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Volume 55, Issue 10

Immunization with 3-oxododecanoyl--homoserine lactone–protein conjugate protects mice from lethal lung infection Free

Abstract

Quorum-sensing systems have been reported to play a critical role in the pathogenesis of several bacterial infections. Recent data have demonstrated that -3-oxododecanoyl--homoserine lactone (3-oxo-C-homoserine lactone, 3-oxo-C-HSL), but not -butanoyl--homoserine lactone (C-HSL), induces apoptosis in macrophages and neutrophils. In the present study, the effects of active immunization with 3-oxo-C-HSL–carrier protein conjugate on acute lung infection in mice were investigated. Immunization with 3-oxo-C-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 3×10 c.f.u. 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 (<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)- in the immunized mice were significantly lower than those of control mice (<0.05). Furthermore, the extractable 3-oxo-C-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-C-HSL-mediated apoptosis in macrophages . These results demonstrated that specific antibody to 3-oxo-C-HSL plays a protective role in acute 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.

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Keyword(s): 3-oxo-C12-HSL, N-3-oxododecanoyl-l-homoserine lactone , C4-HSL, N-butanoyl-l-homoserine lactone , HRP, horseradish peroxidase , HSL, homoserine lactone , IL, interleukin , OV, ovalbumin and TNF, tumour necrosis factor
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2006-10-01
2024-04-19
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Immunization with 3-oxododecanoyl-l-homoserine lactone–protein conjugate protects mice from lethal Pseudomonas aeruginosa lung infection
J. Med. Microbiol. 55, 1381 (2006); https://doi.org/10.1099/jmm.0.46658-0
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