The devastating impact of Super Storm Sandy on the NYU Medical center was caused by the total flooding of the lower levels of the entire Medical Center, including the Smilow Vivarium, which was under 15 of water. This caused not only the loss of electric power, air circulation, running water, etc., but also the destruction of our IVIS imaging camera and the loss of all of our mice, 30 of which were at that time being used for an experiment on the effect of the AIP on kidney infections following the IV inoculation of virulent staphylococci. We had been using bacteria tagged with a luciferase reporter to monitor the fate of the infecting bacteria by imaging in the IVIS. Although our luciferase reporters worked well for the subcutaneous infection model, we found, during a subsequent experiment that our luciferase constructs did not provide a sufficiently strong signal for the detection of bacteria in the kidney abscesses which develop following IV inoculation of staphylococci and so we had to use other parameters, such as weight loss, morbidity, and mortality to evaluate the results. Consequently, we spent a considerable amount of time developing new reporters with higher luciferase activities or with fluorescent proteins (E2- crimson and iRFP) that are excited and emit in the near infra-red. The newer luciferase constructs were being used in the experiment that was in progress at the time of the storm. Since these strains were still being tested, they were stored temporarily on plates in the cold room and in a -20 freezer. Among the consequences of the storm, described in more detail in the accompanying application for a for-cost extension of our other grant, R01-AI22159, were the loss of power for these freezers and the cold room, resulting in the loss of all these temporary cultures, and in our entire supply of AIPs, which were stored in solution in a +4 refrigerator, whose temperature reached 50C during the power outage, causing hydrolysis of the thiolactone bond essential for AIP activity.
Staphylococcus aureus; long a scourge of the hospital; has invaded the outside community with enhanced virulence and high contagion. Our project is aimed at understanding the pathobiology of the organism and learning how to block its ability to cause disease by interfering with the function of a key bacterial signaling system that activates the production of toxins and other detrimental substances.
|Wang, Boyuan; Zhao, Aishan; Novick, Richard P et al. (2014) Activation and inhibition of the receptor histidine kinase AgrC occurs through opposite helical transduction motions. Mol Cell 53:929-40|
|George Cisar, Elizabeth A; Geisinger, Edward; Muir, Tom W et al. (2009) Symmetric signalling within asymmetric dimers of the Staphylococcus aureus receptor histidine kinase AgrC. Mol Microbiol 74:44-57|
|Geisinger, Edward; Muir, Tom W; Novick, Richard P (2009) agr receptor mutants reveal distinct modes of inhibition by staphylococcal autoinducing peptides. Proc Natl Acad Sci U S A 106:1216-21|
|Geisinger, Edward; George, Elizabeth A; Muir, Tom W et al. (2008) Identification of ligand specificity determinants in AgrC, the Staphylococcus aureus quorum-sensing receptor. J Biol Chem 283:8930-8|
|George, Elizabeth A; Novick, Richard P; Muir, Tom W (2008) Cyclic peptide inhibitors of staphylococcal virulence prepared by Fmoc-based thiolactone peptide synthesis. J Am Chem Soc 130:4914-24|
|George, Elizabeth A; Muir, Tom W (2007) Molecular mechanisms of agr quorum sensing in virulent staphylococci. Chembiochem 8:847-55|
|Ji, Guangyong; Pei, Wuhong; Zhang, Linsheng et al. (2005) Staphylococcus intermedius produces a functional agr autoinducing peptide containing a cyclic lactone. J Bacteriol 187:3139-50|
|Adhikari, Rajan P; Novick, Richard P (2005) Subinhibitory cerulenin inhibits staphylococcal exoprotein production by blocking transcription rather than by blocking secretion. Microbiology 151:3059-69|
|Lyon, Gholson J; Muir, Tom W (2003) Chemical signaling among bacteria and its inhibition. Chem Biol 10:1007-21|
|Lyon, Gholson J; Wright, Jesse S; Muir, Tom W et al. (2002) Key determinants of receptor activation in the agr autoinducing peptides of Staphylococcus aureus. Biochemistry 41:10095-104|
Showing the most recent 10 out of 12 publications