New antibiotics for methicillin-resistant Staphylococcus aureus (MRSA) and other pesky bacteria. Andrei Osterman and collaborators have used comparisons of bacterial genomes to identify new targets for antibiotics and produced first-generation chemical inhibitors of a class of bacterial enzymes, called NadDs (nicotinate mononucleotide adenylyltransferases). Described in a recent article in Chemistry & Biology (Cell Press), the team, led by Dr. Osterman, has provided proof of concept for a novel class of antibiotics that could address the problem of antibiotic resistance in MRSA and other types of drug resistant bacteria. It is estimated that within the next one to two decades most antibiotics currently available will be useless due to the emergence of drug resistant strains.
Medical device for juvenile diabetes reaches key milestone on path to clinic. Patients currently receiving islet transplantation therapy for diabetes must undergo lifelong immunosuppression, rendering them more prone to infections and cancer. The idea of encapsulating the insulin-producing cells to hide them from the immune system has been popular for some years, but it has not been applied with much success. Recently Dr. Pamela Itkin-Ansari's team demonstrated that an encapsulation device protected cells from both allograft and autoimmune rejection in rodents, thus allowing this encapsulation therapy to successfully treat diabetes in the absence of immunosuppression. There are, however, differences between rodent and human immune systems. Therefore, as an important step toward clinical trials, Dr. Itkin-Ansari and colleagues have established that the device also provides immunoprotection in primates in an article recently published in Transplantation. With positive data in primates, the next step will be human clinical trials for juvenile diabetes.
Oxidants help cancers metastasize. Dr. Sara A. Courtneidge and colleagues have discovered that reactive oxygen species, such as superoxide and hydrogen peroxide, play a key role in forming invadopodia, cellular protrusions found on metastatic cancer cells. Invadopodia facilitate cancer cell migration by breaking down the extracellular matrix that normally keeps cells in place. In previous research, Dr. Courtneidge discovered that proteins called Tks4 and Tks5 are crucial for invadopodia formation. Now the Courtneidge laboratory has shown that antioxidants caused a marked reduction in invadopodia formation and invasive behavior. The findings also implicated enzymes called NADPH oxidases in the production of reactive oxygen. In collaborative studies with Dr. Gary Bokoch of The Scripps Research Institute, the Courtneidge laboratory has also found that Tks4 and Tks5 are part of a complex of proteins that allow the NADPH oxidases to function. With the discovery of reactive oxygen's role in invadopodia formation, researchers have additional possibilities for drug intervention. Future research and drug development will focus on inhibiting NADPH oxidase activity and limiting invadopodia formation to prevent cancer cell migration. These studies were published in September in the journal Science Signaling.
Complex sugar molecules (glycans) act as tumor suppressors. A team led by Dr. Minoru Fukuda discovered that specialized complex sugar molecules (glycans) that anchor cells in place act as tumor suppressors in breast and prostate cancers. These glycans play a critical role in cell adhesion in normal cells, and the Fukuda team found that the decrease or loss of these complex sugar molecules leads to increased cell migration by invasive cancer cells and metastasis. An increase in expression of the enzyme that produces these glycans, β3GnT1, resulted in a significant reduction in tumor activity. The study, which was published in the journal Proceedings of the National Academy of Sciences, provides a new understanding of the role that complex glycans play in cancer and could lead to new directions in the development of therapeutics.