Previous research has found that the musical intervals found in speech are associated with various emotions. Intervals can be classified by their level of consonance or dissonance—how pleasant or unpleasant the combined tones sound to the ear. Exploratory investigations have indicated that in an agreeable conversation, the pitches of the last word in an utterance and the first word of a conversation partner’s utterance are consonantly related; in a disagreeable conversation, the two pitches are dissonantly related. The present results showed that the intervals between the tonics of the utterances in a conversation corresponded to the agreement between interlocutors.
The widespread of use of antibiotics to treat bacterial infection has selected for antibiotic resistant strains of bacteria. Fosfomycin is an example of a broad spectrum antibiotic that has become less effective because of increased bacterial resistance. Fosfomycin inhibits synthesis of peptidoglycan, a structural component of the bacterial cell wall. Fosfomycin covalently binds to the phosphoenolpyruvate binding site of the enzyme MurA, an essential enzyme in the peptidoglycan synthesis pathway. MurA catalyzes the addition of the enolpyruvate to UDP‐N‐acetylglucosamine. The additional product, an inorganic phosphate, is detected by the indicator, malachite green. Muzyka, et al. has identified putative inhibitors through DOCK and AMBER studies. IC50 values have been determined for BCB33b and VS5 of these molecules. Additional molecules with similar functional groups are being synthesized and evaluated as putative inhibitors. The site of inhibitor binding will be determined with in silico studies and site‐directed mutagenesis.
Grant Funding Source: Centre College Faculty Development Fund and the Alcock Interdisciplinary Fund
Antibiotic resistance necessitates the continuous development of novel inhibitors targeting a variety of bacterial pathways. The pathway for the synthesis of peptidoglycan, a necessary component of the bacterial cell wall, is an ideal target for antibiotic development for two reasons: 1) the cell wall is a prokaryote‐specific structure, and 2) the cell wall is necessary for bacterial survival. MurA, the target of current study, is the enzyme that catalyzes the first step in peptidoglycan biosynthesis. Our objective is to develop novel inhibitors that competitively bind to the MurA catalytic sight for UDP‐N‐acetylglucosamine. In an effort to study the effects of various putative inhibitors on MurA, the active enzyme was purified in high concentrations. In vitro tests of the known inhibitor fosfomycin and other potential inhibitors were conducted using the purified enzyme. The Malachite green assay as previously described was used to determine the IC50 values for a number of potential inhibitors. Of the compounds assayed, two salts, VS5 and BCB33b, exhibited consistent IC50 values of 160 uM and 300 uM respectively. The IC50 values of the two putative inhibitors are the lowest we have seen out of all the tested compounds; therefore, VS5 and BCB33b will be tested further in vitro, in vivo, and in silico in their salt and acid forms for comparison against the known inhibitor fosfomycin.
Grant Funding Source: Faculty Development Committee, Centre College
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