A Facile High-Throughput Model of Surface-Independent Staphylococcus aureus Biofilms by Spontaneous Aggregation.

Many microbes in their natural habitats are found in biofilm ecosystems attached to surfaces and not as free-floating (planktonic) organisms. Furthermore, it is estimated that nearly 80% of human infections are associated with biofilms. Biofilms are traditionally defined as three-dimensional, structured microbial communities that are attached to a surface and encased in a matrix of exopolymeric material.

Antimicrobial and Antibiofilm Activity of Synergistic Combinations of a Commercially Available Small Compound Library With Colistin Against .

Biofilm-associated infections remain a significant clinical challenge since the conventional antibiotic treatment or combination therapies are largely ineffective; and new approaches are needed. To circumvent the major challenges associated with discovery of new antimicrobials, we have screened a library of compounds that are commercially available and approved by the FDA (Prestwick Chemical Library) against for effective antimicrobial and anti-biofilm activity. A preliminary screen of the Prestwick Chemical Library alone did not yield any repositionable candidates, but in a screen of combinations with a fixed sub-inhibitory concentration of the antibiotic colistin we observed 10 drugs whose bacterial inhibiting activity was reproducibly enhanced, seven of which were enhanced by more than 50%.

High-throughput microarray for antimicrobial susceptibility testing.

We describe the development of a novel, high-throughput, nano-scale microarray platform for antimicrobial susceptibility testing (AST). The platform allows to process 480 samples at 50 nL volume on a single chip, analyze by fluorescence read-out with an easy dunk-and-rinse step, and the ability to process multiple samples and chips simultaneously. We demonstrate the applicability of this chip for culturing community acquired methicillin resistant (CA-MRSA), and perform AST against clinical isolates of CA-MRSA.

Chip, a Lab-on-a-Chip Platform of Mono- and Polymicrobial Biofilms for High-Throughput Downstream Applications.

Current techniques for the culture of microorganisms, and particularly of delicate microbial biofilms, are still mostly limited to low-density plates and manual labor and are not amenable to automation and true high-throughput (HT) applications. We have developed a novel fully automated platform for the formation of mono- and polymicrobial biofilms of , , and at the nanoscale level. The Chip is robotically printed, robustly handled, and scanned using a standard microarray reader.

Screening a Commercial Library of Pharmacologically Active Small Molecules against Staphylococcus aureus Biofilms.

It is now well established that bacterial infections are often associated with biofilm phenotypes that demonstrate increased resistance to common antimicrobials. Further, due to the collective attrition of new antibiotic development programs by the pharmaceutical industries, drug repurposing is an attractive alternative. In this work, we screened 1,280 existing commercially available drugs in the Prestwick Chemical Library, some with previously unknown antimicrobial activity, against Staphylococcus aureus, one of the commonly encountered causative pathogens of burn and wound infections.