Transcript Profiling of Nitroxoline-Treated Biofilms Shows Rapid Up-regulation of Iron Acquisition Gene Clusters.

Bacterial biofilms are surface-attached communities of slow- or non-replicating cells embedded within a protective matrix of biomolecules. Unlike free-floating planktonic bacteria, biofilms are innately tolerant to conventional antibiotics and are prevalent in recurring and chronic infections. Nitroxoline, a broad-spectrum biofilm-eradicating agent, was used to probe biofilm viability.

An ether-linked halogenated phenazine-quinone prodrug model for antibacterial applications.

Antibiotic-resistant infections present significant challenges to patients. As a result, there is considerable need for new antibacterial therapies that eradicate pathogenic bacteria through non-conventional mechanisms. Our group has identified a series of halogenated phenazine (HP) agents that induce rapid iron starvation that leads to potent killing of methicillin-resistant Staphylococcus aureus biofilms.

Design, synthesis and biological evaluation of a halogenated phenazine-erythromycin conjugate prodrug for antibacterial applications.

There is a significant need for new antibacterial agents as pathogenic bacteria continue to threaten human health through the acquisition of resistance and tolerance towards existing antibiotics. Over the last several years, our group has been developing a novel series of halogenated phenazines that demonstrate potent antibacterial and biofilm eradication activities against critical Gram-positive pathogens, including: Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus faecium. Here, we report the design, chemical synthesis and initial biological assessment of a halogenated phenazine-erythromycin conjugate prodrug 5 aimed at enhancing the translational potential for halogenated phenazines as a treatment of bacterial infections.

Rapid kill assessment of an -arylated NH125 analogue against drug-resistant microorganisms.

While a number of disinfection techniques are employed in healthcare units, the eradication of drug-resistant microorganisms remains a challenge. We recently reported -arylated NH125 analogue , which demonstrated potent biofilm eradication and antibacterial activities against a panel of drug-resistant pathogens. The broad-spectrum activities observed for along with its rapid eradication of MRSA persister cells suggested that this agent, and related analogues, can serve as disinfectants for antibiotic resistant pathogens in healthcare settings.

Eradicating Bacterial Biofilms with Natural Products and Their Inspired Analogues that Operate Through Unique Mechanisms.

Bacterial biofilms are surface-attached communities of slow- or non-replicating bacterial cells that display high levels of tolerance toward conventional antibiotic therapies. It is important to know that our entire arsenal of conventional antibiotics originated from screens used to identify inhibitors of bacterial growth, so it should be little surprise that our arsenal of growth-inhibiting agents have little effect on persistent biofilms. Despite this current state, a diverse collection of natural products and their related or inspired synthetic analogues are emerging that have the ability to kill persistent bacterial biofilms and persister cells in stationary cultures.

Microwave-enhanced Friedländer synthesis for the rapid assembly of halogenated quinolines with antibacterial and biofilm eradication activities against drug resistant and tolerant bacteria.

Herein, we disclose the development of a catalyst- and protecting-group-free microwave-enhanced Friedländer synthesis which permits the single-step, convergent assembly of diverse 8-hydroxyquinolines with greatly improved reaction yields over traditional oil bath heating (increased from 34% to 72%). This rapid synthesis permitted the discovery of novel biofilm-eradicating halogenated quinolines (MBECs = 1.0-23.

Inhibition and dispersion of proteobacterial biofilms.

A small molecule derived from a marine natural product with the ability to inhibit biofilm formation and also disperse established proteobacterial biofilms is presented.