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.

AguR, a Transmembrane Transcription Activator of the Putrescine Biosynthesis Operon in Lactococcus lactis, Acts in Response to the Agmatine Concentration

“…A high degree of structural homology was noted when the AguR intracellular LuxR_C-like domain was compared to the LuxR_C-like domains of LuxR family members with solved structures (Fig. 8); indeed, the characteristic four-␣-helix secondary structure for this domain was shared (53). Moreover, half of the amino acid residues of the LuxR_C-like domain (34 of 62 residues) were strongly conserved across all the compared structures, indicating a high degree of sequence conservation.…”

Complete Genome Sequence Analysis of Nocardia brasiliensis HUJEG-1 Reveals a Saprobic Lifestyle and the Genes Needed for Human Pathogenesis

“…LuxR regulators are a group of bacterial helix-turn-helix (HTH) transcription factors that are involved in the regulation of many bacterial quorum-sensing (QS) mechanisms [60]. N. brasiliensis has a LuxR system, including a putative two-component system response regulator of the LuxR family protein together with 23 transcriptional regulators.…”

A Human Lung-Associated Streptomyces sp. TR1341 Produces Various Secondary Metabolites Responsible for Virulence, Cytotoxicity and Modulation of Immune Response

“…Genes B, C, D, E, G, and H encode chain-tailoring enzymes (Figure 3). The cluster encodes the same three regulatory genes as in S. filipensis: FilR, a SARP-LAL regulator; FilF, a regulator from the PAS-LuxR family, which is involved in the regulation of virulence factors in pathogenic actinobacteria (Ryan et al, 2015) and finally FilI, a PadR family transriptional regulator (Santos et al, 2012;Vicente et al, 2014). An extra, perhaps incomplete, ORF encodes a short protein with another PAS domain.…”