Posts Tagged “drug targets”

GBS (purple) invading BBB (red)Many drugs can’t do it, but GBS can!

Bacterial meningitis is one of the leading causes of death and disability among childrens.  Meningits occurs when bacteria cross blood brain barrier  (BBB) after interacting with human Brain microvascular endothelial cells (hBMECs) . Although these cells are exhibiting tight junctions and lacking pinocytosis, some bacteria could cross it and this demonstrates an interplay between host cells and some bacterial factors.

Scientists at USCD school of medicine used a process involving generating and screening of many group B streptococcus (GBS)  in tissue culture model of human BBB (consisting of immortalised hBMECs) . This culture maintained the normal function of human BBB.

 They identified a gene called iagA gene encoding for a glycosyltransferase. A predicted product of the iagA glycosyltransferase is the glycolipid  diglycosyldiacylglycerol involved in anchoring lipoteichoic acid (LTA) and consequently, enhances BBB invasion.

Allelic replacement of the iagA gene,so that the resulting mutants are lacking the gene, shed LTA into the media. As a result, mice infected with mutant gene exhibited less mortality rate -up to 90 percent- compared to wild-type infected mice. Mutant-type infected mice developed bacteremia  as WT which proves the fact that iagA gene plays the central role in BBB invasion without significantly affecting adhesion or blood survival.

Since bacterial meningitis may cause infected children death or many complications as permanent cognitive deficits, blindness, deafness or seizures, an early treatment may help reduce high rates of death and disability.

This early treatment may be much more easily designed after these findings by blocking LTA anchoring on bacterial cell surface.This will help preventing meningitis even though bacteriemia has taken place.

The journal of clinical investigation has the full story.

 

 

Tags: , ,

Comments No Comments »


StatCounter