Targeting Type IV Secretion System Proteins to Combat Multidrug-Resistant Gram-positive Pathogens

J Infect Dis. 2017 Jun 15;215(12):1836-1845. doi: 10.1093/infdis/jix227.

Abstract

For many gram-positive pathogens, conjugative plasmid transfer is an important means of spreading antibiotic resistance . Therefore, the search for alternative treatments to fight and prevent infections caused by these bacteria has become of major interest. In the present study, we evaluated the protein TraM, from the conjugative plasmid pIP501, as a potential vaccine candidate. Anti-TraM antiserum mediated in vitro opsonophagocytic killing of the strain harboring the pIP501 plasmid and also proved to be cross-reactive against other clinically relevant enterococcal and staphylococcal strains. Specificity of antibodies toward TraM was confirmed by results of an opsonophagocytic inhibition assay and Western blot. In addition, conjugative transfer experiments proved that TraM is essential for the transfer of pIP501. Finally, immunization with either TraM or anti-TraM antiserum reduced significantly the colony counts in mice livers, demonstrating that TraM is a promising vaccine candidate against enterococci and other gram-positive pathogens.

Keywords: accine; conjugative transfer; gram-positive pathogens; mouse sepsis model; type IV secretion system (T4SS).

MeSH terms

  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Proteins / immunology*
  • Bacterial Vaccines / immunology*
  • Blotting, Western
  • Drug Resistance, Multiple, Bacterial / immunology*
  • Enterococcus faecalis / genetics
  • Enterococcus faecalis / immunology*
  • Escherichia coli / genetics
  • Escherichia coli / immunology*
  • Female
  • Liver / microbiology
  • Mice
  • Mice, Inbred BALB C
  • Plasmids
  • Protein Transport
  • Rabbits
  • Staphylococcus aureus / immunology
  • Type IV Secretion Systems / immunology*

Substances

  • Bacterial Proteins
  • Bacterial Vaccines
  • Type IV Secretion Systems
  • TraM protein, bacterial