Bacterial Metalo-Aminopeptidases as Targets in Human Infectious Diseases

Abstract

Background: Human infectious diseases caused by bacteria are a worldwide health problem due to the increased resistance of these microorganisms to conventional antibiotics. For this reason, the identification of novel molecular targets and the discovery of new antibacterial compounds are urgently required. Metalo-aminopeptidases are promising targets in bacterial infections. They participate in crucial processes for bacterial growth and pathogenesis, such as protein and peptide degradation to supply amino acids, protein processing, access to host tissues, cysteine supply for redox control, transcriptional regulation, site-specific DNA recombination, and hydrogen sulfide production. Although several of these enzymes are not essential, they are required for virulence and maximal growth in conditions of nutrient limitation and high temperatures.

Objective: In this review, we describe the structural, functional, and kinetic properties of some examples of bacterial metalo-aminopeptidases, in the context of their use as antibacterial targets. In addition, we present some inhibitors reported for these enzymes.

Conclusion: It is necessary to conduct a meticulous work to validate these peptidases as good/bad targets and to identify inhibitors with potential therapeutic use.

Keywords: Antibacterial agents; divalent metallic cations; enzyme-inhibitor complexes; metalo-aminopeptidases; pathogenic bacteria; protease inhibitors.