Quorum sensing (QS) is the ability of microbes to sense and respond to their own population
density, which typically results in cooperative activity (Fuqua et al., 1994). This
form of microbial communication is important to agriculture and human health as they
often participate in the regulation of genes important for host interactions.
The classic example of QS in bacteria is performed by the symbiotic bioluminescent
bacterium Vibrio fischeri (Hastings and Greenberg, 1999). This bacterium colonizes
the light organ of a squid and becomes luminescent at high population density. A pheromone
of the acylhomoserine lactone class (AHL) is synthesized by the enzyme LuxI, and is
a proxy for population density. The AHL is sensed by the transcription factor LuxR,
which then activates the transcription of the luxICDABEG luciferase operon. Homologous
LuxR-LuxI pairs have been found throughout the Proteobacteria (Fuqua et al., 2001);
there is divergence among the structures of AHLs produced and detected by LuxI-LuxR
pairs, providing some species specificity to the systems.
Several studies and the sequencing of many bacterial genomes has evidenced the presence
of many AHL/QS-related luxR-type genes, which are unpaired to a cognate luxI. These
LuxRs possess the typical modular structure having an AHL-binding domain and a DNA-binding
HTH domain. These upaired luxRs/LuxRs have been called orphans (Fuqua, 2006; Patankar
and Gonzalez, 2009) and more recently solos (Subramoni and Venturi, 2009). Several
questions arise on the role of LuxR solos in bacteria and recent studies have revealed
a number of roles including eavesdropping, intra-species and inter-kingdom signaling.
This research topic of Frontiers in Cellular and Infection Microbiology is a collection
of 10 articles which highlight these different roles as well as the widespread distribution
of LuxR solos.
Three articles highlight how widespread LuxR solos are and provide data on their phylogenetic
distribution (Gan et al., 2014; Hudaiberdiev et al., 2015; Subramoni et al., 2015).
These surveys have shown the presence of one or multiple predicted LuxR solos in many
proteobacterial genomes living in different environments, some of them also harboring
genes for one or more complete AHL-QS circuits. LuxR solos can be tentatively clustered
into meaningful groups or putative orthologs. These LuxR solos subfamilies could respond
to different signals and/or having different roles.
The functions of solos can thus far be sub-divided in four categories; as detecting
endogenous or exogenous signals, of either the classical AHL type, or of a novel type.
The AHL-responsive solos can firstly detect exogenous AHLs, i.e., AHLs synthesized
by other organisms, and this category is typified by the LuxR solo, SdiA (Sperandio,
2010; Soares and Ahmer, 2011; Swearingen et al., 2013; Sabag-Daigle et al., 2015).
Orthologs of sdiA are present in Escherichia, Salmonella, Enterobacter, Citrobacter,
Cronobacter, Klebsiella, Pantoea, and Erwinia (Sabag-Daigle and Ahmer, 2012). The
Pantoea and Erwinia orthologs are part of luxR-luxI pairs and represent the ancestral
state, and the luxI homolog was lost in the remaining genera, giving rise to the sdiA
solos (Sabag-Daigle and Ahmer, 2012). In this issue, an sdiA-regulon study is presented
showing a number of genes regulated by SdiA in Enterobacter cloacae (Sabag-Daigle
et al., 2015). Interestingly some target genes were regulated in the complete absence
of AHLs and thus AHLs may not be a “folding-switch” for SdiA, in which SdiA only folds
correctly in the presence of AHL (Yao et al., 2006; Nguyen et al., 2015), AHL may
alter the DNA binding specificity of SdiA so that there are AHL-dependent and AHL-independent
promoters. LuxR solos can also be used to detect endogenous AHLs, i.e., AHLs that
are made by the species detecting them. This “third wheel” type of LuxR solo is typified
by QscR of Pseudomonas aeruginosa which harbors two complete AHL QS circuits, namely
LasI/R and RhlI/R (Chugani and Greenberg, 2014; Martínez et al., 2015). In this issue,
a review regarding the function of QscR is presented (Chugani and Greenberg, 2014;
Martínez et al., 2015). QscR is involved in virulence and it responds to LasI generated
AHLs, however it has a more relaxed specificity and is more promiscuous than LasR
and its regulon overlaps with the one of LasR. The article particularly focuses on
its biochemistry since QscR has become a model for understanding QS LuxR homologs.
LuxR solos can also respond to ligands which are not AHLs of either endogenous or
exogenous sources. A large sub-family of LuxR solos has been found that specifically
recognizes molecules from plants (González and Venturi, 2012; da Silva et al., 2015;
Xu et al., 2015). These solos are only found in both pathogenic and beneficial plant-associated
bacteria (PAB) and show changes in one or two highly conserved amino acids of the
autoinducer binding domain (González and Venturi, 2012). Another member of this subfamily
of PAB LuxR solos is reported in this Frontiers topic (Xu et al., 2015) as well as
studies of protein domain switching between these solos and classic AHL responsive
motifs (da Silva et al., 2015). A major step forward will be to identify the class
of plant molecules that these solos respond to. Some solos respond to an endogenous,
non-AHL, ligand. The LuxR-type receptor PluR of Photorhabdus luminescens responds
to α-pyrones, while the related organism Photorhabdus asymbiotica responds to dialkylresorcinols
using the LuxR homolog PauR (Brachmann et al., 2013; Brameyer et al., 2014, 2015;
Brameyer and Heermann, 2015; Chen et al., 2015). The synthases for these molecules
were determined to be PpyS and DarABC, respectively. In this instance, the LuxR solos
turned out not to be solo at all. Instead, these LuxR homologs are paired with previously
unrecognized types of synthases. In this topic, a survey of these LuxRs in Photorhabdus
species is reported (Brameyer et al., 2014).
In summary, LuxR solos are widespread in Proteobacteria hence they are major players
in bacterial communication and require more attention. Articles in this topic highlight
the different modes of action of LuxR solos which are responding to endogenous and
exogenous AHL or non-AHL signals. Further studies could lead to novel ways of controlling
bacterial host colonization.
Conflict of interest statement
The authors declare that the research was conducted in the absence of any commercial
or financial relationships that could be construed as a potential conflict of interest.