Detecting Gramnegative bacteria Invariant molecules specific to different classes of microbes, but not expressed by eukaryotic cells, alert the immune system to a potential invader. Gaudet et al. identified one such molecule expressed by a variety of Gram-negative bacteria: the monosaccharide heptose-1,7-bisphosphate (HBP) (see the Perspective by Brubaker and Monack). HBP is an intermediate in the synthesis of lipopolysaccharide, a major component of bacterial cell walls. Rather than alerting the immune system through traditional pathogen detection pathways, such as Toll-like receptors, HBP signals through the host protein TIFA (TRAF-interacting protein with forkhead-associated domain), which activates both innate and adaptive immune responses to control the infection. Science , this issue p. 1251 ; see also p. 1207