UCL de Duve Institute researchers discovered that bacteria have a defence against our immune system’s bleach. Could this lead to new antibiotics?
To defend itself against the many attacks to which it’s subjected each day, our body uses a set of a defence mechanisms known as the immune system. It wages all-out war on the microorganisms (pathogenic bacteria, viruses, etc.) that seek to harm us. ‘When a bacterium attacks our body, the immune system’s first response is to deploy cells, or “immune soldiers”’, explains Prof. Jean-François Collet, a de Duve Institute researcher and bacteria specialist. ‘These tiny soldiers produce and bombard the enemy bacterium with oxidising substances that destroy it.’1
Different, and differently armed, soldiers exist. Neutrophils, for example, can produce sodium hypochlorite, better known as bleach. It’s a powerful antibacterial agent because it oxidises and destroys parts of the bacterial cell, including its surrounding membranes. ‘Bacterial membrane is composed of hundreds of proteins, like bricks in a perimeter wall’, continues Prof. Collet. ‘Almost all proteins contain sulphur, an atom that oxidises very easily. When neutrophil-soldiers spray bleach at the bacterium, it’s like shooting a flame-thrower. The protein-brick catches fire, and the fire spreads. Soon, if nothing’s done, many proteins are neutralised, a breach forms in the perimeter wall and the bacterium malfunctions. Such an attack can eventually kill it.’
When the bacterium fights back
But the bacterium doesn’t necessarily let that happen. It has several defence mechanisms, acquired over millions of years of evolution, that can help it resist, for example, antobiotics.2 Prof. Collet’s team, in collaboration with the team of Prof. Frédéric Barras of the Université Aix-Marseille and the National Center for Scientific Research (France, CNRS), set out to understand why and how certain bacteria survive bleach attacks.3 ‘For two years, all our efforts failed, because bacteria are lazy: unless attacked by bleach, they don’t activate the mechanism that interests us and thus we couldn’t find it’, says Prof. Collet. ‘So we had to force their hand.’
Uncovering a new defence system
To do so, researchers first genetically modified E. coli4 bacteria by stripping them of their known bleach defence systems. Next, they placed them in extreme conditions, similar to a ‘fire’, but without bleach. The experience was fatal to several, but not all, the bacteria. Confronted with the choice to live or die, some E. coli activated a special defence system called MsrPQ. ‘It produces proteins that act simultaneously as firefighters and masons. First they put out the fire. Then they repair the damage.’ This allows the bacterium to continue normal function, maintain its perimeter wall, and survive the offensive.
Progress in the fight against antibiotics resistance
This discovery was reported in the December 2015 issue of the prestigious scientific journal Nature.5 Essentially, the MsrPQ system could be a new target of future antibiotics. ‘Previous research and studies showed that bacteria which no longer have an MsrPQ system are less virulent and more vulnerable’, explains Prof. Collet. ‘So our goal is to find a molecule capable of preventing the MsrPQ system from deploying. Like a tool that lets us lock the garage or garrison of the firefighter-masons, which would help our immune system soldiers to defeat pathogenic bacteria.’
(1) One well-known oxidation phenomenon is rust, the effect of oxygen on iron. (2) See the Antibiotic resistance article (lien hypertexte ?). (3) In 2011, researchers received a grant from the European Research Council to conduct this research. (4) Escherichia coli, or E. coli, is an intestinal bacterium very common among humans. (5) Gennaris et al., ‘Repairing oxidized proteins in the bacterial envelope using respiratory chain electrons’, Nature, December 2015. Prof. Collet’s research on bacteria are or have been funded mainly by the FNRS, the WELBIO Institute and a grant from the European Research Council (ERC).
A glance at Jean-François Collet's bio