SAN FRANCISCO -- Realizing that microbes must be subsistingon something while they line mucus membranes, waiting togain entry to the cells they infect, MicroCarb Inc. founderHoward Krivan set out to find what nourishes them and howthey enter cells.
Krivan, chief scientific officer of the Gaithersburg, Md.,company (NASDAQ:CARB), told attendees at theGlycotechnology Conference here this week that mucusfractionation studies showed Salmonella were using the small,acidic compound phosphatidylserine as their sole source ofcarbon and nitrogen.
This same compound is a cellular adhesion receptor forSalmonella and E. Coli, which implies that the germs are "eatingtheir receptors."
Comparing proteins produced by microbes grown in commonculture media with those grown under in-vivo, lipophilicconditions revealed quite different sets of proteins. "Youshouldn't be looking at the cell surface proteins of microbialcells grown in culture if you're in drug development," hewarned.
The difference also suggests that people should reconsiderliposomal packaging of drugs, Krivan said, as well as the choiceof vaccines to protein antigens.
His newly public company is focusing on developing a vaccinefor ear infection, which is the main cause of pediatric doctorvisits and primarily results from infection with Haemophilusinfluenzae, Stroptococcus pneumoniae and/or Branhamellacatarrhalis.
His company has already found the receptor for H. influenzae,the corresponding "adhesin" protein on the microbe thatmediates attachment and colonization, and researchers havebegun preclinical testing of inhibitors.
Adhesin "anchor" proteins of bacteria, yeast, viruses and toxinsare almost uniformly consistent in content and have anextreme propensity to trigger immune reactions, features thatboth bode well for creating vaccines, he said.
Other therapeutic strategies based on these insights intomicrobe lifestyles include the potential of using enzymes thatdegrade the limited range of microbial nutrients in mucus toprovide relief to cystic fibrosis patients, he suggested. Thisdisease causes excessive mucus production and frequent,potentially deadly, lung infections.
-- Nancy Garcia Associate Editor
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