A walk into the LuxR regulators of Actinobacteria: phylogenomic distribution and functional diversity

Abstract

LuxR regulators are a widely studied group of bacterial helix-turn-helix (HTH) transcription factors involved in the regulation of many genes coding for important traits at an ecological and medical level. This regulatory family is particularly known by their involvement in quorum-sensing (QS) mechanisms, i.e., in the bacterial ability to communicate through the synthesis and binding of molecular signals. However, these studies have been mainly focused on gram-negative organisms, and the presence of LuxR regulators in the gram-positive Actinobacteria phylum is still poorly explored. In this manuscript, the presence of LuxR regulators among Actinobacteria was assayed using a domain-based strategy. A total of 991 proteins having one LuxR domain were identified in 53 genome-sequenced actinobacterial species, of which 59% had an additional domain. In most cases (53%) this domain was REC (receiver domain), suggesting that LuxR regulators in Actinobacteria may either function as single transcription factors or as part of two-component systems. The frequency, distribution and evolutionary stability of each of these sub-families of regulators was analyzed and contextualized regarding the ecological niche occupied by each organism. The results show that the presence of extra-domains in the LuxR-regulators was likely driven by a general need to physically uncouple the signal sensing from the signal transduction. Moreover, the total frequency of LuxR regulators was shown to be dependent on genetic, metabolic and ecological variables. Finally, the functional annotation of the LuxR regulators revealed that the bacterial ecological niche has biased the specialization of these proteins. In the case of pathogens, our results suggest that LuxR regulators can be involved in virulence and are therefore promising targets for future studies in the health-related biotechnology field.

Figure 1. Distribution of the LuxR-containing sequences retrieved from Actinobacteria according to their domain architecture.

REC, receiver domain; PAS, Per (period circadian protein), Arnt (Ah receptor nuclear translocator protein), Sim (single-minded protein); HDc, phosphohydrolase; AAA, ATPases associated with diverse cellular activities; CHD, cyclase homology domain; FHA, forkhead-associated domain; PKc, protein kinases catalytic domain; TPR, tetratricopeptide repeat domain; CSP_CDS, cold-shock protein with a S1-like cold shock domain.

Figure 2. Neighbor-Joining unrooted tree of all LuxR-containing sequences retrieved from Actinobacteria.

The branches colour refers to each protein architecture: LuxR are coloured in blue; REC+LuxR are coloured in red; CHD+LuxR are coloured in yellow; TPR+LuxR are coloured in light green; Pkc+LuxR are coloured in light pink; AAA+LuxR are coloured in light blue; LuxR+CSP_CDS are coloured in light red; FHA+LuxR are coloured in green; HDc+LuxR are coloured in pink; PAS+LuxR are coloured in brown; Pkc+TPR+LuxR are coloured in grey. With the exception of REC, the presence of these extra domains is highlighted in the figure.

Figure 3. Neighbor-Joining unrooted tree of all actinobacterial species considered in this study.

The domain composition and number of the LuxR proteins’ family in each species are mapped on the right.

Figure 4. Significant differences in the GO terms-based functional annotation of the LuxR regulators belonging to specific categories.

The GO terms shown in the graphs correspond to the most specific ones among those that were considered significant (i.e., with a p-value by False Discovery Rate control below 0.05).