Browsing by Author "Schell, Wiley A"
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Item Open Access Diagnostic difficulty identifying Apophysomyces trapeziformis septic arthritis in a patient with multiple myeloma.(JMM case reports, 2016-12-19) Bertumen, J Bradford; Schell, Wiley A; Joyce, Maria; Alley, Christopher; Woods, Christopher WINTRODUCTION:Mucormycosis is a rare fungal infection, but can cause substantial morbidity and mortality in both immunocompromised and immunocompetent patients. Apophysomyces is a mucormycetes species ubiquitous in nature, particularly in soil, decaying wood and other organic matter. Apophysomyces is known to cause cutaneous fungal infections, particularly after penetrating trauma. Septic arthritis is a rare clinical manifestation. CASE PRESENTATION:We describe a case of Apophysomyces trapeziformis causing septic arthritis of the knee of a patient with multiple myeloma. He was treated multiple times for bacterial septic arthritis with minimal improvement. Surgical tissue specimens finally grew mucoraceous mould, and DNA sequencing and morphological assessment of spores identified the mould as A. trapeziformis. The patient was treated with amphotericin B and posaconazole, but ultimately required an above-the-knee amputation for definitive treatment. CONCLUSION:This case illustrates the need to evaluate for fungal infection in a persistent septic arthritis that is culture negative and refractory to empiric antibiotics, particularly in an immunocompromised individual. It also shows the importance of a thorough social history and adequate tissue specimens for culture.Item Open Access Curvularia alcornii Aortic Pseudoaneurysm Following Aortic Valve Replacement: Case Report and Review of the Literature.(Open forum infectious diseases, 2021-11) Narayanasamy, Shanti; Williams, Adam R; Schell, Wiley A; Moehring, Rebekah W; Alexander, Barbara D; Le, Thuy; Bharadwaj, Ramesh A; McGauvran, Michelle; Schroder, Jacob N; Perfect, John RWe report the first case of Curvularia alcornii aortic pseudoaneurysm following bioprosthetic aortic valve replacement in an immunocompetent host. Infection was complicated by septic emboli to multiple organs. Despite aggressive surgical intervention and antifungal therapy, infection progressed. We review the literature on invasive Curvularia infection to inform diagnosis and management.Item Open Access Microfluidic platform versus conventional real-time polymerase chain reaction for the detection of Mycoplasma pneumoniae in respiratory specimens.(Diagn Microbiol Infect Dis, 2010-05) Wulff-Burchfield, Elizabeth; Schell, Wiley A; Eckhardt, Allen E; Pollack, Michael G; Hua, Zhishan; Rouse, Jeremy L; Pamula, Vamsee K; Srinivasan, Vijay; Benton, Jonathan L; Alexander, Barbara D; Wilfret, David A; Kraft, Monica; Cairns, Charles B; Perfect, John R; Mitchell, Thomas GRapid, accurate diagnosis of community-acquired pneumonia (CAP) due to Mycoplasma pneumoniae is compromised by low sensitivity of culture and serology. Polymerase chain reaction (PCR) has emerged as a sensitive method to detect M. pneumoniae DNA in clinical specimens. However, conventional real-time PCR is not cost-effective for routine or outpatient implementation. Here, we evaluate a novel microfluidic real-time PCR platform (Advanced Liquid Logic, Research Triangle Park, NC) that is rapid, portable, and fully automated. We enrolled patients with CAP and extracted DNA from nasopharyngeal wash (NPW) specimens using a biotinylated capture probe and streptavidin-coupled magnetic beads. Each extract was tested for M. pneumoniae-specific DNA by real-time PCR on both conventional and microfluidic platforms using Taqman probe and primers. Three of 59 (5.0%) NPWs were positive, and agreement between the methods was 98%. The microfluidic platform was equally sensitive but 3 times faster and offers an inexpensive and convenient diagnostic test for microbial DNA.Item Open Access PKC signaling regulates drug resistance of the fungal pathogen Candida albicans via circuitry comprised of Mkc1, calcineurin, and Hsp90.(PLoS Pathog, 2010-08-26) LaFayette, Shantelle L; Collins, Cathy; Zaas, Aimee K; Schell, Wiley A; Betancourt-Quiroz, Marisol; Gunatilaka, AA Leslie; Perfect, John R; Cowen, Leah EFungal pathogens exploit diverse mechanisms to survive exposure to antifungal drugs. This poses concern given the limited number of clinically useful antifungals and the growing population of immunocompromised individuals vulnerable to life-threatening fungal infection. To identify molecules that abrogate resistance to the most widely deployed class of antifungals, the azoles, we conducted a screen of 1,280 pharmacologically active compounds. Three out of seven hits that abolished azole resistance of a resistant mutant of the model yeast Saccharomyces cerevisiae and a clinical isolate of the leading human fungal pathogen Candida albicans were inhibitors of protein kinase C (PKC), which regulates cell wall integrity during growth, morphogenesis, and response to cell wall stress. Pharmacological or genetic impairment of Pkc1 conferred hypersensitivity to multiple drugs that target synthesis of the key cell membrane sterol ergosterol, including azoles, allylamines, and morpholines. Pkc1 enabled survival of cell membrane stress at least in part via the mitogen activated protein kinase (MAPK) cascade in both species, though through distinct downstream effectors. Strikingly, inhibition of Pkc1 phenocopied inhibition of the molecular chaperone Hsp90 or its client protein calcineurin. PKC signaling was required for calcineurin activation in response to drug exposure in S. cerevisiae. In contrast, Pkc1 and calcineurin independently regulate drug resistance via a common target in C. albicans. We identified an additional level of regulatory control in the C. albicans circuitry linking PKC signaling, Hsp90, and calcineurin as genetic reduction of Hsp90 led to depletion of the terminal MAPK, Mkc1. Deletion of C. albicans PKC1 rendered fungistatic ergosterol biosynthesis inhibitors fungicidal and attenuated virulence in a murine model of systemic candidiasis. This work establishes a new role for PKC signaling in drug resistance, novel circuitry through which Hsp90 regulates drug resistance, and that targeting stress response signaling provides a promising strategy for treating life-threatening fungal infections.Item Open Access Pulmonary blastomycosis presenting as primary lung cancer.(BMC infectious diseases, 2018-07-18) Hussaini, Syed Mohammed Qasim; Madut, Deng; Tong, Betty C; Pavlisko, Elizabeth N; Schell, Wiley A; Perfect, John R; Thielman, Nathan MBACKGROUND:Blastomycosis is an endemic mycosis in North America that is caused by the dimorphic fungus Blastomyces dermatitidis. The illness is a systemic disease with a wide variety of pulmonary and extra-pulmonary manifestations. The initial presentation of blastomycosis may easily be mistaken for other infectious or non-infectious etiologies. CASE PRESENTATION:We present the case of a 52-year-old African-American male and former smoker that presented to his primary care provider with a 2-week history of non-productive cough, night sweats and weight loss. Initially diagnosed with primary lung malignancy, the patient was subsequently found to have pulmonary blastomycosis mimicking lung cancer. The patient underwent a successful course of treatment with posaconazole. CONCLUSIONS:Chronic blastomycosis can present with clinical and radiographic features indistinguishable from thoracic malignancies. There is no clinical syndrome specific for blastomycosis, thus a high degree of suspicion is required for early diagnosis. In this case report, we review recent evidence in radiographic features, diagnostic considerations and treatment of the disease.