65 research outputs found

    The cytochrome bd-I respiratory oxidase augments survival of multidrug-resistant Escherichia coli during infection

    Get PDF
    Nitric oxide (NO) is a toxic free radical produced by neutrophils and macrophages in response to infection. Uropathogenic Escherichia coli (UPEC) induces a variety of defence mechanisms in response to NO, including direct NO detoxification (Hmp, NorVW, NrfA), iron-sulphur cluster repair (YtfE), and the expression of the NO-tolerant cytochrome bd-I respiratory oxidase (CydAB). The current study quantifies the relative contribution of these systems to UPEC growth and survival during infection. Loss of the flavohemoglobin Hmp and cytochrome bd-I elicit the greatest sensitivity to NO-mediated growth inhibition, whereas all but the periplasmic nitrite reductase NrfA provide protection against neutrophil killing and promote survival within activated macrophages. Intriguingly, the cytochrome bd-I respiratory oxidase was the only system that augmented UPEC survival in a mouse model after 2 days, suggesting that maintaining aerobic respiration under conditions of nitrosative stress is a key factor for host colonisation. These findings suggest that while UPEC have acquired a host of specialized mechanisms to evade nitrosative stresses, the cytochrome bd-I respiratory oxidase is the main contributor to NO tolerance and host colonisation under microaerobic conditions. This respiratory complex is therefore of major importance for the accumulation of high bacterial loads during infection of the urinary tract

    Asymptomatic presentation of mesalamine-induced lung injury in an adolescent with Crohn disease

    No full text
    The present report describes the case of a 14-year-old boy receiving mesalamine for Crohn disease who was discovered to have incidental pulmonary infiltrates on chest radiograph and CT scan shortly after increasing the dose of this medication. Despite the significant radiographic abnormalities, he had no respiratory symptoms. He had normal oxygenation and normal pulmonary function tests including spirometry, lung volumes and diffusion capacity. Transbronchial biopsies showed patchy interstitial fibrosis with ill-defined non-necrotising granulomas and lymphoid aggregates. Pulmonary infiltrates resolved within 6 weeks of discontinuation of mesalamine and the addition of low-dose daily corticosteroids. This case likely represents an asymptomatic “early stage” of mesalamine-induced lung injury preceding the onset of symptoms. Alternatively, mesalamine may induce asymptomatic lung injury more commonly than is presently suspected. To the best of our knowledge this is the first time this complication has been reported without respiratory symptoms
    • …
    corecore