Quorum sensing inhibits interference competition among bacterial symbionts within a host

The symbioses that animals form with bacteria play important roles in health and disease, but the molecular details underlying how bacterial symbionts initially assemble within a host remain unclear.1-3 The bioluminescent bacterium Vibrio fischeri establishes a light-emitting symbiosis with the Hawaiian bobtail squid Euprymna scolopes by colonizing specific epithelium-lined crypt spaces within a symbiotic organ called the light organ.4 Competition for these colonization sites occurs between different strains of V. fischeri, with the lancet-like type VI secretion system (T6SS) facilitating strong competitive interference that results in strain incompatibility within a crypt space.5,6 Although recent studies have identified regulators of this T6SS, how the T6SS is controlled as symbionts assemble in vivo remains unknown.7,8 Here, we show that T6SS activity is suppressed by N-octanoyl-L-homoserine lactone (C8 HSL), which is a signaling molecule that facilitates quorum sensing in V. fischeri and is important for efficient symbiont assembly.9,10 We find that this signaling depends on the quorum-sensing regulator LitR, which lowers expression of the needle subunit Hcp, a key component of the T6SS, by repressing transcription of the T6SS regulator VasH. We show that LitR-dependent quorum sensing inhibits strain incompatibility within the squid light organ. Collectively, these results provide new insights into the mechanisms by which regulatory networks that promote symbiosis also control competition among symbionts, which in turn may affect the overall symbiont diversity that assembles within a host.