Weak selection for resistance to quorum sensing inhibition during multiple host infection cycles

Abstract

Quorum sensing inhibition is a promising novel approach to control bacterial infections. However, it is not clear whether quorum sensing inhibition will impose selective pressure for the spread of resistance against quorum sensing inhibition in pathogen populations. Previous research tried to answer this question by using synthetic growth media, and this revealed that whether or not resistance will spread completely depends on the environment in which it is studied. Therefore, the spread of resistance should be studied in the environment where it ultimately matters: in vivo during infection of a host. Here, using quorum sensing inhibitor-susceptible and -resistant mimics, we show that resistance to quorum sensing inhibition does not spread in host-associated populations of Vibrio campbellii during up to 35 cycles of infection and transmission if the initial frequency of the resistance is low in the pathogen population, whereas it further increases to 100% if it is already prevalent. However, even in the latter case, the resistance spreads at a slower pace than resistance to antibiotics spreads under the same conditions.