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

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.

• Authors: Shinichi Miyairi, Kazuhiro Tateda, Etsu T Fuse, Chihiro Ueda, Hiroaki Saito, Tohru Takabatake, Yoshikazu Ishii, Manabu Horikawa, Masaji Ishiguro, Theodore J Standiford, Keizo Yamaguchi
• Journal: Journal of medical microbiology (J Med Microbiol) Vol. 55 Issue Pt 10 Pg. 1381-1387 (Oct 2006) ISSN: 0022-2615 [Print] England
• PMID: 17005787 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

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