Krause, F. F. | bioRxiv Science

bioRxiv2025

OXA-1207, a new OXA-48-type carbapenem-hydrolysing class D beta lactamase from Escherichia coli

1.We present the characterisation of OXA-1207, a novel, plasmid-encoded OXA-48-like carbapenemase identified in two unrelated Escherichia coli (sequence type (ST) ST405 and ST4405) isolates from hospital patients in Germany. OXA-1207 is closely related to OXA-181, differing by two amino acid substitutions (214G and 244W). The blaOXA-1207 gene was located on a self-transmissible IncFIC plasmids (pOXA-1207) featuring a conserved backbone and the novel {Delta}Tn6361 transposon structure, which derived from IncX3 plasmids carrying blaOXA-181. Notably, pOXA-1207 exhibited an exceptionally high conjugation frequency (mean 1.2 x 10-1) to E. coli, surpassing the typical rates reported for widely distributed OXA-48 plasmids. Analysis of public genomic datasets identified 40 E. coli isolates carrying blaOXA-1207, belonging to diverse high-risk clonal lineages (ST167, ST405 and ST410). The isolates originated from multiple continents, indicating global dissemination. These findings highlight OXA-1207 as an emerging and concerning resistance determinant with enhanced transmissibility and emphasise the need for continued molecular surveillance of OXA-48-like carbapenemases.

microbiology↗

bioRxiv2023

Immunoproteasome deficiency results in accelerated brain aging and epilepsy

The immunoproteasome is a central protease complex required for optimal antigen presentation. Immunoproteasome activity is also associated with facilitating degradation of misfolded and oxidized proteins, which prevents cellular stress. While extensively studied during diseases with increasing evidence suggesting a role for the immunoproteasome during pathological conditions including neurodegenerative diseases, this enzyme complex is believed to be mainly inactive in the healthy brain. Here, we show an age-dependent increase in polyubiquitination in the brain of wild-type mice, accompanied with induction of immunoproteasomes, which was most prominent in neurons and microglia. In contrast, mice completely lacking immunoproteasomes (triple-knockout (TKO) mice deficient for LMP2, LMP7 and MECL-1), displayed a strong increase in polyubiquitinated proteins already in the young brain and developed spontaneous epileptic seizures, beginning at the age of 6 months. Injections of kainic acid led to high epilepsy-related mortality of aged TKO mice, confirming increased pathological hyperexcitability states. Notably, the expression of the immunoproteasome was reduced in the brains of patients suffering from epilepsy. In addition, aged TKO mice showed increased anxiety, tau hyperphosphorylation and degeneration of Purkinje cell population with the resulting ataxic symptoms and locomotion alterations. Collectively, our study suggests a critical role for the immunoproteasome in the maintenance of a healthy brain during aging.

neuroscience↗