ABSTRACT
A delicate balance between genome stability and instability ensures genome integrity while generating genetic diversity, a critical step for evolution. Indeed, while excessive genome instability is harmful, moderated genome instability can drive adaptation to novel environments by maximising genetic variation. Candida albicans, a human fungal pathogen that colonises different parts of the human body, adapts rapidly and frequently to different hostile host microenvironments. In this organism, the ability to generate large-scale genomic variation is a key adaptative mechanism triggering dangerous infections even in the presence of antifungal drugs. Understanding how fitter novel karyotypes are selected is key to determining how C. albicans and other microbial pathogens establish infections. Here, we identified the SUMO protease Ulp2 as a regulator of C. albicans genome integrity through genetic screening. Deletion of ULP2 leads to increased genome instability, enhanced genome variation and reduced fitness in the absence of additional stress. The combined stress caused by the lack of ULP2 and antifungal drug treatment leads to the selection of adaptive segmental aneuploidies that partially rescue the fitness defects of ulp2Δ/Δ cells. Short and long-read genomic sequencing demonstrates that these novel genotypes are selected via a two-step process leading to the formation of novel chromosomal fragments with breakpoints at microhomology regions and DNA repeats.
Subject(s)
Candida albicans , Peptide Hydrolases , Aneuploidy , Antifungal Agents , Candida albicans/genetics , Endopeptidases/genetics , Genomic Instability/genetics , Peptide Hydrolases/geneticsABSTRACT
We describe the case of a 26-year-old patient with a perivascular epithelioid cell tumour (PEComa) involving the 5th lumbar vertebra. Radiological findings, pathological features and treatment are presented. We conclude that PEComas should be considered in the differential diagnosis of vertebral lesions.
Subject(s)
Lumbar Vertebrae , Perivascular Epithelioid Cell Neoplasms/diagnosis , Spinal Neoplasms/diagnosis , Adult , Bone Cements , Decompression, Surgical , Diagnosis, Differential , Humans , Magnetic Resonance Imaging , Male , Perivascular Epithelioid Cell Neoplasms/pathology , Perivascular Epithelioid Cell Neoplasms/surgery , Spinal Neoplasms/pathology , Spinal Neoplasms/surgery , Tomography, X-Ray Computed , Vertebroplasty/methodsABSTRACT
Facet joint cysts are commonest at the L4-L5 level and are associated with facet joint degeneration and type III (degenerative) spondylolisthesis. It is extremely rare for facet joint cysts to cause symptomatic cauda equina compression. Three elderly patients presented to us with significant cauda equina compression caused by facet joint cysts. One presented with classic symptoms and signs of a cauda equina syndrome, a second with bilateral lower limb neurologic loss associated with uncontrolled epilepsy, and the third with bilateral leg symptoms as well as an upper limb tremor and fasciculation. The diagnosis was easily made after magnetic resonance scanning in two patients, although in one patient, it was significantly delayed because of his confounding neurologic picture. Lumbar spine surgery (decompression and cyst resection) was successful in resolving symptoms in all three, even though two patients had significant neurologic compromise before surgery. The occurrence of facet joint cysts in older patients can be associated with other degenerative neurologic conditions, and the diagnosis might not be apparent early. We suggest that in older patients who have a mixed picture of central and peripheral neurologic compromise, this diagnosis should be considered and investigation of the whole of the spine, not just the brain and spinal cord, should be undertaken.
