Utilization of microbial iron assimilation processes for the development of new antibiotics and inspiration for the design of new anticancer agents.

Pathogenic microbes rapidly develop resistance to antibiotics. To keep ahead in the "microbial war", extensive interdisciplinary research is needed. A primary cause of drug resistance is the overuse of antibiotics that can result in alteration of microbial permeability, alteration of drug target binding sites, induction of enzymes that destroy antibiotics (ie., beta-lactamase) and even induction of efflux mechanisms. A combination of chemical syntheses, microbiological and biochemical studies demonstrate that the known critical dependence of iron assimilation by microbes for growth and virulence can be exploited for the development of new approaches to antibiotic therapy. Iron recognition and active transport relies on the biosyntheses and use of microbe-selective iron-chelating compounds called siderophores. Our studies, and those of others, demonstrate that siderophores and analogs can be used for iron transport-mediated drug delivery ("Trojan Horse" antibiotics) and induction of iron limitation/starvation (Development of new agents to block iron assimilation). Recent extensions of the use of siderophores for the development of novel potent and selective anticancer agents are also described.

Exposure to a diet high in fat attenuates dendritic spine density in the medial prefrontal cortex.

A key factor in the development of obesity is the overconsumption of food calorically high in fat. Overconsumption of food high in fat not only promotes weight gain but elicits changes in reward processing. No studies to date have examined whether consumption of a high-fat (HF) diet alters structural plasticity in brain areas critical for reward processing, which may account for persistent changes in behavior and psychological function by reorganizing synaptic connectivity. To test whether dietary fat may induce structural plasticity we placed rats on one of three dietary conditions: ad libitum standard chow (SC), ad libitum 60 % HF (HF-AL), or calorically matched 60 % HF (HF-CM) for 3 weeks and then quantified dendritic spine density and type on basal and apical dendrites of pyramidal cells in layer V of the medial prefrontal cortex (mPFC) and medium spiny neurons (MSNs) of the nucleus accumbens. Our results demonstrate a significant reduction in the density of thin spines on the apical and basal segments of dendrites within the infralimbic, but not prelimbic, mPFC.