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Chemical Interrogation of LuxR-type Quorum Sensing Receptors Reveals New Insights into Receptor Selectivity and the Potential for Interspecies Bacterial Signaling
journal contribution
posted on 2017-08-22, 00:00 authored by Joseph
P. Gerdt, Danielle M. Wittenwyler, Joshua B. Combs, Michelle E. Boursier, Jacob W. Brummond, He Xu, Helen E. BlackwellCell–cell
signaling between bacteria, including quorum-sensing
(QS) communication systems, may play a role in the establishment and
maintenance of polymicrobial communities. To better understand and
model these interactions, we must uncover the degree to which neighboring
species recognize each another’s signals. In the current study,
we tested the likelihood of whether the QS systems of two opportunistic
pathogens (Acinetobacter baumannii and Pseudomonas
aeruginosa) that frequently arise in polymicrobial infections
would be affected by the QS signals of neighboring species. Through
the synthesis and screening of a library of native and non-native N-acyl l-homoserine lactones (AHLs), we found that
the AbaR LuxR-type receptor protein of A. baumannii is highly selective for its native AHL signal. However, a homologous
LuxR-type receptor in P. aeruginosa, LasR, is far
more promiscuously activated by AHLs relative to AbaR, suggesting
that LasR-regulated QS could be more susceptible to activation by
neighboring species. To explain the observed difference in signal
selectivity between AbaR and LasR, we developed a model based on (i)
the activity profiles of these proteins and (ii) previously reported
structural data and activity profiles for related LuxR-type receptors.
This model may facilitate the study of signal selectivities for hundreds
of LuxR-type QS receptors from bacteria, many of which grow in polymicrobial
communities and may sense each other’s signals. In addition,
we discovered a set of AHLs that could be used to selectively activate
LasR and selectively inhibit AbaR in polymicrobial experiments.