Repurposing sunscreen as an antibiotic: zinc-activated avobenzone inhibits methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) is a major healthcare concern with associated healthcare costs reaching over ${\$}$1 billion in a single year in the USA. Antibiotic resistance in S. aureus is now observed against last line of defense antibiotics, such as vancomycin, linezolid, and daptomycin.

Pyrazolyl Thioureas and Carbothioamides with an NNSN Motif against MSSA and MRSA.

A novel series of copper-activatable drugs intended for use against methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) were synthesized, characterized, and tested against the MSSA strain Newman and the MRSA Lac strain (a USA300 strain), respectively. These drugs feature an NNSN structural motif, which enables the binding of copper.

A copper-dependent compound restores ampicillin sensitivity in multidrug-resistant Staphylococcus aureus.

Multi-drug resistant Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), has become a worldwide, major health care problem. While initially restricted to clinical settings, drug resistant S.

Differential Susceptibility of and Species to Compound-Enhanced Copper Toxicity.

Rationale: Mycoplasmas represent important etiologic agents of many human diseases. Due to increasing antimicrobial resistance and slow rate of novel discovery, unconventional methods of drug discovery are necessary. Copper ions are utilized in host microbial killing, and bacteria must regulate intracellular Cu concentrations to avoid toxicity.

Pyrazolopyrimidinones, a novel class of copper-dependent bactericidal antibiotics against multi-drug resistant S. aureus.

The treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections poses a therapeutic challenge as even last resort drugs become increasingly ineffective. As the demand for antibiotics with novel modes of action is growing, new approaches are needed to probe a greater spectrum of antimicrobial activities for their potential efficacy against drug-resistant pathogens. The use of copper (Cu) by the innate immune system to mount an antimicrobial response against bacterial invaders has created an opportunity to explore a role for Cu in antimicrobial therapy.

High-throughput screening and Bayesian machine learning for copper-dependent inhibitors of Staphylococcus aureus.

One potential source of new antibacterials is through probing existing chemical libraries for copper-dependent inhibitors (CDIs), i.e., molecules with antibiotic activity only in the presence of copper.

Copper and Antibiotics: Discovery, Modes of Action, and Opportunities for Medicinal Applications.

Copper is a ubiquitous element in the environment as well as living organisms, with its redox capabilities and complexation potential making it indispensable for many cellular functions. However, these same properties can be highly detrimental to prokaryotes and eukaryotes when not properly controlled, damaging many biomolecules including DNA, lipids, and proteins. To restrict free copper concentrations, all bacteria have developed mechanisms of resistance, sequestering and effluxing labile copper to minimize its deleterious effects.

8-Hydroxyquinolines Are Boosting Agents of Copper-Related Toxicity in Mycobacterium tuberculosis.

Copper (Cu) ions are likely the most important immunological metal-related toxin utilized in controlling bacterial infections. Impairment of bacterial Cu resistance reduces viability within the host. Thus, pharmacological enhancement of Cu-mediated antibacterial toxicity may lead to novel strategies in drug discovery and development.

Targeting Biofilm Associated Staphylococcus aureus Using Resazurin Based Drug-susceptibility Assay.

Most pathogenic bacteria are able to form biofilms during infection, but due to the difficulty of manipulating and assessing biofilms, the vast majority of laboratory work is conducted with planktonic cells. Here, we describe a peg plate biofilm assay as performed with Staphylococcus aureus. Bacterial biofilms are grown on pegs attached to a 96-well microtiter plate lid, washed through gentle submersion in buffer, and placed in a drug challenge plate.

Development of a web-based tool for automated processing and cataloging of a unique combinatorial drug screen.

Facing totally resistant bacteria, traditional drug discovery efforts have proven to be of limited use in replenishing our depleted arsenal of therapeutic antibiotics. Recently, the natural anti-bacterial properties of metal ions in synergy with metal-coordinating ligands have shown potential for generating new molecule candidates with potential therapeutic downstream applications. We recently developed a novel combinatorial screening approach to identify compounds with copper-dependent anti-bacterial properties.

Combinatorial phenotypic screen uncovers unrecognized family of extended thiourea inhibitors with copper-dependent anti-staphylococcal activity.

The continuous rise of multi-drug resistant pathogenic bacteria has become a significant challenge for the health care system. In particular, novel drugs to treat infections of methicillin-resistant Staphylococcus aureus strains (MRSA) are needed, but traditional drug discovery campaigns have largely failed to deliver clinically suitable antibiotics. More than simply new drugs, new drug discovery approaches are needed to combat bacterial resistance.

Disulfiram and Copper Ions Kill Mycobacterium tuberculosis in a Synergistic Manner.

Tuberculosis is a severe disease affecting millions worldwide. Unfortunately, treatment strategies are hampered both by the prohibitively long treatment regimen and the rise of drug-resistant strains. Significant effort has been expended in the search for new treatments, but few options have successfully emerged, and new treatment modalities are desperately needed.

Commercially available complement component-depleted sera are unexpectedly codepleted of ficolin-2.

The ficolins are a family of innate pattern recognition molecules that are known to bind acetylated compounds and activate complement through the association of mannose binding lectin (MBL)/ficolin-associated serine proteases (MASPs). Their importance has more recently become appreciated, as they have been shown to play a role in a variety of disease processes from infection to autoimmunity. While studying ficolin-2-mediated complement deposition on Streptococcus pneumoniae, we found that sera depleted of C1q or other complement components were also codepleted of ficolin-2 but not ficolin-1, ficolin-3, or MBL.

An insight into the significance of the DnaK heat shock system in Staphylococcus aureus.

The bacterium Staphylococcus aureus utilizes a variety of different mechanisms to survive unfavorable stress conditions that are critical for its persistence in the environment and for pathogenicity. The staphylococcal DnaK heat shock system functions as a major protein folding machine under stress conditions that cause aggregation and un-folding of proteins. In prior studies, S.