A spinal epidural abscess due to Streptobacillus moniliformis infection following a rat bite: case report.

The authors describe the case of a 40-year-old man suffering from an epidural abscess in the thoracic spine due to a rarely isolated pathogen, Streptobacillus moniliformis, the causative agent of rat bite fever. Besides diffuse abdominal pain, ataxia, paresthesia, hypesthesia, and enhanced reflexes of the lower extremities, the patient suffered from a decreased sensation of bladder filling. His history was also positive for a rat bite 6 weeks earlier. Magnetic resonance imaging showed an epidural, space-occupying lesion compressing the spinal cord at the vertebral levels of T6-8. Neurosurgery revealed an epidural abscess, which was drained via laminectomy (T-7) and excision of the ligamentum flavum (T6-8). The etiological agent S. moniliformis was identified by 16S rRNA-based polymerase chain reaction and sequencing as well as by culture and mass spectrometry. Treatment with penicillin G led to complete resolution of the abscess and clinical recovery of the patient, who regained his bladder-filling sensation and free walking ability. This case demonstrates that careful attention to the patient's history is essential in suspecting unusual bacterial pathogens as the cause of an epidural abscess and initiating the optimal diagnostic procedure and antimicrobial therapy.

Deletions in the cytoplasmic domain of iRhom1 and iRhom2 promote shedding of the TNF receptor by the protease ADAM17.

The protease ADAM17 (a disintegrin and metalloproteinase 17) catalyzes the shedding of various transmembrane proteins from the surface of cells, including tumor necrosis factor (TNF) and its receptors. Liberation of TNF receptors (TNFRs) from cell surfaces can dampen the cellular response to TNF, a cytokine that is critical in the innate immune response and promotes programmed cell death but can also promote sepsis. Catalytically inactive members of the rhomboid family of proteases, iRhom1 and iRhom2, mediate the intracellular transport and maturation of ADAM17. Using a genetic screen, we found that the presence of either iRhom1 or iRhom2 lacking part of their extended amino-terminal cytoplasmic domain (herein referred to as ΔN) increases ADAM17 activity, TNFR shedding, and resistance to TNF-induced cell death in fibrosarcoma cells. Inhibitors of ADAM17, but not of other ADAM family members, prevented the effects of iRhom-ΔN expression. iRhom1 and iRhom2 were functionally redundant, suggesting a conserved role for the iRhom amino termini. Cells from patients with a dominantly inherited cancer susceptibility syndrome called tylosis with esophageal cancer (TOC) have amino-terminal mutations in iRhom2. Keratinocytes from TOC patients exhibited increased TNFR1 shedding compared with cells from healthy donors. Our results explain how loss of the amino terminus in iRhom1 and iRhom2 impairs TNF signaling, despite enhancing ADAM17 activity, and may explain how mutations in the amino-terminal region contribute to the cancer predisposition syndrome TOC.