Bacterial proteinases as targets for the development of second-generation antibiotics

Biochim Biophys Acta. 2000 Mar 7;1477(1-2):35-50. doi: 10.1016/s0167-4838(99)00278-2.


The emergence of bacterial pathogen resistance to common antibiotics strongly supports the necessity to develop alternative mechanisms for combating drug-resistant forms of these infective organisms. Currently, few pharmaceutical companies have attempted to investigate the possibility of interrupting metabolic pathways other than those that are known to be involved in cell wall biosynthesis. In this review, we describe multiple, novel roles for bacterial proteinases during infection using, as a specific example, the enzymes from the organism Porphyromonas gingivalis, a periodontopathogen, which is known to be involved in the development and progression of periodontal disease. In this manner, we are able to justify the concept of developing synthetic inhibitors against members of this class of enzymes as potential second-generation antibiotics. Such compounds could not only prove valuable in retarding the growth and proliferation of bacterial pathogens but also lead to the use of this class of inhibitors against invasion by other infective organisms.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Amino Acid Sequence
  • Anti-Bacterial Agents / metabolism*
  • Bacteria / enzymology*
  • Bacteria / pathogenicity
  • Drug Design
  • Drug Resistance, Microbial
  • Endopeptidases / metabolism*
  • Molecular Sequence Data
  • Periodontitis / immunology
  • Periodontitis / microbiology
  • Porphyromonas gingivalis / enzymology
  • Porphyromonas gingivalis / pathogenicity
  • Protease Inhibitors / metabolism*


  • Anti-Bacterial Agents
  • Protease Inhibitors
  • Endopeptidases