LETHAL EFFECT OF COMPLEMENT AND LYSOZYME ON POLYMYXIN-TREATED, SERUM-RESISTANT GRAM-NEGATIVE BACILLI

When genetically serum-resistant Escherichia coli, Klebsiella pneumoniae, and Citro-bacter freundii, but not Pseudomonas aeruginosa or Proteus mirabilis, were exposed to polymyxin B, they became susceptible to the bactericidal action of normal human and rabbit sera. In contrast, β-lactam and aminoglycoside antibiotics did not render any serum-resistant bacteria serum-sensitive. Synergy between polymyxin B and the serum bactericidal system could be demonstrated by the addition of polymyxin B to bacteria in vitro, as well as to bacilli in serum from rabbits injected with the antibiotic. Polymyxin B-treated bacteria were killed by normal, lysozyme-depleted, C2-deficient, and hypo-gammaglobulinemic sera, but not by heated or C6-deficient sera. These findings indicate that polymyxin B-treated bacteria can be killed via the alternative complement pathway. However, C3 and C3b were detected on the surface of serum-resistant E. coli, regardless of whether the bacteria had been treated with polymyxin B. This observation suggests that a change in susceptibility to the alternative complement pathway was not the only explanation for the acquired serum sensitivity. Polymyxin B may also affect a step in the complement sequence beyond the activation of C3, a step that is apparently blocked in serum-resistant gram-negative bacteria. © 1979 by The University of Chicago.