The growing threat posed by bacteria certainly gives them some credit for their cleverness. Infections caused by Staphylococcus aureus drug-resistant strains kill 19,000 more Americans each year than HIV/AIDS victims. Antibiotic-resistant strains emerged 60 years ago, and since then scientists have been struggling to develop a second generation of drugs that attack not the bacteria - which promotes resistance - but their intracellular communication. Progress so far has been slow, as bacteria, againHowever, new proposals from social evolutionary biology finally point the way to overcome the cleverness of microorganisms exploiting certain members to destroy the whole group.
Forty years ago, scientists discovered that some bacteria send and receive messages - in the form of small molecules - to neighboring cells and vice versa. This type of communication, called perception of a quorum, allows bacteria to monitor their population density and adjust their behavior. When, in the vicinity, there are enough cells to create a quorum, the bacteria start producing proteins known as virulence factors that make their hosts sick. they can also grow in aggregates called biofilms, which make them up to a thousand times more resistant to antibiotics.
Jolla, California, calls this strategy the "covert approach." Antibiotics bind bacteria or prevent them from growing, which allows resistant mutants to thrive. Drugs that disrupt the perception of quorum However, they would spare the life of the microorganisms by simply preventing them from causing disease or building biofilms.
The problem is that good perception inhibitors quorum The molecules that bacteria use to communicate are often species-specific, so it is difficult to develop universal inhibitors. In addition, inhibitors that would work well in animals are shown to be toxic in humans. Some researchers are also concerned that these drugs are only effective early in theinfection, before a quorum As a result of these challenges, few pharmaceutical companies would invest in drugs based on a communications strategy: "People are a little cautious," says Helen Blackwell, a chemist at the University of Wisconsin-Madison.
In January, evolutionary biologist Stuart West and his colleagues at the University of Edinburgh, announced a new approach based on a known aspect of perception of a quorum : not all bacteria in a given population communicate normally. so-called blind mutants produce low-level signals but do not respond to them, while negative mutants respond to signals but cannot produce them.
These cheaters still benefit from the perception of a quorum because their neighbors collaborate, but they conserve a lot of energy compared to their mates. As a result, they thrive and reproduce rapidly, breeding new generations that contain increasingly larger proportions of mutants. Once they become dominant, communication becomes so rare that thepopulation cannot achieve a quorum and its virulence decreases.
West and colleagues infected a group of mice with Pseudomonas aeruginosa normal - a bacterium commonly associated with hospital infection - and infected two other groups with 50% normal 50% blind or negative Pseudomonas aeruginosa mixtures. Seven days later, the mice infected with the mixtures were twice as likely to survive as the mice infected with normal strains. "It sounds strange, but one might think that bycontracting an infection is introduced a social cheating mutant that facilitates the cure."
However, this therapy won't be available anytime soon, West says, mainly because it would be hard for people - and even harder for regulators - to accept the idea of stopping infections with more bacteria. Still, he and his colleagues have filed a patent application for the process and are also working on a "Trojan Horse"-related concept, which attempts to usemutants to introduce specific genes into the population. "Suppose we have an antibiotic-resistant infection; we make a cheat mutant susceptible to antibiotics spread, and soon the population can be treated with existing drugs."
Even if these strategies do not work, researchers in the field believe that more traditional inhibitors of perceived quorum will be successful.
Text taken from the magazine Science American (ANO 7. n°85. pg 20)