br Concluding Remarks and Future Perspectives Fluorescent an

Concluding Remarks and Future Perspectives Fluorescent NVP-LCQ195 receptor have helped researchers to elucidate antibiotic MOA and off-target interactions, to screen for new antibiotics, to detect antibiotics in the environment, to track antibiotic uptake throughout cells and organisms, and to detect bacterial infections. Despite this broad utility, the number of fluorescent antibiotics available for these studies remains limited and hence these tools have not yet realised their full potential (see Outstanding Questions). Fluorescent versions of all major antibiotic classes should be prepared, in addition to developing more colour variations of existing probes. The ‘best’ fluorophore will depend on the intended use: NIR is needed for in vivo imaging, but BODIPY is much brighter and suitable for confocal microscopy. Critically, the in vitro target-based activity and bacterial MIC of all new conjugates must be tested to confirm that they accurately mimic the parent antibiotic. This toolset of antibiotic-derived probes should be made readily available to antimicrobial resistance researchers, who may well find novel and unanticipated applications that help progress our fight against resistant bacteria. One possible application is to replace the nonspecific fluorescent probes used in multiplexed assays developed for rapid bacteria susceptibility profiling [92] or MOA determination [93]. In particular, the development of additional NIR fluorescent antibiotics could lead to powerful probes for in vivo imaging of bacterial infections in the clinic. However, several challenges must be overcome, including the obstacles of limited tissue penetration for fluorescent signals, and the need for development of appropriate imaging equipment in the hospital. One possible application ripe for exploration that overcomes both of these barriers is the ‘topical’ use of antibacterial fluorophore probes to highlight infected tissue needing removal during surgery, just as ‘tumour paints’ are now being used to visibly distinguish a tumour from normal brain tissue. It is hoped that research into fluorescent antibiotics and their use in biomedical research will continue to grow and contribute to our efforts to fight antibiotic-resistant infections.
Acknowledgements The authors would like to thank Marwa Hassan for figure advice. M.R.L.S. is supported by an Australian Postgraduate Award (APA) PhD scholarship. M.S.B. and M.A.T.B. are supported in part by Wellcome Trust Strategic GrantWT1104797/Z/14/Z. M.A.C. is a NHMRC principle research fellow (APP1059354) and also holds a fractional professorial research fellow appointment at the University of Queensland.
Introduction According to Drake (2011), surgical site infections account for 38% of the total number of infections acquired within the hospital setting. The Centers for Medicare and Medicaid Services and the Centers for Disease Control spearheaded a program in 2002 to focus on the use of prophylactic antibiotics to help address the problem (Drake, 2011). Antibiotic prophylaxis in the surgical environment is targeted at preventing the surgical wound from becoming contaminated or infected by body fluids or organisms contained on the patient's skin (Venkatesan et al., 2010). With advances in interventional devices and imaging technology, interventional radiology (IR) has grown into a practice that allows physicians to use minimally invasive techniques to treat disease processes. As the IR specialty evolved, organizations such as the Society for Interventional Radiology (SIR) adopted many infection-reducing protocols from the surgical specialty (Moon et al., 2010, Ryan et al., 2004, Sutcliffe et al., 2015, Venkatesan et al., 2010). In IR procedures, surgical wounds are tiny; however, infection can arise from the interaction that takes place between the catheter, space being manipulated, and bloodstream (Venkatesan et al., 2010).