The human complement system sensitizes Gram-negative bacteria for Gram-positive-specific antibiotics via pore formation in the outer membrane

Abstract

This article focuses on major characteristics of the complement system and complement regulatory proteins. Emphasis will be on the following essential questions: (a) How does the complement system activate and amplify? (b) How does the complement system recognize self (host) vs non-self (i.e. pathogens or altered self) in order to induce inflammatory processes, promote phagocytosis, and/or kill pathogens in a targeted manner? (c) What are the main functions of complement in innate and adaptive immunity? (d) How do complement regulatory proteins protect host from complement-mediated damage? (e) How are the main primary or secondary deficiencies, or loss or gain-of-function mutations in the components and regulatory proteins of complement associated to severe infections and/or other diseases? (f) What are the current FDA-approved therapeutics to protect patients from complement-mediated damage? and (g) How are complement protein levels and functions assessed in the clinic? The profound biomedical relevance of the complement system is illustrated through understanding the molecular mechanisms of the pleiotropic functions of this system, how it is regulated, and how it can lead to disease. It is this same understanding that allows for the identification and development of effective therapies, as well as how and when to best apply them.