Interaction between pairs of Staphylococcus aureus replication proteins was detected in an Escherichia coli based two-hybrid analysis. A reverse two-hybrid system was constructed for selection of compounds that hindered interaction between interacting protein pairs. A number of cyclic peptides, from a library generated by the split intein-mediated circular ligation of peptides and proteins technology, were found to interfere with dimerization of the β-sliding clamp of the replisome. Two 8-mer peptides were analyzed in more detail. Both inhibited DNA replication, led to SOS induction, altered cell morphology and cell death. The peptides were active when added to bacterial cultures indicating that they could traverse the bacterial membrane to find their intracellular target. Peptide specificity was confirmed by overproduction of the putative target (DnaN) which resulted in resistance. The minimum inhibitory concentration was ∼50 μg/ml for S. aureus cells. These compounds may serve as lead candidates for future development into novel classes of antibiotics as well as provide information on the function of the S. aureus replication process.
Background
Major incidents (MI) are rare occurrences in Scandinavia. Literature depicting Scandinavian MI management is scarce and case reports and research is called for. In 2019, a trailer falling off a freight train struck a passing high-speed train on the Great Belt Bridge in Denmark, killing eight people instantly and injuring fifteen people. We aim to describe the emergency medical services (EMS) response to this MI and evaluate adherence to guidelines to identify areas of improvement for future MI management.
Case presentation
Nineteen EMS units were dispatched to the incident site. Ambulances transported fifteen patients to a trauma centre after evacuation. Deceased patients were pronounced life-extinct on-scene. Radio communication was partly compromised, since 38.9% of the radio shifts were not according to the planned radio grid and presented a potential threat to patient outcome and personnel safety. Access to the incident site was challenging and delayed due to traffic congestion and safety issues.
Conclusion
Despite harsh weather conditions and complex logistics, the availability of EMS units was sufficient and patient treatment and evacuation was uncomplicated. Triage was relevant, but at the physicians’ discretion. Important findings were communication challenges and the consequences of difficult access to the incident site. There is a need for an expansion of capacity in formal education in MI management in Denmark.
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