Mycobacteriophage putative GTPase-activating protein can potentiate antibiotics

Appl Microbiol Biotechnol. 2016 Sep;100(18):8169-77. doi: 10.1007/s00253-016-7681-7. Epub 2016 Jun 27.

Abstract

The soaring incidences of infection by antimicrobial resistant (AR) pathogens and shortage of effective antibiotics with new mechanisms of action have renewed interest in phage therapy. This scenario is exemplified by resistant tuberculosis (TB), caused by resistant Mycobacterium tuberculosis. Mycobacteriophage SWU1 A321_gp67 encodes a putative GTPase-activating protein. Mycobacterium smegmatis with gp67 overexpression showed changed colony formation and biofilm morphology and supports the efficacy of streptomycin and capreomycin against Mycobacterium. gp67 down-regulated the transcription of genes involved in cell wall and biofilm development. To our knowledge, this is the first report to show that phage protein in addition to lysin or recombination components can synergize with existing antibiotics. Phage components might represent a promising new clue for better antibiotic potentiators.

Keywords: Antibiotic potentiator; Antimicrobial resistance; Biofilm; GTPase-activating protein; Mycobacteriophage.

MeSH terms

  • Antitubercular Agents / pharmacology*
  • Capreomycin / pharmacology*
  • GTP Phosphohydrolase Activators / metabolism*
  • GTPase-Activating Proteins / genetics
  • GTPase-Activating Proteins / metabolism*
  • Mycobacteriophages / enzymology*
  • Mycobacteriophages / genetics
  • Mycobacterium smegmatis / drug effects*
  • Mycobacterium smegmatis / genetics
  • Mycobacterium smegmatis / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Streptomycin / pharmacology*

Substances

  • Antitubercular Agents
  • GTP Phosphohydrolase Activators
  • GTPase-Activating Proteins
  • Recombinant Proteins
  • Capreomycin
  • Streptomycin