Immunization with 3-oxododecanoyl-L-homoserine lactone-protein conjugate protects mice from lethal Pseudomonas aeruginosa lung infection

J Med Microbiol. 2006 Oct;55(Pt 10):1381-1387. doi: 10.1099/jmm.0.46658-0.

Abstract

Quorum-sensing systems have been reported to play a critical role in the pathogenesis of several bacterial infections. Recent data have demonstrated that Pseudomonas N-3-oxododecanoyl-L-homoserine lactone (3-oxo-C12-homoserine lactone, 3-oxo-C12-HSL), but not N-butanoyl-L-homoserine lactone (C4-HSL), induces apoptosis in macrophages and neutrophils. In the present study, the effects of active immunization with 3-oxo-C12-HSL-carrier protein conjugate on acute P. aeruginosa lung infection in mice were investigated. Immunization with 3-oxo-C12-HSL-BSA conjugate (subcutaneous, four times, at 2-week intervals) elaborated significant amounts of specific antibody in serum. Control and immunized mice were intranasally challenged with approximately 3 x 10(6) c.f.u. P. aeruginosa PAO1, and survival was then compared. All control mice died by day 2 post bacterial challenge, while 36 % of immunized mice survived to day 4 (P<0.05). Interestingly, bacterial numbers in the lungs did not differ between control and immunized groups, whereas the levels of pulmonary tumour necrosis factor (TNF)-alpha in the immunized mice were significantly lower than those of control mice (P<0.05). Furthermore, the extractable 3-oxo-C12-HSL levels in serum and lung homogenate were also significantly diminished in the immunized mice. Immune serum completely rescued reduction of cell viability by 3-oxo-C12-HSL-mediated apoptosis in macrophages in vitro. These results demonstrated that specific antibody to 3-oxo-C12-HSL plays a protective role in acute P. aeruginosa infection, probably through blocking of host inflammatory responses, without altering lung bacterial burden. The present data identify a promising potential vaccine strategy targeting bacterial quorum-sensing molecules, including autoinducers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Butyrolactone / administration & dosage
  • 4-Butyrolactone / analogs & derivatives*
  • 4-Butyrolactone / analysis
  • 4-Butyrolactone / immunology
  • Animals
  • Antibodies, Bacterial / blood
  • Antibodies, Bacterial / pharmacology
  • Apoptosis / drug effects
  • Cell Line
  • Colony Count, Microbial
  • Homoserine / administration & dosage
  • Homoserine / analogs & derivatives*
  • Homoserine / analysis
  • Homoserine / immunology
  • Immune Sera / pharmacology
  • Injections, Subcutaneous
  • Lung / metabolism
  • Lung / microbiology
  • Macrophages / drug effects
  • Macrophages / pathology
  • Mice
  • Mice, Inbred BALB C
  • Pneumonia, Bacterial / blood
  • Pneumonia, Bacterial / metabolism
  • Pneumonia, Bacterial / prevention & control*
  • Pseudomonas Infections / blood
  • Pseudomonas Infections / metabolism
  • Pseudomonas Infections / prevention & control*
  • Pseudomonas aeruginosa* / immunology
  • Pseudomonas aeruginosa* / isolation & purification
  • Serum Albumin, Bovine / administration & dosage*
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / metabolism
  • Vaccination*
  • Vaccines, Conjugate / administration & dosage
  • Vaccines, Synthetic

Substances

  • Antibodies, Bacterial
  • Immune Sera
  • N-(3-oxododecanoyl)homoserine lactone
  • Tumor Necrosis Factor-alpha
  • Vaccines, Conjugate
  • Vaccines, Synthetic
  • homoserine lactone
  • Serum Albumin, Bovine
  • Homoserine
  • 4-Butyrolactone