J. Fungi2016, 2(2), 16; doi:10.3390/jof2020016 (registering DOI) - published 28 May 2016 Show/Hide Abstract
Abstract: Non-pneumonia Pneumocystis jirovecii colonization is thought to occur frequently in immunocompetent individuals. The aim was to analyze if P. jirovecii low-titer detections have more impact than just colonization. From our total cohort of patients for which P. jirovecii testing by qPCR was requested, we selected exclusively those that were fully immunocompetent. Patients were defined as fully immunocompetent if they did not receive immunosuppressive therapy, displayed regular antibody titers, and did not suffer from acquired, inherited or autoimmune diseases. Only those patients with complete medical records available were included. A retrospective analysis identified patients with P. jirovecii colonization and successful antibiotic therapy in response to laboratory pathogen detection. We identified 30 fully immunocompetent patients with P. jirovecii colonization suspected to suffer from infection with the pathogen, but with milder symptoms than pneumonia. All patients were successfully treated with cotrimoxazole against P. jirovecii and resolved from chronic cough and recurrent pulmonary infections. The fact that all patients displayed recovery from their clinical symptoms gives raise to the hypothesis that P. jirovecii infections may also occur in immunocompetent patients but with milder symptoms.
Abstract: Patients with chronic granulomatous disease (CGD) have the highest life-time incidence of invasive aspergillosis and despite the availability of antifungal prophylaxis, infections by Aspergillus species remain the single most common infectious cause of death in CGD. Recent developments in curative treatment options, such as haematopoietic stem cell transplantation, will change the prevalence of infectious complications including invasive aspergillosis in CGD patients. However, invasive aspergillosis in a previously healthy host is often the first presenting feature of this primary immunodeficiency. Recognizing the characteristic clinical presentation and understanding how to diagnose and treat invasive aspergillosis in CGD is of utmost relevance to improve clinical outcomes. Significant differences exist in fungal epidemiology, clinical signs and symptoms, and the usefulness of non-culture based diagnostic tools between the CGD host and neutropenic patients, reflecting underlying differences in the pathogenesis of invasive aspergillosis shaped by the nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase deficiency.
Abstract: AIDS-related cryptococcal meningitis continues to cause a substantial burden of death in low and middle income countries. Better diagnostics allow detection of cryptococcosis in the asymptomatic phase and using these technologies to screen at-risk persons would likely reduce mortality. The World Health Organization recommends cryptococcal antigen screening among populations with a prevalence of cryptococcal antigenaemia (CRAG) > 3%. There is scarce data about CRAG prevalence in Latin America. Four studies (only one published as a full text) showed asymptomatic CRAG prevalence between 2.7% and 6.2% in several sub-sets of HIV-infected patients. The CRAG lateral flow assay (LFA) has several advantages over other techniques for actual implementation of a screening program. Although more studies are necessary to confirm available data, implementation of the CRAG screening strategy seems to be opportune in Latin America.
J. Fungi2016, 2(2), 13; doi:10.3390/jof2020013 - published 30 April 2016 Show/Hide Abstract
Abstract: The fungus Aspergillus (A.) terreus has dominated the biological production of the “blockbuster” drugs known as statins. The statins are a class of drugs that inhibit HMG-CoA reductase and lead to lower cholesterol production. The statins were initially discovered in fungi and for many years fungi were the sole source for the statins. At present, novel chemically synthesised statins are produced as inspired by the naturally occurring statin molecules. The isolation of the natural statins, compactin, mevastatin and lovastatin from A. terreus represents one of the great achievements of industrial microbiology. Here we review the discovery of statins, along with strategies that have been applied to scale up their production by A. terreus strains. The strategies encompass many of the techniques available in industrial microbiology and include the optimization of media and fermentation conditions, the improvement of strains through classical mutagenesis, induced genetic manipulation and the use of statistical design.
J. Fungi2016, 2(2), 12; doi:10.3390/jof2020012 - published 19 April 2016 Show/Hide Abstract
Abstract: Fungal pure cultures identified with both classical morphological methods and through barcoding sequences are a basic requirement for reliable reference sequences in public databases. Improved techniques for an accelerated DNA barcode reference library construction will result in considerably improved sequence databases covering a wider taxonomic range. Fast, cheap, and reliable methods for obtaining DNA sequences from fungal isolates are, therefore, a valuable tool for the scientific community. Direct colony PCR was already successfully established for yeasts, but has not been evaluated for a wide range of anamorphic soil fungi up to now, and a direct amplification protocol for hyphomycetes without tissue pre-treatment has not been published so far. Here, we present a colony PCR technique directly from fungal hyphae without previous DNA extraction or other prior manipulation. Seven hundred eighty-eight fungal strains from 48 genera were tested with a success rate of 86%. PCR success varied considerably: DNA of fungi belonging to the genera Cladosporium, Geomyces, Fusarium, and Mortierella could be amplified with high success. DNA of soil-borne yeasts was always successfully amplified. Absidia, Mucor, Trichoderma, and Penicillium isolates had noticeably lower PCR success.
J. Fungi2016, 2(1), 11; doi:10.3390/jof2010011 - published 3 March 2016 Show/Hide Abstract
Abstract: Chitosan is a biopolymer with a wide range of applications. The use of chitosan in clinical medicine to control infections by fungal pathogens such as Candida spp. is one of its most promising applications in view of the reduced number of antifungals available. Chitosan increases intracellular oxidative stress, then permeabilizes the plasma membrane of sensitive filamentous fungus Neurospora crassa and yeast. Transcriptomics reveals plasma membrane homeostasis and oxidative metabolism genes as key players in the response of fungi to chitosan. A lipase and a monosaccharide transporter, both inner plasma membrane proteins, and a glutathione transferase are main chitosan targets in N. crassa. Biocontrol fungi such as Pochonia chlamydosporia have a low content of polyunsaturated free fatty acids in their plasma membranes and are resistant to chitosan. Genome sequencing of P. chlamydosporia reveals a wide gene machinery to degrade and assimilate chitosan. Chitosan increases P. chlamydosporia sporulation and enhances parasitism of plant parasitic nematodes by the fungus. Omics studies allow understanding the mode of action of chitosan and help its development as an antifungal and gene modulator.