DOCSLIB.ORG

Case Report. Atypical Cutaneous Pseudallescheriosis Refractory to Antifungal Agents

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Case Report. Atypical Cutaneous Pseudallescheriosis Refractory to Antifungal Agents mycoses 42, 507–511 (1999) Accepted: September 20, 1998 LETTER TO THE EDITOR Case Report. Atypical cutaneous pseudallescheriosis refractory to antifungal agents Fallbericht: Atypische therapierefrakta¨re kutane Pseudallescheriose Gabriele Ginter1, B. Petutschnig2, G. Pierer2, H. P. Soyer1, S. Reischle1, T. Kern1 and S. de Hoog3 Key words. Pseudallescheria boydii, cutaneous infection, heart transplant, antimycotic chemotherapy, itraconazole, miconazole, surgical debridement. Schlu¨ sselwo¨rter. Pseudallescheria boydii, Hautinfektion, Herztransplantation, antimykotische Chemotherapie, Itraconazol, Miconazol, chirurgisches Debridement. Summary. We report on a 65-year-old male Zusammenfassung. Bei einem 65-ja¨hrigen heart transplant recipient who was otherwise in herztransplantierten Patienten kam es unter good condition. The patient was immunocom- Immunsuppression mit Cyclosporin, Kortikoste- promised secondarily due to cyclosporin, predniso- roiden und Azathioprin 3 Monate nach Herztrans- lone and azathioprine when widespread pustular plantation bei gutem Allgemeinzustand zur skin lesions with erythematous margins sub- Entwicklung von Pusteln auf erythemato¨sem sequently developed on his left forearm. There Grund am linken Unterarm. Anamnestisch ergab was no history of trauma or septic temperature. sich kein Anhalt fu¨r ein zuvor erfolgtes Trauma Bacterial cultures were sterile and the results of oder febrile Temperaturen. Die mikrobiologische native and cultural investigation studies were nega- Exploration erbrachte weder nativ noch kulturell tive. A biopsy specimen of the lesion demonstrated einen Erregernachweis. In der feingeweblichen hyalohyphomycosis with numerous septate hyphae Untersuchung einer Hautbiopsie fanden sich im within granulomas throughout the dermis. Bereich der Dermis innerhalb von Granulomen Subcutaneous tissues were not involved. Culture zahlreiche septierte Hyphen als Ausdruck einer plates inoculated with pus and skin from the punch Hyalohyphomykose, die Subkutis war unauffa¨llig. biopsy showed growth of a mould yielding Im Kulturversuch mit bioptischem Material entwi- Pseudallescheria boydii. Sensitivity testing was per- ckelte sich wiederholte Male ein rasch wachsender formed with miconazole, ketoconazole and itra- Schimmelpilz, Pseudallescheria boydii. Gema¨ß der im conazole showing the best in vitro activity against Antimykogramm niedrigen Hemmkonzentration P. boydii. In spite of treatment with itraconazole, von Azolen wurde eine orale Therapie mit the erythema and pustules continued to spread Itraconazol eingeleitet, die Behandlung jedoch and therapy was changed to intravenous micona- wegen Progredienz der La¨sion auf intraveno¨ses zole. Due to ongoing progression after 3 months Miconazol umgestellt. Weiteres therapierefrakta¨res of antifungal therapy surgical debridement was Verhalten veranlasste nach 3-monatiger antimyze- required. After 2 years of follow up, he had no tischer Therapie das chirurgische Debridement recurrence. der kutanen Infektion. Der Patient pra¨sentiert sich bis heute ru¨ckfall- und erscheinungsfrei. 1Department of Dermatology, 2Division of Surgery, Department of Transplantation, University of Graz, Austria, and 3Centraalbureau voor Schimmelcultures, Baarn, The Introduction Netherlands. Fungal infection has emerged as a leading cause Correspondence: Prof. Dr Gabriele Ginter, Universita¨tsklinik fu¨r Dermatologie, Auenbruggerplatz 8, A-8036 Graz, Austria. of death among immunosuppressed and cancer Tel.: ++43/316 385 2371; Fax: ++43/316 385 2466 patients. Whereas Candida spp., Aspergillus spp. and 508 G. Ginter et al. Cryptococcus neoformans are common opportunistic fungal organisms causing infections in compro- mised hosts, Pseudallescheria boydii has emerged as an infrequently appearing pathogen that may become more frequent and threatening in the future [1]. Pseudallescheria boydii (Petriellidium boydii, Allescheria boydii) is an ubiquitous soil-inhabiting fungus that can be recovered from polluted water and sewage. Human infection can follow traumatic implant- ation or aspiration of contaminated water. Pseudallescheria boydii is the most frequent cause of fungal mycetoma in temperate regions. This chronic infection results from the traumatic implantation of the fungus into subcutaneous tissue [2]. Sinus tract formation with discharge of grains and spreading into adjacent tissue and bone are typical findings. The lung is the second most common site of P. boydii infection in humans with development of abscess formation or necrotizing pneumonia in immunosuppressed patients [3]. Fatal dissemi- nation may develop with infection of the central nervous system, meningitis, endocarditis, arthritis, osteomyelitis, soft tissue abscesses, kidney and eye infections [4]. Case report Figure 1. Pseudallescheriosis. Development of painless widespread miliary, partial pustular skin lesions with erythematous margins on the left forearm. The patient described here was a 65-year-old man with a history of severe dilating cardiopathy; for this reason he was treated with heart transplan- tation in March 1996. The patient was immuno- compromised secondary to cyclosporin, pred- nisolone and azathioprine but otherwise in good condition. Three months after transplantation, painless widespread miliary, partial pustular skin lesions with erythematous margins developed on his left forearm to the extent of about 8 cm×12 cm (Fig. 1). There was no history of trauma or septic temperature. Radiographic examination of the affected part revealed no bone involvement. When the patient was admitted to our clinic microbiological investigations were carried out: Figure 2. Histopathological examination (12×) of an excisional bacterial cultures were sterile and mycological biopsy from the left forearm revealed several granulomas within the investigation studies, i.e. potassium hydroxide upper dermis. There was no involvement of the subcutaneous fat. preparation and fungal culture of the skin were performed and yielded negative results. layer probably representing the remnant of a To establish a diagnosis a punch biopsy was dilated follicular infundibulum. The granulomas obtained on the left forearm lesion and the speci- consisted of a peripheral rim of epithelioid cells men was bisected for histopathological examin- intermingled with some multinuclear giant cells ation and repeated cultivation. Histopathological and a large central core with masses of neutrophils evaluation revealed several granulomas within the and nuclear dust (Fig. 3). Within this central upper dermis (Fig. 2). Remarkably, one of these abscess formation numerous septate hyphae, granulomas was surrounded by a thin epithelial 2–7 mm in diameter could already be easily mycoses 42, 507–511 (1999) Pseudallescheria boydii infection 509 Mc.Ginnis et al.(Graphium synanamorph) and con- firmed by de Hoog and Samson at CBS, Baarn. Sensitivity testing was performed by F. Odds from Janssen Research Foundation in Belgium with miconazole, ketoconazole and itraconazole showing best in vitro activity against Pseudallescheria boydii (Table 1). Treatment In accordance with the sensitivity testing values which showed the best in vitro activity with azoles, Figure 3. Histopathological examination (100×): The granulomas systemic treatment with itraconazole (200 mg p.o. consisted of a peripheral rim of epithelioid cells interminged with daily) was initiated first and an initial improvement some multinuclear giant cells and a large central core with masses of seemed to occur. However, after 8 weeks and in neutrophils and nuclear dust. spite of the treatment, the erythema and pustules were spreading and so itraconazole was changed to miconazole (600–1800 mg i.v. daily). detected with HE-stain (Fig. 4). These septate hyphae were found in a very large number especi- Due to ongoing progression—culture growth remained positive all the time (Table 2)—after ally within the epithelial cyst. There was no involvement of the subcutaneous fat. 3 months of therapy surgical debridement was required with the removal of at least 1.5 cm in These histopathological findings could be stated diameter of healthy tissue (Fig. 5). as dermal absceding granulomas with numerous septate hyphae resembling hyalohyphomycosis [5]. After 2 years of follow up, he had no recurrence. Culture plates (Sabouraud glucose agar, SGA) inoculated with pus and skin from the punch biopsy showed a rapid growth of a mould 3 days Conclusion after inoculation with colonies maturing within In patients undergoing immunosuppression due to 7 days. The colonies were fluffy, initially whitish, and later on mousehair grey to brownish in colour. cancer chemotherapy or organ transplant a high The reverse was white to grey, and finally black. Microscopic examination of the mycelial colon- Table 1. Pseudallescheria boydii: sensitivity testing* with ies showed characteristic hyaline branching septate miconazole, ketoconazole and itraconazole showing best hyphae with one-celled pale brown ovoid conidia in vitro activity. (*With request to F. C. Odds, PhD, MRC developing either singly or in clusters on short Path, JANSSEN Research Foundation) conidiophores. These findings were compatible MIC mg/ml with identification of Pseudallescheria boydii (Shear) Amphotericin B >8 Flucytosine >64 Fluconazole 4 Ketoconazole 0.25 Itraconazole 0.50 Miconazole 0.063 Terbinafine >16 Table 2. Growth of Pseudallescheria boydii in spite of treat- ment with itraconazole and miconazole for a 3-month period Date Therapy 10/07/96 positive Itraconazole 200 mg/day
Load more

Recommended publications
  • Cryptococcus Neoformans</Em>
    Clemson University TigerPrints All Dissertations Dissertations December 2019 Role of Cryptococcus neoformans Pyruvate Decarboxylase and Aldehyde Dehydrogenase Enzymes in Acetate Production and Virulence Mufida Ahmed Nagi Ammar Clemson University, [email protected] Follow this and additional works at: https://tigerprints.clemson.edu/all_dissertations Recommended Citation Ammar, Mufida Ahmed Nagi, "Role of Cryptococcus neoformans Pyruvate Decarboxylase and Aldehyde Dehydrogenase Enzymes in Acetate Production and Virulence" (2019). All Dissertations. 2488. https://tigerprints.clemson.edu/all_dissertations/2488 This Dissertation is brought to you for free and open access by the Dissertations at TigerPrints. It has been accepted for inclusion in All Dissertations by an authorized administrator of TigerPrints. For more information, please contact [email protected]. Role of Cryptococcus neoformans Pyruvate Decarboxylase and Aldehyde Dehydrogenase Enzymes in Acetate Production and Virulence A Dissertation Presented to the Graduate School of Clemson University In Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy Biochemistry and Molecular Biology by Mufida Ahmed Nagi Ammar December 2019 Accepted by: Dr. Kerry Smith, Committee Chair Dr. Julia Frugoli Dr. Cheryl Ingram-Smith Dr. Lukasz Kozubowski ABSTRACT The basidiomycete Cryptococcus neoformans is is an invasive opportunistic pathogen of the central nervous system and the most frequent cause of fungal meningitis. C. neoformans enters the host by inhalation and protects itself from immune assault in the lungs by producing hydrolytic enzymes, immunosuppressants, and other virulence factors. C. neoformans also adapts to the environment inside the host, including producing metabolites that may confer survival advantages. One of these, acetate, can be kept in reserve as a carbon source or can be used to weaken the immune response by lowering local pH or as a key part of immunomodulatory molecules.
    [Show full text]
  • Safety Precautions for Working with Cryptococcus Neoformans
    Safety Precautions for Working with Cryptococcus neoformans The basidiomycete fungus Cryptococcus neoformans is an invasive opportunistic pathogen of the central nervous system and the most frequent cause of fungal meningitis worldwide. Although Cryptococcus is a problem in the United States, it is significantly more prevalent and especially devastating in the developing world, such as sub-Saharan Africa, resulting in in more than 625,000 deaths per year worldwide. C. neoformans survives in the environment within soil, trees, and bird guano, where it can interact with wild animals or microbial predators, maintaining its virulence. Human infection is thought to be acquired by inhalation of desiccated yeast cells or spores from an environmental source. C. neoformans can colonize the host respiratory tract without producing any disease. Infection is typically asymptomatic, and it can be either cleared or enter a dormant, latent form. When host immunity is compromised, the dormant form can be reactivated and disseminate hematogenously to cause systemic infection. C. neoformans can infect or spread to any organ to cause localized infections involving the skin, eyes, myocardium, bones, joints, lungs, prostate gland, or urinary tract, in addition to its propensity to infect the central nervous systems. The following diseases and medications are risk factors for C. neoformans infection and are associated with at least some degree of immunosuppression: Ø HIV/AIDs (CD4 < 100cells/mm) Ø Corticosteroids or other immunosuppressive medications for cancer, chemotherapy, or organ transplants Ø Solid organ transplantations Ø Diabetes mellitus Ø Heart, lung, or liver disease Ø Pregnancy Even otherwise healthy, fully immunocompetent individuals can develop cryptococcosis, as may well be the case in a lab accident.
    [Show full text]
  • Chronic Mucocutaneous Candidiasis Associated with Paracoccidioidomycosis in a Patient with Mannose Receptor Deficiency: First Case Reported in the Literature
    Revista da Sociedade Brasileira de Medicina Tropical Journal of the Brazilian Society of Tropical Medicine Vol.:54:(e0008-2021): 2021 https://doi.org/10.1590/0037-8682-0008-2021 Case Report Chronic mucocutaneous candidiasis associated with paracoccidioidomycosis in a patient with mannose receptor deficiency: First case reported in the literature Dewton de Moraes Vasconcelos[1], Dalton Luís Bertolini[1] and Maurício Domingues Ferreira[1] [1]. Universidade de São Paulo, Faculdade de Medicina, Hospital das Clinicas, Departamento de Dermatologia, Ambulatório das Manifestações Cutâneas das Imunodeficiências Primárias, São Paulo, SP, Brasil. Abstract We describe the first report of a patient with chronic mucocutaneous candidiasis associated with disseminated and recurrent paracoccidioidomycosis. The investigation demonstrated that the patient had a mannose receptor deficiency, which would explain the patient’s susceptibility to chronic infection by Candida spp. and systemic infection by paracoccidioidomycosis. Mannose receptors are responsible for an important link between macrophages and fungal cells during phagocytosis. Deficiency of this receptor could explain the susceptibility to both fungal species, suggesting the impediment of the phagocytosis of these fungi in our patient. Keywords: Chronic mucocutaneous candidiasis. Paracoccidioidomycosis. Mannose receptor deficiency. INTRODUCTION “chronic mucocutaneous candidiasis and mannose receptor deficiency,” “chronic mucocutaneous candidiasis and paracoccidioidomycosis,” Chronic mucocutaneous
    [Show full text]
  • Identification of Culture-Negative Fungi in Blood and Respiratory Samples
    IDENTIFICATION OF CULTURE-NEGATIVE FUNGI IN BLOOD AND RESPIRATORY SAMPLES Farida P. Sidiq A Dissertation Submitted to the Graduate College of Bowling Green State University in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY May 2014 Committee: Scott O. Rogers, Advisor W. Robert Midden Graduate Faculty Representative George Bullerjahn Raymond Larsen Vipaporn Phuntumart © 2014 Farida P. Sidiq All Rights Reserved iii ABSTRACT Scott O. Rogers, Advisor Fungi were identified as early as the 1800’s as potential human pathogens, and have since been shown as being capable of causing disease in both immunocompetent and immunocompromised people. Clinical diagnosis of fungal infections has largely relied upon traditional microbiological culture techniques and examination of positive cultures and histopathological specimens utilizing microscopy. The first has been shown to be highly insensitive and prone to result in frequent false negatives. This is complicated by atypical phenotypes and organisms that are morphologically indistinguishable in tissues. Delays in diagnosis of fungal infections and inaccurate identification of infectious organisms contribute to increased morbidity and mortality in immunocompromised patients who exhibit increased vulnerability to opportunistic infection by normally nonpathogenic fungi. In this study we have retrospectively examined one-hundred culture negative whole blood samples and one-hundred culture negative respiratory samples obtained from the clinical microbiology lab at the University of Michigan Hospital in Ann Arbor, MI. Samples were obtained from randomized, heterogeneous patient populations collected between 2005 and 2006. Specimens were tested utilizing cetyltrimethylammonium bromide (CTAB) DNA extraction and polymerase chain reaction amplification of internal transcribed spacer (ITS) regions of ribosomal DNA utilizing panfungal ITS primers.
    [Show full text]
  • Pulmonary Cryptococcosis Secondary To
    & My gy co lo lo ro g i y V Ramana et al., Virol Mycol 2012, 1:3 Virology & Mycology DOI: 10.4172/2161-0517.1000107 ISSN: 2161-0517 Case Report Open Access Pulmonary Cryptococcosis Secondary to Bronchial Asthma Presenting as Type I Respiratory Failure- A Case Report with Review of Literature KV Ramana*, Moses Vinay Kumar, Sanjeev D Rao, Akhila R, Sandhya, Shruthi P, Pranuthi M, Krishnappa M, Anand K Department of Microbiology, Prathima Inst of Medical Sciences, Nagunur, Karimnagar, Andhrapradesh, India Introduction mellitus, pleuritis, systemic lupus erythematus, cushings syndrome, Continous Ambulatory Peritoneal Dialysis (CAPD), liver cirrhosis, Cryptococcus spp, was first isolated and described in 1894 by cancer, organ transplants, spleenectomy, malnutrition, leprosy, Sanfelice F in Italy from peach juice and named it as Saccharomyces pulmonary tuberculosis and those on cortico steroid therapy [13-20]. neoformans, is an yeast like fungus [1], first isolated from a clinical Pulmonary Cryptococcosis may be presenting as pleural effusions, specimen by Busse in the same year from Germany [2]. Cryptococci solitary or multiple masses, glass-ground interstitial opacities, dense are a saprophytic fungi present in soil contaminated with bird consolidations, patchy, segmented or lobar air space consolidation droppings mainly of pigeons, roosting sites and decaying vegetables (cryptococcal pneumonia) and nodular and reticulonodular cavities. [3]. Previous reports have also showed the presence of Cryptococcus Differential diagnosis of pulmonary cryptococcosis should be done spp colonized in the nasopharynx and on skin of healthy individuals with pneumonia [21,22]. Review of literature showed only two previous [4]. Belonging to Basidiomyctes group of fungi Cryptococcus spp reported cases of pulmonary cryptococcosis presenting as acute primarily infects central nervous system causing meningoencephalitis respiratory failure [7,23,24].
    [Show full text]
  • Environmental Factors That Contribute to the Maintenance of Cryptococcus Neoformans Pathogenesis
    microorganisms Review Environmental Factors That Contribute to the Maintenance of Cryptococcus neoformans Pathogenesis Maphori Maliehe, Mathope A. Ntoi, Shayanki Lahiri, Olufemi S. Folorunso , Adepemi O. Ogundeji , Carolina H. Pohl and Olihile M. Sebolai * Department of Microbial, Biochemical and Food Biotechnology, University of the Free State, Bloemfontein 9301, Free State, South Africa; [email protected] (M.M.); [email protected] (M.A.N.); [email protected] (S.L.); [email protected] (O.S.F.); [email protected] (A.O.O.); [email protected] (C.H.P.) * Correspondence: [email protected]; Tel.: +27-(0)51-401-2004 Received: 15 November 2019; Accepted: 11 December 2019; Published: 28 January 2020 Abstract: The ability of microorganisms to colonise and display an intracellular lifestyle within a host body increases their fitness to survive and avoid extinction. This host–pathogen association drives microbial evolution, as such organisms are under selective pressure and can become more pathogenic. Some of these microorganisms can quickly spread through the environment via transmission. The non-transmittable fungal pathogens, such as Cryptococcus, probably return into the environment upon decomposition of the infected host. This review analyses whether re-entry of the pathogen into the environment causes restoration of its non-pathogenic state or whether environmental factors and parameters assist them in maintaining pathogenesis. Cryptococcus (C.) neoformans is therefore used as a model organism to evaluate the impact of environmental stress factors that aid the survival and pathogenesis of C. neoformans intracellularly and extracellularly. Keywords: Cryptococcus; environmental factors; pathogenesis; survival; virulence factors; transcriptional factors; signalling factors 1. Introduction The genus Cryptococcus is defined by basidiomycetous fungi that can transform into a yeast state [1].
    [Show full text]
  • Laboratory Manual for Diagnosis of Fungal Opportunistic Infections in HIV/AIDS Patients
    The human immunodeficiency virus per se does not kill the infected individuals. Instead, it weakens the body's ability to fight disease. Infections which are rarely seen in those with normal immune systems can be deadly to those with HIV. People with HIV can get many infections (known as opportunistic infections, or OIs). Many of these illnesses are very serious and require treatment. Some can be prevented. Of the several OIs that cause morbidity and mortality in HIV infected individuals those belonging to various genera of fungi have assumed great importance in recent past. Since these OIs were earlier considered as nonpathogenic, the diagnostic services for confirmation of their causative role need to be strengthened. This document is an endeavour in this direction and hopefully shall be useful in establishing early diagnosis of fungal OIs in HIV infected people thus assuring rapid institution of specific treatment. Laboratory manual for diagnosis of fungal opportunistic infections World Health House Indraprastha Estate, in HIV/AIDS patients Mahatma Gandhi Marg, New Delhi-110002, India Website: www.searo.who.int SEA-HLM-401 SEA-HLM-401 Distribution: General Laboratory manual for diagnosis of fungal opportunistic infections in HIV/AIDS patients Regional Office for South-East Asia © World Health Organization 2009 All rights reserved. Requests for publications, or for permission to reproduce or translate WHO publications – whether for sale or for noncommercial distribution – can be obtained from Publishing and Sales, World Health Organization, Regional Office for South-East Asia, Indraprastha Estate, Mahatma Gandhi Marg, New Delhi 110 002, India (fax: +91 11 23370197; e-mail: [email protected]).
    [Show full text]
  • Kwon-Chung Et Al (2014)
    Downloaded from http://perspectivesinmedicine.cshlp.org/ at The University of Manchester Library on July 5, 2018 - Published by Cold Spring Harbor Laboratory Press Cryptococcus neoformans and Cryptococcus gattii, the Etiologic Agents of Cryptococcosis Kyung J. Kwon-Chung1, James A. Fraser2, Tamara L. Doering3, Zhuo A. Wang3, Guilhem Janbon4, Alexander Idnurm5, and Yong-Sun Bahn6 1Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892 2Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, Queensland 4072, Australia 3Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110 4Unite´ Biologie et Pathoge´nicite´ Fongiques, Institut Pasteur, 75015 Paris, France 5Division of Cell Biology and Biophysics, School of Biological Sciences, University of Missouri, Kansas City, Missouri 64110 6Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 120–749, Republic of Korea Correspondence: [email protected] Cryptococcus neoformans and Cryptococcus gattii are the two etiologic agents of crypto- coccosis. They belong to the phylum Basidiomycota and can be readily distinguished from other pathogenic yeasts such as Candida by the presence of a polysaccharide capsule, formation of melanin, and urease activity, which all function as virulence determinants. Infection proceeds via inhalation and subsequent dissemination to the central nervous
    [Show full text]
  • The Evolution of Cryptococcus Neoformans Var. Grubii in the Context of Clinical Disease Using Multilocus Sequence Typing
    Imperial College London School of Public Health The evolution of Cryptococcus neoformans var. grubii in the context of clinical disease using multilocus sequence typing Sitali P. Simwami September 2011 Submitted in part fulfilment of the requirements for the degree of Doctor of Philosophy in the School of Public Health of Imperial College London and the Diploma of Imperial College London Declaration I herewith certify that all material in this dissertation which is not my own work has been properly acknowledged. Sitali P. Simwami 3 Abstract The global burden of HIV-associated cryptococcal meningitis (CM) is es- timated at one million cases per year, causing up to a third of all AIDS- related deaths. Cryptococcus neoformans variety grubii (Cng) is the most ubiquitous cause of cryptococcal meningitis worldwide, however patterns of molecular diversity are understudied across some geographical regions ex- periencing significant burdens of disease. Cryptococcus species are notable in the degree that virulence differs amongst lineages, and highly virulent emerging lineages are changing patterns of human disease both temporally and spatially. Molecular epidemiology constitutes the main methodology for understanding the factors underpinning the emergence of this under- studied, yet increasingly important, group of pathogenic fungi. A multilo- cus sequence typing (MLST) scheme was used to characterise a genetically depauperate Cng population in Thailand, and a contrastingly highly di- verse Cng population in Cape Town, South Africa. Sequence types (STs) from these populations were integrated into a dataset comprising global STs of Cng and patterns of range expansion were traced. Evidence from haplotypic networks and coalescent analyses revealed an ancestral African population of molecular type VNB, from which emerged a VNI lineage.
    [Show full text]
  • Biology, Systematics and Clinical Manifestations of Zygomycota Infections
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by IBB PAS Repository Biology, systematics and clinical manifestations of Zygomycota infections Anna Muszewska*1, Julia Pawlowska2 and Paweł Krzyściak3 1 Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawiskiego 5a, 02-106 Warsaw, Poland; [email protected], [email protected], tel.: +48 22 659 70 72, +48 22 592 57 61, fax: +48 22 592 21 90 2 Department of Plant Systematics and Geography, University of Warsaw, Al. Ujazdowskie 4, 00-478 Warsaw, Poland 3 Department of Mycology Chair of Microbiology Jagiellonian University Medical College 18 Czysta Str, PL 31-121 Krakow, Poland * to whom correspondence should be addressed Abstract Fungi cause opportunistic, nosocomial, and community-acquired infections. Among fungal infections (mycoses) zygomycoses are exceptionally severe with mortality rate exceeding 50%. Immunocompromised hosts, transplant recipients, diabetic patients with uncontrolled keto-acidosis, high iron serum levels are at risk. Zygomycota are capable of infecting hosts immune to other filamentous fungi. The infection follows often a progressive pattern, with angioinvasion and metastases. Moreover, current antifungal therapy has often an unfavorable outcome. Zygomycota are resistant to some of the routinely used antifungals among them azoles (except posaconazole) and echinocandins. The typical treatment consists of surgical debridement of the infected tissues accompanied with amphotericin B administration. The latter has strong nephrotoxic side effects which make it not suitable for prophylaxis. Delayed administration of amphotericin and excision of mycelium containing tissues worsens survival prognoses. More than 30 species of Zygomycota are involved in human infections, among them Mucorales are the most abundant.
    [Show full text]
  • Inositol Polyphosphate Kinases, Fungal Virulence and Drug Discovery
    Journal of Fungi Review Inositol Polyphosphate Kinases, Fungal Virulence and Drug Discovery Cecilia Li 1, Sophie Lev 1, Adolfo Saiardi 2, Desmarini Desmarini 1, Tania C. Sorrell 1,3,4 and Julianne T. Djordjevic 1,3,4,* 1 Centre for Infectious Diseases and Microbiology, The Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145, Australia; [email protected] (C.L.); [email protected] (S.L.); [email protected] (D.D.); [email protected] (T.C.S.) 2 Medical Research Council Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UK; [email protected] 3 Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, Westmead, NSW 2145, Australia 4 Westmead Hospital, Westmead, NSW 2145, Australia * Correspondence: [email protected]; Tel.: +61-2-8627-3420 Academic Editor: Maurizio Del Poeta Received: 22 July 2016; Accepted: 30 August 2016; Published: 6 September 2016 Abstract: Opportunistic fungi are a major cause of morbidity and mortality world-wide, particularly in immunocompromised individuals. Developing new treatments to combat invasive fungal disease is challenging given that fungal and mammalian host cells are eukaryotic, with similar organization and physiology. Even therapies targeting unique fungal cell features have limitations and drug resistance is emerging. New approaches to the development of antifungal drugs are therefore needed urgently. Cryptococcus neoformans, the commonest cause of fungal meningitis worldwide, is an accepted model for studying fungal pathogenicity and driving drug discovery. We recently characterized a phospholipase C (Plc1)-dependent pathway in C. neoformans comprising of sequentially-acting inositol polyphosphate kinases (IPK), which are involved in synthesizing inositol polyphosphates (IP).
    [Show full text]
  • Multiple GAL Pathway Gene Clusters Evolved Independently and by Different Mechanisms in Fungi
    Multiple GAL pathway gene clusters evolved independently and by different mechanisms in fungi Jason C. Slot and Antonis Rokas1 Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235 Edited* by John Doebley, University of Wisconsin, Madison, WI, and approved April 23, 2010 (received for review December 14, 2009) A notable characteristic of fungal genomes is that genes involved in 4-epimerase) domain, but not in other fungal lineages. In the successive steps of a metabolic pathway are often physically linked second step, α-D-galactose is phosphorylated into α-D-galactose- or clustered. To investigate how such clusters of functionally related 1-phosphate by Gal1p (galactokinase), whereas in the third step, genes are assembled and maintained, we examined the evolution of UDP is transferred from UDP-α-D-glucose-1-phosphate to α-D- gene sequences and order in the galactose utilization (GAL)pathway galactose-1-phosphate via Gal7p (galactose-1-phosphate uridylyl in whole-genome data from 80 diverse fungi. We found that GAL transferase), thereby freeing glucose-1-phosphate. In the fourth gene clusters originated independently and by different mechanisms and final step, UDP-α-D-galactose-1-phosphate is used to regen- in three unrelated yeast lineages. Specifically, the GAL cluster found erate UDP-α-D-glucose-1-phosphate by the epimerase domain in Saccharomyces and Candida yeasts originated through the reloca- of Gal10p. tion of native unclustered genes, whereas the GAL cluster of Schiz- Whereas GAL1, GAL7, and GAL10 are unclustered in most osaccharomyces yeasts was acquired through horizontal gene trans- fungi (23–27), they are clustered in S.
    [Show full text]