Sensitization of Gram-negative bacteria to antibiotics and complement by a nontoxic oligopeptide

Abstract

A major virulence factor of bacteria that cause generalized infections is their resistance to the lytic action of the complement cascade, an important defence mechanism of the host. Invasive Gram-negative enteric bacteria, which cause about one-third of all bacteraemic infections, are completely resistant to lysis by complement, even in the presence of hyperimmune serum. The same bacteria are also resistant to many antibiotics that are effective therapeutic agents against other bacteria, as the outermost surface layer (the outer membrane) of the bacteria functions as a permeability barrier. Here we show that it is possible to sensitize such bacteria to both complement and antibiotics by using an agent that binds to the outer membrane. This agent is a nontoxic derivative of polymyxin which by itself has no bactericidal action.