Scientists discover how a bacterial pathogen breaks down barriers to enter and infect cells
“We are excited about this finding,” says Ilene Gipson, Ph.D., the study’s principal investigator and a senior scientist at the Schepens. “Our discovery may ultimately lead to new ways of diagnosing, treating and preventing bacterial infections originating not only in the eye but in other parts of the body as well.”
More than 80 percent of infections are contracted through the body’s mucus membranes, which are the wet epithelial surfaces of the eye and the urogenital, respiratory, and gastrointestinal tracts of the body. The outer surface of all mucus membranes are protected by two types of mucin molecules – one that is secreted and is in constant motion to sweep away trapped foreign material from the membrane surface, and the other that remains rooted in the membrane surface. The latter type of mucin molecules constitutes a physical shield that keeps potentially harmful substances from penetrating the membrane.
To test their hypothesis, the team grew “epidemic” conjunctivitis bacteria (a strain of Streptococcus pneumoniae) in a culture. This bacteria causes an inflammation of the conjunctiva, the mucous membrane covering the white of the eyes and the inner side of the eyelids.
They then applied the fluid that the bacteria were cultured in to cell lines that mimicked the eye’s surface, including presence of intact mucins, and found that the membrane-anchored mucins were cut off and released from the surface of the cells. Removal of the mucins allowed the bacteria to enter the cells.
Using mass spectrometry, the researchers were then able to identify the enzyme, ZmpC, as the culprit. They confirmed their findings by knocking out the gene in the bacteria that produced this enzyme and demonstrated that the bacterium could no longer remove the mucins from the membrane.
According to Dr. Gipson, “This discovery is a major breakthrough in this long unsolved puzzle about how “epidemic” bacteria enter the body and has given us a new target for drugs that could even be used preventatively.”