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C-reactive protein: a predominant LPS-binding acute phase protein responsive to Pseudomonas infection

Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore

Zhenxiao Jin

Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore

Sandra S.H. Tan

Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore

Bow Ho

Department of Microbiology, Faculty of Science, National University of Singapore, Singapore

Jeak L. Ding

Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore, dbsdjl{at}nus.edu.sg

As a structural component of the outer membrane of Gram-negative bacteria, endotoxin, also known as lipopolysaccharide (LPS) exhibits strong immunostimulatory properties, rendering it a pivotal role in the pathogenesis of Gram-negative septicaemia. Our attempt to identify LPS-binding proteins from the hemolymph of the horseshoe crab led to the isolation and identification of C-reactive protein (CRP) as the predominant LPS-recognition protein during Pseudomonas infection. CRP is an evolutionarily ancient member of a superfamily of `pentraxins'. It is a major protein in acute phase of infection in humans. Our investigation of CRP response to Pseudomonas aeruginosa unveiled a robust innate immune system in the horseshoe crab, which displays rapid suppression of a dosage of 10⁶ CFU of bacteria in the first hour of infection and effected complete clearance of the pathogen by 3 days. Such a high dose would have been lethal to mice. Full-length CRP cDNA was cloned. Analysis of the untranslated regions suggests their crucial role in post-transcriptional regulation of CRP transcript levels. Northern blot analysis demonstrated an acute up-regulation of CRP by about 60-fold in 6—48 h of Pseudomonas infection. Taken together, our results provide new insights into the importance of CRP as a conserved molecule for pathogen recognition.

Key Words: C-reactive protein • endotoxin • lipopolysaccharide • Pseudomonas aeruginosa • horseshoe crab

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