Cathodic voltage-controlled electrical stimulation and betadine decontaminate nosocomial pathogens from implant surfaces.

Periprosthetic joint infection (PJI) after total joint arthroplasty is a major concern requiring multiple surgeries and antibiotic interventions. Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli are the predominant causes of these infections. Due to biofilm formation, antibiotic treatment for patients with PJI can prolong resistance, further complicating the use of current treatments. Previous research has shown that cathodic voltage-controlled electrical stimulation (CVCES) is an effective technique to prevent/treat implant-associated biofilm infections on titanium (Ti) surfaces. This study thus evaluated the efficacy of CVCES via the use of 10% betadine alone and in combination with CVCES to eradicate lab-grown biofilms on cemented and cementless cobalt-chromium (CoCr) and Ti surfaces. CVCES treatment alone for 24 hours demonstrated no detectable CFU for E. coli and P. aeruginosa biofilms on cementless CoCr implants. In the presence of cement, E. coli biofilms had 106 CFUs/implant remaining after CVCES treatment alone; however, P. aeruginosa biofilms on cemented implants were reduced to below detectable limits. The use of 10% betadine treatment for 3 minutes followed by 24-hour CVCES treatment brought CFU levels to below detectable limits in E. coli and P. aeruginosa. The same was true for S. aureus biofilms on cementless patellofemoral implants as well as femoral and tibial implants. These treatment methods were not sufficient for eradication of S. aureus biofilms on cemented implants. These results suggest that CVCES alone and CVCES with 10% betadine are effective approaches to treating biofilms formed by certain bacterial species potentially leading to the treatment of PJI.IMPORTANCEPeriprosthetic joint infections (PJIs) are problematic due to requiring multiple surgeries and antibiotic therapies that are responsible for increased patient morbidity and healthcare costs. These infections become resistant to antibiotic treatment due to the formation of biofilms on the orthopedic surfaces. Cathodic voltage-controlled electrical stimulation (CVCES) has previously been shown to be an effective technique to prevent and treat biofilm infections on different surfaces. This study shows that CVCES can increase the efficacy of 10% betadine irrigation used in debridement, antibiotics, and implant retention by 99.9% and clear infection to below detection limits. PJI treatments are at times limited, and CVCES could be a promising technology to improve patient outcomes.

UBL/UBA ubiquitin receptor proteins bind a common tetraubiquitin chain.

The ubiquitin-proteasome pathway is essential throughout the life cycle of a cell. This system employs an astounding number of proteins to ubiquitylate and to deliver protein substrates to the proteasome for their degradation. At the heart of this process is the large and growing family of ubiquitin receptor proteins. Within this family is an intensely studied group that contains both ubiquitin-like (UBL) and ubiquitin-associated (UBA) domains: Rad23, Ddi1 and Dsk2. Although UBL/UBA family members are reported to regulate the degradation of other proteins, their individual roles in ubiquitin-mediated protein degradation has proven difficult to resolve due to their overlapping functional roles and interaction with each other and other ubiquitin family members. Here, we use a combination of NMR spectroscopy and molecular biology to reveal that Rad23 and Ddi1 interact with each other by using UBL/UBA domain interactions in a manner that does not preclude their interaction with ubiquitin. We demonstrate that UBL/UBA proteins can bind a common tetraubiquitin molecule and thereby provide strong evidence for a model in which chains adopt an opened structure to bind multiple receptor proteins. Altogether our results suggest a mechanism through which UBL/UBA proteins could protect chains from premature de-ubiquitylation and unnecessary elongation during their transit to the proteasome.