28 research outputs found

    Recurrent N209* ABHD5 mutation in two unreported families with Chanarin Dorfman Syndrome

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    ABHD5 protein is widely involved in lipid and energy homeostasis. Mutations in the ABHD5 gene are associated with the onset of Neutral Lipid Storage Disease with Ichthyosis (NLSDI), historically known as Chanarin Dorfman Syndrome (CDS). CDS is a rare autosomal recessive lipid storage disease, characterized by non-bullous congenital ichthyosiform eritrhoderma (NCIE), hepatomegaly and liver steatosis. Myopathy, neurosensory hearing loss, cataracts, nystagmus, strabismus, and mental impairment are considered additional findings. To date, 151 CDS patients have been reported all over the world. Here we described two additional families with patients affected by CDS from Turkey. Our patients were a 42 and 22-years old men, admitted to the Hospital for congenital ichthyosis. Hepatic steatosis and myopathy were also detected in both patients. ABHD5 molecular analysis revealed the presence of N209* mutation. Our data enlarge the cohort of CDS patients and provide a revision of muscle clinical findings for this rare inborn error of neutral lipid metabolism

    Brouwer’s satellite solution redux

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    Genomic island discovery in Shigella by tRNA site interrogation

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    Introduction: Shigella spp. are pathogenic variants of Escherichia coli that cause bacillary dysentery, resulting in more than 1 million deaths per year. E. coli bacteria demonstrate extensive intra-species genodiversity. The dynamic process of acquisition and loss of genomic islands (GIs), especially those associated with virulence (pathogenicity islands [PAIs]) is a driving force behind the emergence of new pathotypes. In Shigella only 4 GIs have been well characterised and there is currently no effective vaccine against the many serotypes of this pathogen. Therefore the development of an effective screen to detect GIs in unsequenced Shigella strains could be highly informative. In this study, 16 known E. coli tRNA gene integration hotspots in 10 strains representative of the 4 ‘species’ of Shigella were probed for the presence of island DNA using a high throughput PCR screen known as tRNA site Interrogation for PAIs, prophages and other GIs (tRIP). Putative GIs were then investigated using a chromosome walking technique known as single genome-specific primer-PCR (SGSP-PCR)

    CpxR promotes the carbapenem antibiotic resistance of <i>Klebsiella pneumoniae</i> by directly regulating the expression and the dissemination of <i>bla</i><sub>KPC</sub> on the IncFII conjugative plasmid

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    Klebsiella pneumoniae is an important human pathogen known for its resistance to carbapenem antibiotics, especially the increasing carbapenem-resistant hypervirulent variants. The carbapenem resistance is mainly caused by the carbapenemase gene blaKPC which was commonly found on the IncFII transferable plasmids in K. pneumoniae ST11 isolates in regions of China. However, the mechanisms of the plasmid-carrying blaKPC regulation by the host strain are not clear. To investigate the chromosome-encoded two-component system (TCS) that regulates the carbapenem resistance of K. pneumoniae caused by blaKPC, twenty-four TCSs of a carbapenem-resistant classical K. pneumoniae ST11 clinical isolate were knocked out. The deletion mutation of the TCS regulator cpxR exhibited increased sensitivity to carbapenem, which could be restored by complementation with cpxR in trans. Electrophoretic mobility shift, isothermal titration calorimetry and DNase I footprinting results revealed that CpxR directly bound to the promoter DNA of blaKPC and the binding was abolished by disrupting the DNA-binding domain in CpxR. The subsequent in vivo assays using the lacZ reporter system and qPCR showed that CpxR upregulates the transcription of blaKPC. Notably, CpxR was also found to activate the transfer of the blaKPC-carrying IncFII plasmid between the hypervirulent K. pneumoniae and E. coli isolates, in which CpxR promoted the transcription of the tra operon via binding to its promoter region. These results provide an important insight into the regulation of the host factor CpxR in the plasmid-carrying carbapenemase gene in the classical and hypervirulent K. pneumoniae.</p