Certain mutant strains of herpes simplex virus type 1 (HSV-1) are unable to infect cells in which entry is dependent on HVEM, the previously described herpesvirus entry mediator designated here as herpesvirus entry protein A (HveA). These mutant viruses can infect other cells where entry is apparently dependent on other co-receptors. The mutant virus HSV-1(KOS)Rid1 was used to screen a human cDNA expression library for ability of transfected plasmids to convert resistant Chinese hamster ovary cells to susceptibility to virus entry. A plasmid expressing the previously described poliovirus receptor-related protein 2 (Prr2) was isolated on the basis of this activity. This protein, designated here as HveB, was shown to mediate the entry of three mutant HSV-1 strains that cannot use HVEM as co-receptor, but not wild-type HSV-1 strains. HveB also mediated the entry of HSV-2 and pseudorabies virus but not bovine herpesvirus type 1. HveB was expressed in some human neuronal cell lines, fibroblastic cells, keratinocytes, and primary activated T lymphocytes. Antibodies specific for HveB blocked infection of HveB-expressing CHO cells and a human fibroblastic cell strain HEL299. Differences in ability of HSV-1 and HSV-2 strains to use HveB for entry should influence the types of cells that can be infected and thereby account in part for serotype and strain differences in tissue tropism and pathogenicity.

Background: Diabetic foot ulcer (DFU) is a serious complication of diabetes mellitus. Antibiotic-resistantStaphylococcus aureusis frequently isolated from DFU infections. Bacteriophages (phages) represent an alternative or adjunct treatment to antibiotic therapy. Here we describe the efficacy of AB-SA01, a cocktail of threeS. aureus Myoviridaephages, made to current good manufacturing practice (cGMP) standards, and which has undergone two phase I clinical trials, in treatment of multidrug-resistant (MDR)S. aureusinfections.Results: Wounds of saline-treated mice showed no healing, but expanded and became inflamed, ulcerated, and suppurating. In contrast, AB-SA01 treatment decreased the bacterial load with efficacy similar or superior to vancomycin treatment. At the end of the treatment period, there was a significant decrease (p < 0.001) in bacterial load and wound size in infected phage- and vancomycin-treated groups compared with infected saline-treated mice. In phage-treated mice, wound healing was seen similar to vancomycin treatment. No mortality was recorded associated with infections, and post-mortem examinations did not show any evident pathological lesions other than the skin wounds. No adverse effects related to the application of phages were observed.Conclusion: Topical application of phage cocktail AB-SA01 is effective, as shown by bacterial load reduction and wound closure, in the treatment of diabetic wound infections caused by MDRS. aureus. Our results suggest that topical phage cocktail treatment may be effective in treating antibiotic-resistantS. aureusDFU infections.

The efficacy of phages in multispecies infections has been poorly examined. The in vitro lytic efficacies of phage cocktails AB-SA01, AB-PA01, which target Staphylococcus aureus and Pseudomonas aeruginosa, respectively, and their combination against their hosts were evaluated in S. aureus and P. aeruginosa mixed-species planktonic and biofilm cultures. Green fluorescent protein (GFP)-labelled P. aeruginosa PAO1 and mCherry-labelled S. aureus KUB7 laboratory strains and clinical isolates were used as target bacteria. During real-time monitoring using fluorescence spectrophotometry, the density of mCherry S. aureus KUB7 and GFP P. aeruginosa PAO1 significantly decreased when treated by their respective phage cocktail, a mixture of phage cocktails, and gentamicin. The decrease in bacterial density measured by relative fluorescence strongly associated with the decline in bacterial cell counts. This microplate-based mixed-species culture treatment monitoring through spectrophotometry combine reproducibility, rapidity, and ease of management. It is amenable to high-throughput screening for phage cocktail efficacy evaluation. Each phage cocktail, the combination of the two phage cocktails, and tetracycline produced significant biofilm biomass reduction in mixed-species biofilms. This study result shows that these phage cocktails lyse their hosts in the presence of non-susceptible bacteria. These data support the use of phage cocktails therapy in infections with multiple bacterial species.

Sudden and unexpected nontraumatic death in individuals with asplenia or hyposplenia is usually due to fulminant bacterial sepsis, most often involving Streptococcus pneumoniae, Neisseria meningitidis, and Hemophilus influenzae. We report a case of a previously well 40-year-old man who died 5 hours after hospital admission. At autopsy Waterhouse-Friderichsen syndrome was identified and Capnocytophaga canimorsus was subsequently isolated on antemortem blood cultures. Infection of humans with this organism is most often due to dog bite or contact. Upon specific inquiry it was ascertained that 2 days before admission the deceased had suffered a superficial bite to his hand by his pet Staffordshire Bullterrier dog. His relevant history included a previous splenectomy following blunt abdominal trauma. Asplenia and hyposplenia at autopsy should prompt microbiological testing with consideration of unusual organisms such as C. canimorsus. Although histories of animal contact or injury are often not available at the time of autopsy, this should also be considered in cases of apparent fulminant sepsis. In individuals with asplenia or hyposplenia, dog bites do not have to involve excessive tissue trauma, vascular compromise, or blood loss to be lethal.