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The World Health Organization considers the discovery of new treatments for P. aeruginosa a top priority. Virulence attenuating combination therapy (VACT) is a pragmatic strategy to improve bacterial clearance, repurpose outmoded antibiotics, improve drug efficacy at lower doses, and reduce the evolution of resistance. In vitro and in vivo studies have shown that adding a quorum sensing inhibitor or an extracellular polymeric substance repressor to classical antibiotics synergistically improves antipseudomonal activity. This review highlights why VACT could specifically benefit cystic fibrosis patients harboring chronic P. aeruginosa infections, outlines the current landscape of synergistic combinations between virulence-targeting small-molecules and anti-pseudomonal drugs, and suggests future directions for VACT research.more » « less
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The prevalence of biofilm diseases, and dental caries in particular, have encouraged extensive research on S. mutans biofilms, including methods of preventing its formation. Numerous small molecules with specific anti-biofilm activity against this pathogen have been isolated and synthesized. Generally, these molecules can be characterized into three categories: sucrose-dependent anti-adhesion, sucrose-independent anti-adhesion and cellular signaling interference. This review aims to provide an overview of the current small molecule strategies used for targeting S. mutans biofilms, and a perspective of the future for the field.more » « less
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The rise of antibiotic resistant bacteria has become a problem of global concern. Of particular interest are the ESKAPE pathogens, species with high rates of multi-drug resistant infections. Novel antibiotic mechanisms of action are necessary to compliment traditional therapeutics. Recent research has focused on targeting virulence factors as a method of combatting infection without creating selective pressure for resistance or damaging the host commensal microbiome. Some investigations into one such virulence behavior, iron acquisition, have displayed additional effects on another virulence behavior, biofilm formation. The use of exogenous iron-chelators, gallium as an iron mimic, and inhibition of siderophore-mediated iron acquisition are all strategies for disturbing iron-homeostasis that have implicated effects on biofilms. However, the exact nature of this connection remains ambiguous. Herein we summarize these findings and identify opportunities for further investigation.more » « less
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