiotics.