Evaluation of bacteriophage as an adjunct therapy for treatment of peri-prosthetic joint infection caused by Staphylococcus aureus

Phage therapy offers a potential alternate strategy for the treatment of peri-prosthetic joint infection (PJI), particularly where limited effective antibiotics are available. We undertook preclinical trials to investigate the therapeutic efficacy of a phage cocktail, alone and in combination with vancomycin, to reduce bacterial numbers within the infected joint using a clinically-relevant model of Staphylococcus aureus-induced PJI. Infected animals were randomised to 4 treatment groups, with treatment commencing 21-days post-surgery: bacteriophage alone, vancomycin alone, bacteriophage and vancomycin, and sham. At day 28 post-surgery, animals were euthanised for microbiological and immunological assessment of implanted joints. Treatment with phage alone or vancomycin alone, led to 5-fold and 6.2-fold reductions, respectively in bacterial load within peri-implant tissue compared to shamtreated animals. Compared to sham-treated animals, a 22.5-fold reduction in S. aureus burden was observed within joint tissue of animals that were administered phage in combination with vancomycin, corresponding with decreased swelling in the implanted knee. Microbiological data were supported by evidence of decreased inflammation within the joints of animals administered phage in combination with vancomycin, compared to sham-treated animals. Our findings provide further support for phage therapy as a tolerable and effective adjunct treatment for PJI

Towards third generation matrix metalloproteinase inhibitors for cancer therapy

The failure of matrix metalloproteinase (MMP) inhibitor drug clinical trials in cancer was partly due to the inadvertent inhibition of MMP antitargets that counterbalanced the benefits of MMP target inhibition. We explore how MMP inhibitor drugs might be developed to achieve potent selectivity for validated MMP targets yet therapeutically spare MMP antitargets that are critical in host protection

The Corinth Rift Laboratory, Greece (CRL): A Multidisciplinary Near Fault Observatory (NFO) on a Fast Rifting System

The western rift of Corinth (Greece) is one of the most active tectonic structures of the euro-mediterranean area. Its NS opening rate is 1.5 cm/yr ( strain rate of 10-6/yr) results into a high microseismicity level and a few destructive, M>6 earthquakes per century, activating a system of mostly north dipping normal faults. Since 2001, monitoring arrays of the European Corinth Rift Laboratory (CRL, www.crlab.eu) allowed to better track the mechanical processes at work, with short period and broad band seismometers, cGPS, borehole strainmeters, EM stations, …). The recent (300 kyr) tectonic history has been revealed by onland (uplifted fan deltas and terraces) and offshore geological studies (mapping, shallow seismic, coring), showing a fast evolution of the normal fault system. The microseismicity, dominated by swarms lasting from days to months, mostly clusters in a layer 1 to 3 km thick, between 6 and 9 km in depth, dipping towards north, on which most faults are rooting. The diffusion of the microseismicity suggests its triggering by pore pressure transients, with no or barely detected strain. Despite a large proportion of multiplets, true repeaters seem seldom, suggesting a minor contribution of creep in their triggering, although transient or steady creep is clearly detected on the shallow part of some majors faults. The microseismic layer may thus be an immature, downward growing detachment, and the dominant rifting mechanism might be a mode I, anelastic strain beneath the rift axis , for which a mechanical model is under development. Paleoseismological (trenching, paleoshorelines, turbidites), archeological and historical studies completed the catalogues of instrumental seismicity, motivating attempts of time dependent hazard assessment. The Near Fault Observatory of CRL is thus a multidisciplinary research infrastructure aiming at a better understanding and modeling of multiscale, coupled seismic/aseismic processes on fault systems.Grant for Researchers (CC) ID 188753