Cell-cell signaling in Haloferax volcanii: how archaea communicate

About This Grant

Project Summary Archaea are important members of the human microbiome, are crucial for global nitrogen and carbon cycles, and have extensive applications in biotechnology and bioremediation. Yet, many important aspects of archaeal cell biology remain poorly understood. One such aspect our lab has focused on and successfully contributed to for over two decades is the understanding of the archaeal cell surface. Using the model archaeon Haloferax volcanii, we have elucidated many of the mechanisms involved in the biogenesis of the cell wall and motility structures, as well as cell surface related activities such as biofilm formation. Our recent work has also shown that significant changes in Hfx. volcanii morphology and motility occur in response to changes in population density. This suggests the involvement of quorum sensing (QS), a type of intercellular communication wherein microbes detect and respond to population density, in archaeal morphology and motility regulation. Despite the widespread bacterial utilization of QS for intra- and inter-species communication, our knowledge of archaeal extracellular signaling molecules and the associated molecular machineries for biogenesis and response is lacking. Thus, our observations provide a unique opportunity to study archaeal QS. Our preliminary data suggest that Hfx. volcanii secretes a small signaling molecule(s) that accumulate as population density increases, triggering a novel QS-response pathway that results in phenotypic changes. Building on these data, we will use an interdisciplinary approach to identify the QS signaling molecule(s) and the molecular machineries that synthesize, recognize, and respond to these signals. Our approach combines forward and reverse genetics, phenotypic assays, analytical chemistry, and multi-omics studies to produce the first comprehensive network of a QS system in Archaea. This regulatory network will serve as a launching point for a broader research program aimed at uncovering the molecular mechanisms that govern QS-associated physiological processes—including cell shape transitions, motility regulation, and biofilm development—and at defining how archaeal cells integrate multiple signaling inputs to coordinate complex behaviors. Since archaea exist in diverse microbial communities alongside bacteria, we will also investigate the potential for inter-domain communication by determining whether Hfx. volcanii signaling molecule(s) activate or quench bacterial QS systems. Thus, our studies will illuminate both conserved and domain-specific principles of microbial communication, broaden our understanding of archaeal roles in complex microbial communities such as the human microbiome, and support future applications of archaeal physiology in medicine, microbial ecology, and biotechnology.