Evolving role of laminin receptors in microbial pathogenesis and therapeutics of CNS infection.
Evaluation of: Orihuela CJ, Mahdavi J, Thornton J et al.: Laminin receptor initiates bacterial contact with the blood brain barrier in experimental meningitis models. J. Clin. Invest. 119(6), 1638-1646 (2009). Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae are the common pathogens causing bacterial meningitis in childhood. Using in vitro and in vivo models of the blood-brain barrier, affinity chromatography, coimmunoprecipitation, retagging and in vivo imaging approaches, Orihuela et al. have demonstrated that the 37/67-kDa laminin receptor (LR) is a common receptor for all three bacteria on the surface of rodent and human brain microvascular endothelial cells. Pneumococcal choline-binding protein A, meningococcal pilus biogenesis protein Q and class 1 porin, and outer membrane protein P2 of H. influenzae have been identified by mutagenesis as the corresponding bacterial LR-binding adhesins. Their studies further suggest that the bacterial adhesins bind to a common adhesion-recognition site, which is present in the carboxyl terminus of LR. Since these bacterial adhesins and other microbial virulence factors bind to the same host receptor at the blood-brain barrier, LR may provide a broad-spectrum therapeutic target for the prevention and treatment of the CNS infection.
Huang
Sheng-He
SH
Department of Pediatrics, University of Southern California, Saban Research Institute of Childrens Hospital Los Angeles, Los Angeles, CA 90027, USA. shhuang@hsc.usc.edu
Jong
Ambrose
A