Bacterial c-di-GMP has a key role in establishing host-microbe symbiosis.

Most microbes evolve faster than their hosts and should therefore drive evolution of host-microbe interactions. However, relatively little is known about the characteristics that define the adaptive path of microbes to host association. Here we identified microbial traits that mediate adaptation to hosts by experimentally evolving the free-living bacterium Pseudomonas lurida with the nematode Caenorhabditis elegans as its host. After ten passages, we repeatedly observed the evolution of beneficial host-specialist bacteria, with improved persistence in the nematode being associated with increased biofilm formation. Whole-genome sequencing revealed mutations that uniformly upregulate the bacterial second messenger, cyclic diguanylate (c-di-GMP). We subsequently generated mutants with upregulated c-di-GMP in different Pseudomonas strains and species, which consistently increased host association. Comparison of pseudomonad genomes from various environments revealed that c-di-GMP underlies adaptation to a variety of hosts, from plants to humans. This study indicates that c-di-GMP is fundamental for establishing host association.

Novel Bone-Anchored Vascular Access on the Mastoid for Hemodialysis: Concept and Preclinical Trials.

GOAL: We present the development of a bone-anchored port for the painless long-term hemodialytic treatment of patients with renal failure. This port is implanted behind the ear. METHODS: The port was developed based on knowledge obtained from long-term experience with implantable hearing devices, which are firmly anchored to the bone behind the ear. This concept of bone anchoring was adapted to the requirements for a vascular access during hemodialysis. The investigational device is comprised of a base plate that is firmly fixed with bone screws to the bone behind the ear (temporal bone). A catheter leads from the base plate valve block through the internal jugular vein and into the right atrium. The valves are opened using a special disposable adapter, without any need to puncture the blood vessels. Between hemodialysis sessions, the port is protected with a disposable cover. RESULTS: Flow rate, leak tightness, and purification were tested on mockups. Preoperative planning and the surgical procedure were verified in 15 anatomical human whole head specimens. CONCLUSION: Preclinical evaluations demonstrated the technical feasibility and safety of the investigational device. SIGNIFICANCE: Approximately 1.5 million people are treated with hemodialysis worldwide, and 25% of the overall cost of dialysis therapy results from vascular access problems. New approaches toward enhancing vascular access could potentially reduce the costs and complications of hemodialytic therapy.

[A new bone anchored hemodialysis access]. / Neuartiger knochenverankerter Hämodialysezugang.

When classic arteriovenous fistulas or grafts fail, dialysis patients have a vital requirement for a catheter to ensure vascular access. Permanent central venous catheters penetrate the cervical and thoracic soft tissues and the skin without rigid fixation. The infection rate for such devices is high, often requiring explantation. Bone anchored hearing aids are an established treatment in patients with conductive hearing loss. The implant is firmly fixed on the temporal bone and the abutment permanently penetrates the skin. Severe infections requiring explantation are very rare. We suppose that one of the main reasons for the low complication rate is the firm fixation of the implant to the temporal bone, which minimizes the movement of the skin relative to the underlying bone. Based on the experience with implantable hearing devices we developed a percutaneous bone anchored port fixed to the skull in the region of the temporal bone. Such a bone anchored port could be a beneficial alternative to conventional central venous catheters for patients undergoing hemodialysis. In the course of the development process we investigated the individual anatomy to locate the correct implantation site with sufficient bone thickness; we studied screw stability in bone; we developed the titanium implant that houses the port system as well as the surgical tools and procedure for save implantation; we tested flow rate, leak tightness and purification on mockups; we defined the Seldinger-insertion of the catheter into the internal jugular vein via a small neck incision. Our results show the technical feasibility of a temporal bone anchored port and form the basis of a now-approved clinical pilot study.