Molecular Targets and Strategies for Inhibition of the Bacterial Type III Secretion System (T3SS); Inhibitors Directly Binding to T3SS Components

Biomolecules. 2021 Feb 19;11(2):316. doi: 10.3390/biom11020316.

Abstract

The type III secretion system (T3SS) is a virulence apparatus used by many Gram-negative pathogenic bacteria to cause infections. Pathogens utilizing a T3SS are responsible for millions of infections yearly. Since many T3SS knockout strains are incapable of causing systemic infection, the T3SS has emerged as an attractive anti-virulence target for therapeutic design. The T3SS is a multiprotein molecular syringe that enables pathogens to inject effector proteins into host cells. These effectors modify host cell mechanisms in a variety of ways beneficial to the pathogen. Due to the T3SS's complex nature, there are numerous ways in which it can be targeted. This review will be focused on the direct targeting of components of the T3SS, including the needle, translocon, basal body, sorting platform, and effector proteins. Inhibitors will be considered a direct inhibitor if they have a binding partner that is a T3SS component, regardless of the inhibitory effect being structural or functional.

Keywords: anti-virulence; antibacterials; inhibition; type III secretion system.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenosine Triphosphatases / chemistry
  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Outer Membrane Proteins / genetics*
  • Bacterial Proteins / genetics*
  • Cytoplasm / metabolism
  • Genomic Islands
  • Gram-Negative Bacteria / genetics*
  • Humans
  • Molecular Chaperones / chemistry
  • Peptides / chemistry
  • Periplasm / metabolism
  • Protein Binding
  • Protein Domains
  • Protein Transport
  • Salmonella
  • Type III Secretion Systems / metabolism*
  • Virulence*

Substances

  • Anti-Bacterial Agents
  • Bacterial Outer Membrane Proteins
  • Bacterial Proteins
  • Molecular Chaperones
  • Peptides
  • Type III Secretion Systems
  • Adenosine Triphosphatases