Streptococcus pneumoniae is a pathogen normally found in nasopharynx of about 5-10 % of healthy people. Despite its name, it can cause many other diseases as meningitis, septic meningitis, otitis media, & osteomyelitis.
S. pneumoniae main virulence factors are:
a) Polysaccharide capsule: that inhibits phagocytosis.
b) Pneumolysin: a protein that causes lysis of host cells & activate complement.
c) Hydrogen peroxide: causes damage to host cells.
Researchers led by Jesús M. Sanz at the Miguel Hernandez University and Maarten Merkx at the Eindhoven University of Technology have now introduced a highly promising new approach for the development of drugs to treat pneumococci.
The cell wall of pneumococci contains special polymers, called teichoic acids that are rich in choline which act as a docking station for a number of special proteins that are involved in important processes as:
1) Cell wall division.
2) Release of bacterial toxins.
3) Adhesion to infected tissues.
If choline is added to a culture of pneumococci, the molecules occupy the choline binding sites of the CBPs so that the proteins can no longer bind to the cell walls of the pneumococci.
The bacteria continue to multiply but they can’t separate from each other, these results in long chains of linked cells. Also, the toxin released is stopped.
However, choline is not suitable to be used as a drug because an effective dose would be far too high.
The researchers thus developed the foundation for a new drug that binds CBP much more strongly than individual choline molecules. The drug imitates the choline architecture of the cell wall by presenting multiple choline groups. This will occupy multiple choline binding sites of the CBP.
Also, the required dosage of this CBP inhibitor lies within the range that is acceptable for pharmaceuticals.
Source: Science Daily.
Image credits: S.pneumoniae.
Image credits: S.pneumoniae.Tags: CBPs, choline binding sites, meningitis, osteomyelitis, otitis media, pili, Pneumolysin, Streptococcus pneumoniae, teichoic acids, TNF