An evolutionary perspective of endotoxin: a signal for a well-adapted defense system

In the evolutionary view of endotoxin presented here, endotoxin is the primary signal animals use to detect gram negative (Gr-) bacteria. Since endotoxin, or lipopolysaccharide (LPS), is an integral part of the surface of all Gr- bacteria, it was excellent evolutionary 'choice' for the signal. The concept of an 'endotoxin response system' (ERS) is introduced. The ERS protects against Gr- bacteria by employing many of the body's defenses to both detect and react against LPS. The intensity of the response has evolved to maximize protection while minimizing the biological cost and self-damaging effects. The setting of the response, here termed the 'endostat', is programmed by natural selection and fine tuned by feedback mechanisms. Other potentially invasive organisms are detected by different signals, but the effector components of the defenses are similar. This evolutionary view of LPS offers a framework for the seemingly contradictory findings on endotoxin and suggests new avenues of productive research.