Antibiotic resistance is one of the major societal challenges of this moment. When targeting viability (e.g. with antibiotics), resistant cells have a very high fitness advantage over susceptible cells and as a consequence, resistance is spreading rapidly. Because of that, the BAM group at CMET (prof. Tom Defoirdt) is investigating another approach: targeting activity. One of the mechanisms that control activity of bacteria is quorum sensing, bacterial cell-to-cell communication with small signal molecules. These systems control the production of molecules and cell structures pathogenic bacteria need to attack their host (i.e. virulence factors) and because of that, the inhibition of quorum sensing is intensively investigated as a novel strategy to control bacterial infections.

A key question with respect to the application of quorum sensing inhibition is whether it will impose selective pressure for the spread of resistance. The general assumption in the field for a long time was that quorum sensing inhibition would exert minimal selective pressure, making the development of resistance unlikely. This was based on the observation that quorum sensing is not essential for the fitness of bacteria. We have challenged this assumption because it was based on experiments conducted in nutrient-rich synthetic growth media, where quorum sensing is indeed not essential. We argued that the situation might be different during infection of a host since quorum sensing controls virulence factor production, which enables pathogens to obtain nutrients in the host environment. 

In order to obtain a meaningful indication of what will happen with pathogens in a host, the spread of resistance should be studied in the environment where it ultimately matters: during multiple cycles of infection of a host and transmission to a new host. Recently, Qian Yang, postdoc at CMET, investigated the spread of resistance to quorum sensing inhibition in populations of the quorum sensing model pathogen Vibrio campbellii  during up to 35 cycles of infection and transmission. She found that resistance did not spread if the initial frequency of the resistance was low, whereas it further increased to 100% if it was already prevalent. However, even in the latter case, the resistance spread at a much slower pace than resistance to antibiotics spread in the same infection model.

Here is the full story: https://academic.oup.com/ismej/article/18/1/wrae251/7926933

A discussion of the implications can be found here: https://www.tandfonline.com/doi/full/10.1080/19490976.2025.2476582