posted on 2020-11-11, 06:44authored byAyaka Yoshihara, Mika Shimatani, Megumi Sakata, Chika Takemura, Wakana Senuma, Yasufumi Hikichi, Kenji Kai
Strains
of Ralstonia solanacearum species complex
(RSSC) cause “bacterial wilt” on a wide range of plant
species and thus lead to marked economic losses in agriculture. Quorum
sensing (QS), a bacterial cell–cell communication mechanism,
controls the virulence of RSSC strains by regulating the production
of extracellular polysaccharide (EPS) and secondary metabolites, biofilm
formation, and cellular motility. R. solanacearum strain OE1-1 employs (R)-methyl 3-hydroxymyristate
(3-OH MAME) as a QS signal, which is synthesized by the PhcB methyltransferase
and sensed by the PhcS/PhcRQ two-component system. We describe the
design, synthesis, and biological evaluation of inhibitors of the phc QS system. Initial screening of a small set of QS signal
analogues revealed that methyl 3-hydroxy-8-phenyloctanoate, named,
PQI-1 (phcquorum sensing inhibitor-1), inhibited biofilm
formation by strain OE1-1. To improve its inhibitory activity, the
derivatives of PQI-1 were synthesized, and their QS inhibition activities
were evaluated. PQIs-2–5 evolved from PQI-1 more strongly inhibited
not only biofilm formation but also the production of ralfuranone
and EPS. Furthermore, RNA-Seq analysis revealed that the PQIs effectively
inhibited QS-dependent gene expression and repression in strain OE1-1.
On the other hand, the PQIs did not affect the canonical QS systems
of the representative reporter bacteria. These antagonists, especially
PQI-5, reduced wilting symptoms of the tomato plants infected with
strain OE1-1. Taken together, we suggest that targeting the phc QS system has potential for the development of chemicals
that protect agricultural crops from bacterial wilt disease.