When bacteria fight back


Published on December 05, 2016

Some bacteria that cause disease in humans are becoming more resistant to antobiotics—so resistant that some experts see ‘antibiotic resistant’ infections as tomorrow’s plague. Fortunately, research is progressing, particularly at the UCL de Duve Institute.

Antibiotics are probably the greatest medical advance of the 20th century. Since the discovery of the first, penicillin, in 1928, they have saved millions of lives by attacking bacteria that are potentially pathogenic to humans. The problem is that all over the world more and more people are getting bacterial infections that resist one or several antibiotics. Some bacteria that were countered successfully for decades, such as E.coli and staphylococcus, hardly react to antibiotic treatment anymore. The result is that more people are dying from these diseases. And not only children, the elderly and patients already sick are susceptible. Even a healthy adult can catch an antibiotic-resistant infection.

équipe JF Collet

Resistance: an ancient and natural process

Resistance is far from new. In fact, it’s as old as the bacteria themselves, which appeared on earth long before we did. Over millennia, bacteria developed an extraordinary ability to adapt and survive. ‘For example, some have pumping systems that expel toxic substances’, explains Prof. Jean-François Collet, a researcher at UCL’s de Duve Institute and a bacteria specialist. ‘They can also communicate with each other and share their tricks! And since they reproduce very quickly, sometimes in 20 minutes, it’s enough for one helpful mutation to occur in a single bacterium for this same mutation to spread rapidly throughout an entire bacterial population.’ 

In short, like all life, bacteria have a survival instinct and defend themselves against their attackers, among them antibiotics. ‘Every time an antibiotic has gone on the market,’ continues Prof. Collet, ‘some years later resistance started to occur.’ How? ‘An antibiotic attacks a specific target, a protein on the surface or inside the bacterium. The gene containing this protein’s code (or ‘identity card’) can mutate and result in a protein that’s indifferent to the antibiotic. When this happens, the antibiotic no longer recognises its original target and fails to destroy the bacterium. This is one of the mechanisms that can drive antibiotic resistance.’

The bacterium: a little fortress

Antibiotic resistance is a problem because for a long time we haven’t discovered any new ones. ‘The pharmaceutical industry lost interest. Yet it takes 10 to 15 years of research to develop a new antibiotic’. In his laboratory, Prof. Collet and his student team study the defence mechanisms of gram-negative bacteria.1 The goal is to discover how to override these mechanisms and identify new targets for future antibiotics.

To understand their research, it’s useful to think of a gram-negative bacterium as a little fortress consisting of:

  • two fortified enclosures, i.e. the two membranes that surround and protect the bacterium against external attacks;
  • the bacterium’s headquarters;
  • soldiers, i.e. proteins inside the bacterium that can sometimes come out to fight attackers;
  • masons, i.e. proteins inside the bacterium that can repair holes in the fortified walls.

‘In 2014, we discovered that the bacterium has an alarm system that alerts headquarters when there’s a hole or breach in one of the enclosures’,2 explains Prof. Collet. ‘This allows the bacterium to dispatch its little masons to repair it. We’re currently developing molecules that could sabotage this alarm system and therefore impair the bacterium’s ability to defend itself.’ 

Bacteria vs. bleach

In late 2015, in collaboration with the Université d’Aix-Marseille, Prof. Collet published an article in the prestigious journal Nature on another defence mechanism of bacteria.3 ‘Bleach (sodium hypochlorite) is a powerful antibacterial substance’, he explains. ‘Some of our cells are capable of producing it. This natural bleach can attack the bricks (proteins) that make up the bacterium’s fortified enclosure. We’ve discovered that when this happens, certain bacteria trigger a system that repairs the bricks damaged by bleach, which allows them to survive the attack.’ Such a discovery, like those before it, might lead to new antibiotics. 

Candice Leblanc.

(1) There are two main families of bacteria: gram-positive have a single protective membrane, gram-positive have two.

(2) This discovery was featured in the scientific journal Cell.

(3) Gennaris et al., ‘Repairing oxidized proteins in the bacterial envelope using respiratory chain electrons’, in Nature, December 2015.

Prof. Collet’s research on bacteria is or has been financed mainly by the FNRS, the WELBIO Institute, and a grant from the European Research Council (ERC).

A Glance at Jean-François Collet's bio

  1995                       Master’s Degree in Agricultural Sciences Engineering (UCL)
1995-2000                Doctoral Thesis (UCL, de Duve Institute)
2001-2004                Post-doctorate (University of Michigan, US)
2004                         Winner of the Belgian Royal Academy of Sciences Prix Fredericq
                                 Winner of the Belgian American Educational Foundation Award
2005-2013               FNRS Research Associate, de Duve Institute (UCL)
2010                        Winner of the Belgian Royal Academy of Medicine Prix Alvarenga de Piauly,
                                Winner of the Prix De SomerSince
2011                         Investigator, WELBIO Institute
Since 2013               Head of FNRS Research and Professor, UCL
2014                        Winner of Belgian Royal Academy of Medicine Prix Henri Fauconnier