What goes around comes around: updates in the study of Coxiella burnetii lipopolysaccharide phase variation

Lipopolysaccharide (LPS) is a major outer membrane component of Gram-negative bacteria that can modulate host immune responses during infection. Extensive studies on the LPS of well-studied organisms, such as Escherichia coli and Salmonella spp., have elucidated many LPS pathways; however, knowledge of unique LPS structures of lesser-studied bacteria, such as Coxiella burnetii , remains limited. C. burnetii is an intracellular pathogen that is the cause of the zoonotic disease Q fever. The highly infectious nature of C. burnetii warrants designation as a select agent by the United States Federal Select Agent Program and must be contained in a Biosafety Level three facility. Contributing to the organism’s biothreat potential, C. burnetii LPS is a critical virulence determinant that dictates bacterial survival and pathogenesis. Several reviews have extensively covered C. burnetii LPS structure and function prior to 2017, though recent findings regarding mechanisms of LPS biosynthesis, LPS-induced host immunity, and LPS elongation pose biosafety and regulatory questions that necessitate careful consideration. Here, we discuss recent (post-2017) findings related to C. burnetii LPS from scientific and biosafety perspectives that may be applicable across many fields of research. From the discovery of C. burnetii LPS phase variation by Fiset and Stoker in 1956 to the recent elucidation of specific genetic mechanisms underlying this process, the study of C. burnetii LPS is a reminder that what goes around comes around, even in research.