LPS in gram-negative bacterial growth and physiology: outside but fully integrated.

SUMMARYFor single-celled organisms, the cell envelope is the thin barrier between life and death, responding dynamically to both the ever-expanding self and the ever-changing environment. Failure to balance these responses can lead to disastrous consequences, such as lysis. In gram-negative bacteria, the cell envelope is tripartite, consisting of two lipid bilayers with the periplasm, an aqueous space containing the thin peptidoglycan sacculus, between them. The outer of these lipid bilayers-aptly called the outer membrane-is asymmetric, bearing phospholipids on the inner leaflet and lipopolysaccharide (LPS) on the outer leaflet. Surface-exposed, highly immunoreactive, and essential to nearly all tested gram-negative bacteria, the overall architecture of LPS is largely conserved, but its modifications are subject to a myriad of variations. LPS has been studied extensively for its roles in pathogenesis and immunobiology and as a target of potential novel antibiotics. However, LPS exists in both free-living and pathogenic bacteria, suggesting it plays a critical role in bacterial physiology independent of the host. This aspect of LPS biology and its contribution to overall gram-negative cell physiology remains an area of active investigation. Addressing this gap, here we describe recent work detailing the essential contributions of LPS to bacterial physiology: particularly its role in cell envelope rigidity, its contributions to outer membrane capacity and fluidity, and the mechanisms integrating LPS synthesis into diverse aspects of cell envelope biogenesis during growth and division. We end with a discussion of the subset of gram-negative organisms that survive-either naturally or through genetic manipulation-in the absence of LPS and the adaptations that make this possible.