Crumbling the Castle: Targeting DNABII Proteins for Collapsing Bacterial Biofilms as a Therapeutic Approach to Treat Disease and Combat Antimicrobial Resistance.

Antimicrobial resistance (AMR) is a concerning global threat that, if not addressed, could lead to increases in morbidity and mortality, coupled with societal and financial burdens. The emergence of AMR bacteria can be attributed, in part, to the decreased development of new antibiotics, increased misuse and overuse of existing antibiotics, and inadequate treatment options for biofilms formed during bacterial infections. Biofilms are complex microbiomes enshrouded in a self-produced extracellular polymeric substance (EPS) that is a primary defense mechanism of the resident microorganisms against antimicrobial agents and the host immune system.

The effect of the melanocortin agonist, MT-II, on the defended level of body adiposity.

A wide range of experimental evidence implicates a critical role for melanocortin signaling in the control of food intake and body adiposity. Melanocortin receptor agonists such as MT-II potently reduce food intake and body weight, making such agonists potential therapeutics for obesity. The critical concept addressed by the present experiments is whether the homeostatic effects of melanocortin agonists directly regulate food intake or whether the effects on food intake are secondary, with the primary effects being the regulation of body weight and adiposity.

Two novel paradigms for the simultaneous assessment of conditioned taste aversion and food intake effects of anorexic agents.

The conditioned taste aversion (CTA) is routinely used to assess the aversive consequences of anorexic agents, including potential pharmacological therapies for obesity. In a typical CTA paradigm, rats briefly sampling a novel tastant (e.g.

Assessment of the aversive consequences of acute and chronic administration of the melanocortin agonist, MTII.

Background: The synthetic melanocortin (MC) agonist, melanotan-II (MTII), reduces food intake and body weight for hours to days after administration. One early report on the effect of MTII suggested that part of its anorexic action may be mediated by aversive consequences. In that experiment, MTII was found to support a mild conditioned taste aversion (CTA).

Comparison of central and peripheral administration of C75 on food intake, body weight, and conditioned taste aversion.

Mice respond to fatty acid synthase (FAS) inhibitors by profoundly reducing their food intake and body weight. Evidence indicates that the central nervous system (CNS) may be the critical site of action; however, a peripheral contribution cannot be ruled out. We compared doses of the FAS inhibitor C75 in the CNS (third ventricle [i3vt]) and periphery (intraperitoneal [IP]) to reduce food intake and body weight in rats.