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Polyphosphoinositides suppress the adhesion of Haemophilus influenzae to pharyngeal cells

Jim-Wen R Liu1* email, Steve N Anderson2* email, Jonathan A Meulbroek2* email, Shie-Ming Hwang1 email, Pradip Mukerji1 email and Yung-Sheng Huang1* email

Ross Products Division, Abbott Laboratories, 625 Cleveland Ave., Columbus, OH 43216, USA

Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Chicago, IL 60064-6110, USA

author email corresponding author email* Contributed equally

Lipids in Health and Disease 2004, 3:20doi:10.1186/1476-511X-3-20

Published: 3 September 2004

Abstract

Background

One of the primary causes of otitis media (OM), an inflammation of the middle ear, is the bacterium Haemophilus influenzae (HI). OM often occurs to young children, and is mostly treated with antibiotics. Due to concerns over bacterial resistance toward antibiotics, reliable prophylactic treatments such as administrating anti-adhesion agents are now viewed as viable alternatives.

Results

The present study tested the feasibilty of using phosphoinositides as anti-adhesion agents against HI cells. Cells of non-typeable HI were radiolabeled with 111- indium-oxine, pre-incubated with various individual phosphoinositides for 15 minutes at 37°C, and incubated with a monolayer of human pharynx carcinoma (DT 562) cells for 20 minutes at 37°C. The result showed that at 0.1 mg/mL dipalmitoylphosphatidylinositol-3,4-diphosphate (PI-3,4-PP) had the highest anti-adhesion activity, followed by phosphatidylinositol-3-phosphate (PI-3-P) and phosphatidylinositol-4-phosphate (PI-4-P). The anti-adhesion activity of PI-3,4-PP was dose-dependent ranging from 0.006 to 0.1 mg/mL. In addition, results from an in vivo study demonstrated that pre-incubation of HI cells with PI-3,4-PP at 1 mg/mL suppressed the growth of HI in nasopharynx of neonatal rats.

Conclusions

These findings suggest that PI-3-P and PI-4-P and more so PI-3,4-PP may serve as prophylactic agents against HI adhesion and colonization.


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