Nucleases of bacterial pathogens as virulence factors, therapeutic targets and diagnostic markers

Int J Med Microbiol. 2019 Dec;309(8):151354. doi: 10.1016/j.ijmm.2019.151354. Epub 2019 Aug 30.

Abstract

New frontiers of therapy are being explored against the upcoming bacterial diseases rendered untreatable due to multiple, extreme and pan- antibiotic resistance. Nucleases are ubiquitous in bacterial pathogens performing various functions like acquiring nucleotide nutrients, allowing or preventing uptake of foreign DNA, controlling biofilm formation/dispersal/architecture, invading host by tissue damage, evading immune defence by degrading DNA matrix of neutrophil extracellular traps (NETs) and immunomodulating the host immune response. Secretory nucleases also provide means of survival to other bacteria like iron-reducing Shewanella and such functions help them adapt and survive proficiently. Other than their pro-pathogen roles in survival, nucleases can be used directly as therapeutics. One of the powerful armours of pathogens is the formation of biofilms, thus helping them resist and persist in the harshest of environments. As eDNA forms the structural and binding component of biofilm, nucleases can be used against the adhering component, thus increasing the permeability of antimicrobial agents. Nucleases have recently become a model system of intense study for their biological functions and medical applications in diagnosis, immunoprophylaxis and therapy. Rational implications of these enzymes can impact human medicine positively in future by opening new ways for therapeutics which have otherwise reached saturation due to multi drug resistance.

Keywords: Bacterial nucleases; Biofilm; Diagnosis; Drug target; Vaccine; Virulence.

Publication types

  • Review

MeSH terms

  • Animals
  • Bacteria / drug effects
  • Bacteria / enzymology*
  • Bacteria / pathogenicity
  • Bacterial Infections / diagnosis*
  • Bacterial Infections / drug therapy
  • Bacterial Proteins / metabolism*
  • Biofilms
  • Biomarkers
  • Deoxyribonucleases / metabolism*
  • Drug Discovery
  • Humans
  • Mice
  • Virulence Factors / metabolism*

Substances

  • Bacterial Proteins
  • Biomarkers
  • Virulence Factors
  • Deoxyribonucleases