Hydroxamate production as a high affinity iron acquisition mechanism in Paracoccidioides Spp.

Iron is a micronutrient required by almost all living organisms, including fungi. Although this metal is abundant, its bioavailability is low either in aerobic environments or within mammalian hosts. As a consequence, pathogenic microorganisms evolved high affinity iron acquisition mechanisms which include the production and uptake of siderophores. Here we investigated the utilization of these molecules by species of the Paracoccidioides genus, the causative agents of a systemic mycosis. It was demonstrated that iron starvation induces the expression of Paracoccidioides ortholog genes for siderophore biosynthesis and transport. Reversed-phase HPLC analysis revealed that the fungus produces and secretes coprogen B, which generates dimerumic acid as a breakdown product. Ferricrocin and ferrichrome C were detected in Paracoccidioides as the intracellular produced siderophores. Moreover, the fungus is also able to grow in presence of siderophores as the only iron sources, demonstrating that beyond producing, Paracoccidioides is also able to utilize siderophores for growth, including the xenosiderophore ferrioxamine. Exposure to exogenous ferrioxamine and dimerumic acid increased fungus survival during co-cultivation with macrophages indicating that these molecules play a role during host-pathogen interaction. Furthermore, cross-feeding experiments revealed that Paracoccidioides siderophores promotes growth of Aspergillus nidulans strain unable to produce these iron chelators. Together, these data denote that synthesis and utilization of siderophores is a mechanism used by Paracoccidioides to surpass iron limitation. As iron paucity is found within the host, siderophore production may be related to fungus pathogenicity

The small noncoding RNAs (sncRNAs) of murine gammaherpesvirus 68 (MHV-68) are involved in regulating the latent-to-lytic switch in vivo

The human gammaherpesviruses Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), which are associated with a variety of diseases including tumors, produce various small noncoding RNAs (sncRNAs) such as microRNAs (miRNAs). Like all herpesviruses, they show two stages in their life cycle: lytic replication and latency. During latency, hardly any viral proteins are expressed to avoid recognition by the immune system. Thus, sncRNAs might be exploited since they are less likely to be recognized. Specifically, it has been proposed that sncRNAs might contribute to the maintenance of latency. This has already been shown in vitro, but the respective evidence in vivo is very limited. A natural model system to explore this question in vivo is infection of mice with murine gammaherpesvirus 68 (MHV-68). We used this model to analyze a MHV-68 mutant lacking the expression of all miRNAs. In the absence of the miRNAs, we observed a higher viral genomic load during late latency in the spleens of mice. We propose that this is due to a disturbed regulation of the latent-to-lytic switch, altering the balance between latent and lytic infection. Hence, we provide for the first time evidence that gammaherpesvirus sncRNAs contribute to the maintenance of latency in vivo

Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine

Serous detection of the neuroretina in Waldenström disease. A case report [in German]

BACKGROUND: Waldenstrom's Macroglobulinemia is a monoclonal gammopathy producing pathologic IgM antibodies with increased blood viscosity, platelet dysfunction and retinal hemorrhages. As a complication a serous detachment of the macula is described. The pathogenesis of the serous detachment is still not fully understood. CASE REPORT: A 73-year-old male patient was presented with Waldenstrom's Macroglobulinemia, a typical hyperviscosity retinopathy and serous detachment of the macula. We performed fluorescein (FA)- and indocyaningreenangiography (ICG) before and three months after chemotherapy. Especially ICG-angiographic findings revealed a serous detachment that was restricted to the posterior pole but showed a fingershaped enlargement to the optic disc. CONCLUSION: FA- and especially ICG-angiographic findings can help to get more information about the pathogenetic mechanism of serous detachment in Waldenstrom's Macroglobulinemia. Besides toxic alteration of the retinal pigmentepithelium, oncotic and hydrostatic pressure, a pathologic communication between the optic disc, the subarachnoid space and the subretinal space is discussed

Multifocal ERG in central areolar choroidal dystrophy [in German]

BACKGROUND: In comparison to full-field ERG a multifocal ERG (mf-ERG) provides functional mapping of the central retina and detection of more localised defects. Central areolar choroidal dystrophy is an autosomal dominant inherited disorder with central atrophy of the choriocapillaries, the retinal pigment epithelium (RPE) and the photoreceptors. Full-field ERG often shows only slight to moderate reductions. The purpose of our study was to investigate the electroretinographic activity of the posterior pole with the mf-ERG in comparison to the photopic full-field ERG in these patients. PATIENTS AND METHODS: We performed a mf-ERG and a photopic full-field ERG in 4 patients with central areolar choroidal dystrophy and in 20 age-matched volunteers who constituted the normal control group. RESULTS: In all patients reductions in b-wave amplitudes of the first order kernel of the mf-ERG in both eyes were evident. Full-field ERG showed decreased b-wave amplitudes in only three eyes. Subnormal amplitudes were found in two eyes and normal amplitudes in three eyes. Additionally ophthalmoscopic lesions were found to a lesser extent than by the mf-ERG. DISCUSSION: The mf-ERG is a valuable tool in detecting central areolar choroidal dystrophy and might be useful in early detection and follow-up, when ophthalmoscopy and full-field ERG are still normal. Moreover it could contribute to differential diagnosis of other retinal diseases of the posterior pole

Optical coherence tomography (OCT) in acute macular neuroretinopathy

PURPOSE: To evaluate the value of ocular coherence tomography (OCT) concerning diagnosis and pathogenesis of acute macular neuroretinopathy. METHODS: A 33-year old woman complained of sudden onset of central scotomas in her right eye because of acute macular neuroretinopathy. We performed a direct ophthalmoscopy, a visual field testing, a fluorescein angiography (FA) a multifocal ERG (mf-ERG) and an OCT. RESULTS: We found typical paracentral scotoma in visual field testing, a normal FA and mf-ERG in her right eye. In OCT there was a band of higher reflectivity (115 microm) overlying an intact band corresponding to the retinal pigment epithelium (RPE)/ choriocapillaris complex. Retinal thickness was within the normal range. CONCLUSION: OCT can be an additional valuable tool in acute macular neuroretinopathy as it is a disease with discrete pathology and often normal results in other diagnostic tests