Effects of synthetic protease inhibitors of the amidine type on cell injury by Rickettsia rickettsii

David Walker, R. R. Tidwell, T. M. Rector, J. D. Geratz

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

To evaluate the importance of proteolytic activity in the pathogenesis of cell injury by Rickettsia rickettsii, a series of four aromatic amidine inhibitors of trypsin-like proteases were introduced into the plaque model. The compounds were shown to be active toward plaque reduction with their order of effectiveness parallel to their antitrypsin activity. One of the compounds, bis(5-amidino-2-benzimidazolyl)methane, at a concentration of 10-5 M demonstrated complete inhibition of plaque formation on day 6. Bis(5-amidino-2-benzimidazolyl)methane at the same concentration reduced cell injury even when added to the system after 72 h of rickettsial infection. The reduction in morbidity in guinea pigs experimentally infected with R. rickettsii and treated with bis(5-amidino-2-benzimidazolyl)methane as compared with morbidity in infected, untreated animals, comprised delay in the onset of fever and slightly fewer febrile animals. Because bis(5-amidino-2-benzimidazolyl)methane had no effect on phospholipase A2, the enzyme activity associated with penetration-induced cell injury, it is likely that a trypsin-like protease also plays an essential role either in the physiology of R. rickettsii or as its pathogenic mechanism.

Original languageEnglish (US)
Pages (from-to)582-585
Number of pages4
JournalAntimicrobial Agents and Chemotherapy
Volume25
Issue number5
StatePublished - 1984
Externally publishedYes

Fingerprint

Rickettsia rickettsii
Amidines
Protease Inhibitors
Wounds and Injuries
Peptide Hydrolases
Fever
Morbidity
Trypsin Inhibitors
Phospholipases A2
Trypsin
Guinea Pigs
bis(5-amidino-2-benzimidazolyl)methane
Enzymes
Infection

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Effects of synthetic protease inhibitors of the amidine type on cell injury by Rickettsia rickettsii. / Walker, David; Tidwell, R. R.; Rector, T. M.; Geratz, J. D.

In: Antimicrobial Agents and Chemotherapy, Vol. 25, No. 5, 1984, p. 582-585.

Research output: Contribution to journalArticle

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