The action of iron on local Klebsiella infection of the skin of the guinea-pig and its relation to the decisive period in primary infective lesions.

The infectivity of 16 strains of Klebsiella spp. and its modification by systemic and local ferric iron were tested in the skin of the guinea-pig. The in vivo proliferation of 11 strains was enhanced in varying degrees by Fe+++ (E + strains); 5 strains (Eo) were not enhanceable even by large doses of Fe+++. Of 10 strains examined in detail, 6 were E + and 4 were E0. Guinea-pig and human sera were consistently bacteriostatic for E + strains and bactericidal for Eo strains. Both Fe+++ and microbial iron-chelators abolished the bacteriostasis of E + strains but did not affect the lethal effect on Eo strains. Both effects were diminished by heating the sera to 56 degrees for 30 min and by the anticomplementary substance Liquoid; neither appeared to be due to specific antibody. Virulence, as measured in the skin and by intravenous injection, was roughly associated with degree of enhanceability by iron, the EO strains being among the least virulent. The volume of plasma exudate entering the skin during the first 5 h was sufficient to kill a large proportion of the infecting doses of Eo strains and to inhibit the growth of infecting doses of E + strains. Enhancement of the latter by Fe+++ is predominantly the result of inhibition of the non-specific bacteriostasis exerted by the extravascular plasma. Lesions by E + strains aged 4 h or more are insusceptible to systemic Fe+++ and only moderately susceptible to large doses of local Fe+++. The insusceptibility appears to be due to segregation of the infecting bacilli within exudate leucocytes. Klebsiella infections accordingly provide another example of an initial decisive period of action of the antibacterial defences-in this case non-specific and humoral-which cease to be locally effective after the first few hours. Besides enhancing lesions due to E + strains, systemic Fe+++ has an opposite, apparently anti-inflammatory action on klebsiella lesions, slightly decreasing their size. It was evident with all the strains tested, whether dead or alive, but not in E + lesions in circumstances when they were susceptible to enhancement by the Fe+++.