Ratiometric Quorum-Sensing: Only transfer antibiotic resistance when the chances of success are high

Antibiotic-resistant pathogens are the next big threat to global health. Many resistant bacteria can transform antibiotic-susceptible individuals into resistant ones by a process known as conjugation or plasmid-mediated horizontal gene transfer (HGT), where the genes providing the resistance are passed directly from one individual to another in the form of a plasmid — a circular piece of DNA– after a close contact occurs between cells. Controlling such « bacterial sex » is key to develop counterstrategies against antibiotic-resistant pathogens.

In a study done at the CRI Collaboratory (Systems Engineering and Evolution Dynamics Laboratory INSERM U1284, University of Paris) –now published in PLoS BiologyAlvaro Banderas and Ariel Lindner, along with CRI students Arthur Carcano, Elisa Sia and Shuang Li, show that the pathogenic bacterium Enterococcus faecalis controls HGT by « estimating » how successful such transfer will be before actually investing energy in it. For a successful transfer, a cell carrying the plasmid must first encounter a susceptible one. An estimation of transfer success is based on a process called ratiometric quorum-sensing, where resistant individuals count the numbers of nearby susceptible ones by « smelling » their pheromones, but also count their own number by doing the same with their own specific, self-produced pheromone. Using the two pieces of information, cells can then estimate the ratio of resistant to susceptible bacteria and ignore changes in the total population size. Distinguishing between these two population-parameters (ratio and population size) is crucial, as only the former is a strong indicator of the likelihood of a successful encounter. Simply knowing just the number of either of the two types (resistant or susceptible) is not enough, as it does not describe the probability that that a randomly encountered cell is a susceptible one – ratio however does. As it occurs in yeasts and higher sexual organisms, determining this likelihood is crucial because activation of mating responses, as well as mating itself, is a very costly process. Furthermore, the authors predict that ratiometric quorum-sensing evolves because it confers the highest fitness (total numbers of resistant bacteria in the population) compared to other possible sensory strategies, while at the same time allowing susceptible bacteria to coexist in the same niche. This might hold the key to the design of probiotic strategies to control resistant infections.

Read the full paper here: https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000814

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