Human infection with an unusual corynebacterium

Mutational loss of pesticin I, a bacteriocin-like substance produced by Pas- teurella pestis, is known to result in concomitant loss of a coagulase and fibrino- lytic factor.No relationship was detected between pesticinogeny and other tested properties either associated with virulence or peculiar to P. pestis.Pesticin I was distinguished from the coagulase and fibrinolytic activities on the basis of ana- tomical distribution, behavior during gel filtration, and sensitivity to heat.Coagu- lase and the fibrinolytic factor were not differentiated by these criteria.Spontaneous suppressor mutations causing reversion to pesticinogeny were not detected, nor were such mutants obtained by treatment with ultraviolet light or 2-aminopurine.Attempts to demonstrate a common activator of pesticin I, coagulase, or the fibrino- lytic factor in extracts of pesticinogenic cells were not successful.These results are in accord with the hypothesis that at least two structural genes for the three ac- tivities reside on a replicon distinct from the chromosome proper.Fibrinolytic ac- tivity was significantly reduced in the presence of 0.003 M e-aminocaproic acid and was nonexistent on fibrin films freed from endogenous plasminogen by treatment with heat.Fibrinolytic activity on heated films could be restored by addition of plasma or serum from six mammalian species.Accordingly, the plague fibrinolytic factor, like staphylokinase or urokinase, promotes the conversion of plasminogen to plasmin.Most workers agree that Pasteurella pestis, the causative agent of bubonic plague, and P. pseu- dotuberculosis are very closely related species.Nevertheless, these organisms are easily distin- guished by the symptoms of the disease that they cause as weU as by their invasiveness or ability to initiate a generalized infection from an intra- dermal or subcutaneous site of injection.For example, P. pseudotuberculosis most commonly causes a mild and localized mesenteric lymphadenitis in man (20, 26) that bears little resemblance to plague, an acute and frequently fatal infection.P. pestis is highly virulent in rats, which are generally resistant to infection with P. pseudotuberculosis.Both species are virulent in guinea pigs provided that the organisms are injected intraperitoneally; only P. pestis can infect this host after abrasion of the skin (31).The LD5o for P. pestis in Swiss-Webster mice (Fort Detrick strain) was less than 10 cells when injected by the 1 Preliminary reports of portions of this work were presented at the Annual Meeting of the American Society for Microbiology, Cleveland, Ohio, June 1963, and at the Symposium on Bacteriocins and Bac- teriocin-like Substances held at Gottingen, Germany, October 1964.19 intravenous, intraperitoneal, or subcutaneous routes; that for P. pseudotuberculosis approached this value only after intravenous injection (6).Accordingly, only P. pestis seems capable of consistent initiation of a generalized infection from peripheral sites of injection.The ability probably reflects the fact that P. pestis, but not P. pseudotuberculosis, is infectious by fleabite, the normal process whereby plague is transmitted in nature.Both species can survive in fleas (5, 31).Pseudotuberculosis, however, is probably acquired after ingestion of the organisms (29).Another difference between the two species is the presence of fibrinolytic (25) and coagulase (18) activities in P. pestis.A correlation between expression of the fibrinolytic factor (F) and coagulase (C) was reported by Domaradskii (11), who failed to detect either activity in P. pseudo- tuberculosis.Brubaker, Surgalla, and Beesley (9) subsequently noted that production of F and C is correlated with production of pesticin I (PI), a bacteriocin-like substance active against P. pseudotuberculosis (4, 7, 8, 14, 35).The presence of PI, F, and C in P. pestis might account in part for the general distinctions between plague and pseudotuberculosis.This possibility received Vol.94, No.