Bacteria have specific surface proteins which are used for binding to host cells. Scientists at the Centre of Advanced Study in Crystallography and Biophysics, at the University of Madras, have succeeded in characterising such surface proteins of some pathogenic bacteria including Streptococcus agalactiae and Enterococcus faecium. Infection by both of these bacteria can have deadly effects on humans.
The studies by the group have also shown that the structure of the surface protein of E. faecium has a special fold which sets it apart from all known categories of protein structure known so far. These results have been published in journals Royal Society of Chemistry Advances and Federation of European Biochemical Society Journal, respectively. The findings can be used to develop drugs to target bacteria that are resistant to treatment with antibiotics.
Lock and key
In order to colonise a host cell, bacteria need to attach themselves to the surface of the host using certain surface proteins.
The surface protein on the bacterial cell functions as a “key” to the protein on the host cell membrane which acts as a “lock” — that is to say, the former fits snugly into the latter. This linking up by means of the lock and key mechanism is crucial for the infection to proceed. Therefore, drugs may be developed to hinder this process of formation of the link. The crucial thing to know in this case is the structure of the surface proteins of the bacteria, which is what the group works at.
The strain S. agalacticae is a Gram positive bacterium that causes life-threatening diseases such as bacterial sepsis and meningitis in newborn babies and several diseases including pneumonia in non-pregnant adults. The group has characterised the structure and binding properties of its surface proteins.
But the more exciting discovery is the structure of the SgrA protein of E. faecium. This antibiotic-resistant bacterium causes urinary tract infection and surgical site infections. Catheter-induced infections could also be caused by this strain as its surface protein SgrA is known to be able to bind to abiotic surfaces, such as polystyrene.
“In E. faecium we determined the crystal structure of surface protein SgrA. This protein is one of those critical for bacterial colonisation and biofilm formation on inserted medical devices,” says Prof. Karthe Ponnuraj, who is head of the department and a coauthor.
X-ray diffraction
The process involved first cloning and purifying the protein and crystallising it. The structure was discovered by X-ray diffraction. “We had to go to Italy multiple times to do this as the facility is not available in India. The third time we were able to get the crystal structure,” says Prof. Karthe, referring to the Elettra Sincrotrone facility at Trieste in Italy.
To their surprise the team discovered that the structure of SgrA contained a fold that did not fit into the known catalogues of protein structures in the Protein Structure Database.
The discovery can be used by drug developers to target these unique surface adhesins and thereby tackle, among others, catheter-related infections.
