Abstract
Through the expression of the accessory gene regulator quorum sensing cascade, Staphylococcus aureus is able to produce an extensive array of enzymes, hemolysins and immunomodulators essential to its ability to spread through the host tissues and cause disease. Many have argued for the discovery and development of quorum sensing inhibitors (QSIs) to augment existing antibiotics as adjuvant therapies. Here, we discuss the state-of-the-art tools that can be used to conduct screens for the identification of such QSIs. Examples include fluorescent reporters, MS-detection of autoinducing peptide production, agar plate methods for detection of hemolysins and lipase, High performance liquid chromatography-detection of hemolysins from supernatants, and cell-toxicity assays for detecting damage (or relief thereof) against human keratinocyte cells. In addition to providing a description of these various approaches, we also discuss their amenability to low-, medium-, and high-throughput screening efforts for the identification of novel QSIs.
Highlights
Staphylococcus aureus is an opportunistic pathogen that is the causative agent of numerous acute and chronic infections (Skov et al, 2012; Uhlemann et al, 2014)
We aim to review the various tools being used in these ongoing efforts to identify novel inhibitors of the S. aureus agr system
THE quorum sensing inhibitors (QSIs) DETECTOR TOOLBOX Following a review of the literature on the staphylococcal agr system, we have identified four major groups of in vitro and ex vivo tools used for assessing agr function: agar plate assays, cell culture and ex vivo techniques, chromatographic tools and molecular tools
Summary
Staphylococcus aureus is an opportunistic pathogen that is the causative agent of numerous acute and chronic infections (Skov et al, 2012; Uhlemann et al, 2014). The hypervirulent nature of CA-MRSA is due to its active cell– cell communication pathway, or quorum sensing system, which controls expression of an extensive array of enzymes, hemolysins, and immunomodulators that are essential to its ability to spread through tissues and cause disease (Novick, 2003) These virulence factors serve a wide scope of purposes in the infection process, including disruption of the epithelial barrier, inhibition of opsonization by antibody and complement, neutrophil cytolysis, interference with neutrophil chemotaxis, and inactivation of antimicrobial peptides (Tsuji et al, 2007; Spaan et al, 2013; Foster et al, 2014; Otto, 2014).
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
