These statistics underscore the urgent need for novel anti-infectives effective against S. In fact, the number of yearly deaths from MRSA infection has surpassed that of AIDS. The CDC estimates that in 2011, MRSA was responsible for 80,461 life-threatening infections in the United States alone. aureus strains resistant to β-lactam antibiotics such as methicillin (MRSA) present challenges in the treatment of staphylococcal infections. Staphylococci possess a wide spectrum of virulence factors and have developed many strategies to bypass host defense mechanisms. Staphylococcus aureus is a human commensal that is a leading cause of hospital and community-acquired infections, , including bacteremia and sepsis. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.įunding: This study was supported by National Institutes of Health grant P01 AI083214 to EM and FA and grant U54 AI057159 to NERCE. Received: OctoAccepted: JanuPublished: February 19, 2014Ĭopyright: © 2014 Rajamuthiah et al. Kaufmann, The Scripps Research Institute and Sorrento Therapeutics, Inc., United States of America (2014) Whole Animal Automated Platform for Drug Discovery against Multi-Drug Resistant Staphylococcus aureus. aureus assay described here allows screening for anti-staphylococcal compounds that are not toxic to the host.Ĭitation: Rajamuthiah R, Fuchs BB, Jayamani E, Kim Y, Larkins-Ford J, Conery A, et al. aureus isolates and other Gram-positive bacteria. ![]() In further studies, we confirmed the anti-staphylococcal activity of closantel against vancomycin-resistant S. Surprisingly, the antihelminthic drug closantel was also identified as a hit in the screen. elegans survival and were identified as hits in the screen. As proof of principle, 27 of the 30 clinically used antibiotics present in the library conferred increased C. This robust assay with a Z’-factor consistently greater than 0.5 was utilized to screen the Biomol 4 compound library consisting of 640 small molecules with well characterized bioactivities. In validation of the liquid assay, an MRSA cell wall defective mutant, MW2Δ tarO, which is attenuated for killing in the agar-based assay, was found to be less virulent in the liquid assay. aureus (MRSA) and worms in 384-well assay plates, followed by automated microscopy and image analysis. We have developed a high throughput liquid screening assay that uses robotic instrumentation to dispense a precise amount of methicillin resistant S. ![]() However, agar-based assays are not amenable to large scale screens for antibacterial compounds. aureus infection model was previously carried out on solid agar plates where the bacteriovorous C. Staphylococcus aureus, the leading cause of hospital-acquired infections in the United States, is also pathogenic to the model nematode Caenorhabditis elegans.
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