LuxR Solos are Becoming Major Players in Cell-Cell Communication in Bacteria

The most common quorum sensing (QS) system in Gram-negative bacteria occurs via N-acyl homoserine lactone (AHLs) signals. An archetypical system consists of a LuxI-family protein synthesizing the AHL signal which binds at quorum concentrations to the cognate LuxR-family transcription factors which then control gene expression by binding to specific sequences in target gene promoters. QS LuxR-family proteins are approximately 250 amino acids long and made up of two domains; at the N-terminus there is an autoinducer-binding domain whereas the C-terminus contains a DNA-binding helix-turn-helix (HTH) domain. QS LuxRs display surprisingly low similarities (18-25%) even if they respond to structurally similar AHLs. 95% of LuxRs share 9 highly conserved amino acid residues; six of these are hydrophobic or aromatic and form the cavity of the AHL-binding domain and the remaining three are in the HTH domain. With only very few exceptions, the luxI/R cognate genes of AHL QS systems are located adjacent to each other. The sequencing of many bacterial genomes has revealed that many proteobacteria also possess LuxRs that do not have a cognate LuxI protein associated with them. These LuxRs have been called orphans and more recently solos. LuxR solos are widespread in proteobacterial species that possess a canonical complete AHL QS system as well as in species that do not. In many cases more than one LuxR solo is present in a bacterial genome. Scientists are beginning to investigate these solos. Are solos responding to AHL signals? If present in a bacterium which possesses a canonical AHL QS system are solos an integral part of the regulatory circuit? Are LuxR solos eavesdropping on AHLs produced by neighboring bacteria? Have they evolved to respond to different signals instead of AHLs, and are these signals endogenously produced or exogenously provided? Are they involved in interkingdom signaling by responding to eukaryotic signals? Recent studies have revealed that LuxR solos are involved in several mechanisms of cell-cell communication in bacteria implicating them in bacterial intraspecies and interspecies communication as well as in interkingdom signaling by responding to molecules produced by eukaryotes. LuxR solos are likely to become major players in signaling since they are widespread among proteobacterial genomes and because initial studies highlight their different roles in bacterial communication. This Research Topic allows scientists studying or interested in LuxR solos to report their data and/or express their hypotheses and thoughts on this important and currently understudied family of signaling proteins

The commensal microbiota exacerbate infectious colitis in stressor-exposed mice

Exposure to a prolonged restraint stressor disrupts the colonic microbiota community composition, and is associated with an elevated inflammatory response to colonic pathogen challenge. Since the stability of the microbiota has been implicated in the development and modulation of mucosal immune responses, we hypothesized that the disruptive effect of the stressor upon the microbiota composition directly contributed to the stressor-induced exacerbation of pathogen-induced colitis. In order to establish a causative role for stressor-induced changes in the microbiota, conventional mice were exposed to prolonged restraint to change the microbiota. Germfree mice were then colonized by microbiota from either stressor-exposed or non-stressed control mice. One day after colonization, mice were infected with the colonic pathogen, Citrobacter rodentium. At six days post-infection, mice that received microbiota from stressor-exposed animals had significant increases in colonic pathology and pro-inflammatory cytokine (e.g. IL-1β) and chemokine (e.g. CCL2) levels after C. rodentium infection in comparison with mice that received microbiota from non-stressed mice. 16S rRNA gene sequencing revealed that microbial communities from stressed mice did not have any detectable Bifidobacterium present, a stark contrast with the microbial communities from non-stressed mice, suggesting that stressor-induced alterations in commensal, immunomodulatory Bifidobacterium levels may predispose to an increased inflammatory response to pathogen challenge. This study demonstrates that the commensal microbiota directly contribute to excessive inflammatory responses to C. rodentium during stressor exposure, and may help to explain why gastrointestinal disorders are worsened during stressful experiences. Keywords: Psychosocial stress; Microbiota gut brain axis; Colitis; Citrobacter; Social disruption; Mucosal immunity; MicrobiomeNational Institutes of Health (U.S.) (Grant RO1AT006552

Time-resolved multi-omics illustrates host and gut microbe interactions during Salmonella infection.

Salmonella infection, also known as Salmonellosis, is one of the most common food-borne illnesses. Salmonella infection can trigger host defensive functions, including an inflammatory response. The provoked-host inflammatory response has a significant impact on the bacterial population in the gut. In addition, Salmonella competes with other gut microorganisms for survival and growth within the host. Compositional and functional alterations in gut bacteria occur because of the host immunological response and competition between Salmonella and the gut microbiome. Host variation and the inherent complexity of the gut microbial community make understanding commensal and pathogen interactions particularly difficult during a Salmonella infection. Here we present metabolomics and lipidomics analyses along with 16s rRNA sequence analysis, revealing a comprehensive view of the metabolic interactions between the host and the gut microbiota during Salmonella infection in a CBA/J mouse model. We found that different metabolic pathways were altered over the four investigated time points of Salmonella infection (days -2, +2, +6, and +13). Furthermore, metatranscriptomics analysis integrated with metabolomics and lipidomics analysis facilitated an understanding of the heterogeneous response of mice depending on the degree of dysbiosis