Journal of Fungi

Editorial

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5 pages, 191 KiB

Open AccessEditorial

Special Issue: Mucorales and Mucormycosis

by Eric Dannaoui and Michaela Lackner

J. Fungi 2020, 6(1), 6; https://0-doi-org.brum.beds.ac.uk/10.3390/jof6010006 - 23 Dec 2019

Cited by 6 | Viewed by 3519

Abstract

Mucormycosis is a life-threatening infection, occurring mainly in immunocompromised patients, but also in immunocompetent patients after traumatic injuries [...] Full article

(This article belongs to the Special Issue Mucorales and Mucormycosis)

Research

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11 pages, 898 KiB

Open AccessArticle

Identification of Mucorales by Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry

by Patrick Schwarz, Houssem Guedouar, Farah Laouiti, Frédéric Grenouillet and Eric Dannaoui

J. Fungi 2019, 5(3), 56; https://0-doi-org.brum.beds.ac.uk/10.3390/jof5030056 - 02 Jul 2019

Cited by 16 | Viewed by 3634

Abstract

More than 20 different species of Mucorales can be responsible for human mucormycosis. Accurate identification to the species level is important. The morphological identification of Mucorales is not reliable, and the currently recommended identification standard is the molecular technique of sequencing the internal [...] Read more.

More than 20 different species of Mucorales can be responsible for human mucormycosis. Accurate identification to the species level is important. The morphological identification of Mucorales is not reliable, and the currently recommended identification standard is the molecular technique of sequencing the internal transcribed spacer regions. Nevertheless, matrix-assisted laser desorption ionization time-of-flight mass spectrometry has been shown to be an accurate alternative for the identification of bacteria, yeasts, and even filamentous fungi. Therefore, 38 Mucorales isolates, belonging to 12 different species or varieties, mainly from international collections, including 10 type or neo-type strains previously identified by molecular methods, were used to evaluate the usefulness of matrix-assisted laser desorption ionization time-of-flight mass spectrometry for the identification of human pathogenic Mucorales to the species level. One to three reference strains for each species were used to create a database of main spectrum profiles, and the remaining isolates were used as test isolates. A minimum of 10 spectra was used to build the main spectrum profile of each database strain. Interspecies discrimination for all the isolates, including species belonging to the same genus, was possible. Twenty isolates belonging to five species were used to test the database accuracy, and were correctly identified to the species level with a log-score >2. In summary, matrix-assisted laser desorption ionization time-of-flight mass spectrometry is a reliable and rapid method for the identification of most of the human pathogenic Mucorales to the species level. Full article

(This article belongs to the Special Issue Mucorales and Mucormycosis)

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12 pages, 2450 KiB

Open AccessArticle

In Vitro and In Vivo Evaluation of Voriconazole-Containing Antifungal Combinations against Mucorales Using a Galleria mellonella Model of Mucormycosis

by Daiana Macedo, Florencia Leonardelli, Catiana Dudiuk, Roxana G. Vitale, Eleodoro Del Valle, Gustavo Giusiano, Soledad Gamarra and Guillermo Garcia-Effron

J. Fungi 2019, 5(1), 5; https://0-doi-org.brum.beds.ac.uk/10.3390/jof5010005 - 08 Jan 2019

Cited by 11 | Viewed by 4016

Abstract

Mucorales are resistant to most antifungals. Mucormycosis associated mortality is unacceptable and new treatment approaches are needed. The objectives of this work were (i) to evaluate the nature and intensity of the in vitro effect of three drugs combinations which included voriconazole (plus [...] Read more.

Mucorales are resistant to most antifungals. Mucormycosis associated mortality is unacceptable and new treatment approaches are needed. The objectives of this work were (i) to evaluate the nature and intensity of the in vitro effect of three drugs combinations which included voriconazole (plus amphotericin B, posaconazole and caspofungin) against 25 strains of six different Mucorales species; (ii) to evaluate a Galleria mellonella mucormycosis model; and (iii) to establish if any in vitro–in vivo correlation exists. As expected, amphotericin B and posaconazole were the most active drugs when tested alone. However, species-specific differences were found. The ΣFICs varied according to the used combination. Only five strains showed synergism when voriconazole was combined with posaconazole and three strains when combined with amphotericin B. Microscopic hyphae alteration were observed for some isolates when confronted against drugs combinations. Using a Galleria mellonella mucormycosis model, better survival was seen in voriconazole plus amphotericin B and plus caspofungin combined treatments when compared with AMB alone for R. microsporus. These survival improvements were obtained using a 32-fold lower amphotericin B doses when combined with VRC than when treated with the polyene alone. These lower antifungal doses emulate the antifungal concentrations where the microscopic hyphae alterations were seen. Full article

(This article belongs to the Special Issue Mucorales and Mucormycosis)

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Review

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14 pages, 247 KiB

Open AccessReview

Biotic Environments Supporting the Persistence of Clinically Relevant Mucormycetes

by Malcolm D. Richardson and Riina Rautemaa-Richardson

J. Fungi 2020, 6(1), 4; https://0-doi-org.brum.beds.ac.uk/10.3390/jof6010004 - 20 Dec 2019

Cited by 24 | Viewed by 5255

Abstract

Clinically relevant members of the Mucorales group can grow and are found in diverse ecological spaces such as soil, dust, water, decomposing vegetation, on and in food, and in hospital environments but are poorly represented in mycobiome studies of outdoor and indoor air. [...] Read more.

Clinically relevant members of the Mucorales group can grow and are found in diverse ecological spaces such as soil, dust, water, decomposing vegetation, on and in food, and in hospital environments but are poorly represented in mycobiome studies of outdoor and indoor air. Occasionally, Mucorales are found in water-damaged buildings. This mini review examines a number of specialised biotic environments, including those revealed by natural disasters and theatres of war, that support the growth and persistence of these fungi. However, we are no further forward in understanding exposure pathways or the chronicity of exposure that results in the spectrum of clinical presentations of mucormycosis. Full article

(This article belongs to the Special Issue Mucorales and Mucormycosis)

23 pages, 1809 KiB

Open AccessReview

Updates on the Taxonomy of Mucorales with an Emphasis on Clinically Important Taxa

by Grit Walther, Lysett Wagner and Oliver Kurzai

J. Fungi 2019, 5(4), 106; https://0-doi-org.brum.beds.ac.uk/10.3390/jof5040106 - 14 Nov 2019

Cited by 116 | Viewed by 13877

Abstract

Fungi of the order Mucorales colonize all kinds of wet, organic materials and represent a permanent part of the human environment. They are economically important as fermenting agents of soybean products and producers of enzymes, but also as plant parasites and spoilage organisms. [...] Read more.

Fungi of the order Mucorales colonize all kinds of wet, organic materials and represent a permanent part of the human environment. They are economically important as fermenting agents of soybean products and producers of enzymes, but also as plant parasites and spoilage organisms. Several taxa cause life-threatening infections, predominantly in patients with impaired immunity. The order Mucorales has now been assigned to the phylum Mucoromycota and is comprised of 261 species in 55 genera. Of these accepted species, 38 have been reported to cause infections in humans, as a clinical entity known as mucormycosis. Due to molecular phylogenetic studies, the taxonomy of the order has changed widely during the last years. Characteristics such as homothallism, the shape of the suspensors, or the formation of sporangiola are shown to be not taxonomically relevant. Several genera including Absidia, Backusella, Circinella, Mucor, and Rhizomucor have been amended and their revisions are summarized in this review. Medically important species that have been affected by recent changes include Lichtheimia corymbifera, Mucor circinelloides, and Rhizopus microsporus. The species concept of Rhizopus arrhizus (syn. R. oryzae) is still a matter of debate. Currently, species identification of the Mucorales is best performed by sequencing of the internal transcribed spacer (ITS) region. Ecologically, the Mucorales represent a diverse group but for the majority of taxa, the ecological role and the geographic distribution remain unknown. Understanding the biology of these opportunistic fungal pathogens is a prerequisite for the prevention of infections, and, consequently, studies on the ecology of the Mucorales are urgently needed. Full article

(This article belongs to the Special Issue Mucorales and Mucormycosis)

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11 pages, 686 KiB

Open AccessReview

Necrotizing Mucormycosis of Wounds Following Combat Injuries, Natural Disasters, Burns, and Other Trauma

by Thomas J. Walsh, Duane R. Hospenthal, Vidmantas Petraitis and Dimitrios P. Kontoyiannis

J. Fungi 2019, 5(3), 57; https://0-doi-org.brum.beds.ac.uk/10.3390/jof5030057 - 04 Jul 2019

Cited by 34 | Viewed by 5399

Abstract

Necrotizing mucormycosis is a devastating complication of wounds incurred in the setting of military (combat) injuries, natural disasters, burns, or other civilian trauma. Apophysomyces species, Saksenaea species and Lichtheimia (formerly Absidia) species, although uncommon as causes of sinopulmonary mucormycosis, are relatively frequent agents [...] Read more.

Necrotizing mucormycosis is a devastating complication of wounds incurred in the setting of military (combat) injuries, natural disasters, burns, or other civilian trauma. Apophysomyces species, Saksenaea species and Lichtheimia (formerly Absidia) species, although uncommon as causes of sinopulmonary mucormycosis, are relatively frequent agents of trauma-related mucormycosis. The pathogenesis of these infections likely involves a complex interaction among organism, impaired innate host defenses, and biofilms related to traumatically implanted foreign materials. Effective management depends upon timely diagnosis, thorough surgical debridement, and early initiation of antifungal therapy. Full article

(This article belongs to the Special Issue Mucorales and Mucormycosis)

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22 pages, 286 KiB

Open AccessReview

Animal Models to Study Mucormycosis

by Ilse D. Jacobsen

J. Fungi 2019, 5(2), 27; https://0-doi-org.brum.beds.ac.uk/10.3390/jof5020027 - 27 Mar 2019

Cited by 21 | Viewed by 4712

Abstract

Mucormycosis is a rare but often fatal or debilitating infection caused by a diverse group of fungi. Animal models have been crucial in advancing our knowledge of mechanisms influencing the pathogenesis of mucormycoses, and to evaluate therapeutic strategies. This review describes the animal [...] Read more.

Mucormycosis is a rare but often fatal or debilitating infection caused by a diverse group of fungi. Animal models have been crucial in advancing our knowledge of mechanisms influencing the pathogenesis of mucormycoses, and to evaluate therapeutic strategies. This review describes the animal models established for mucormycosis, summarizes how they have been applied to study mucormycoses, and discusses the advantages and limitations of the different model systems. Full article

(This article belongs to the Special Issue Mucorales and Mucormycosis)

19 pages, 859 KiB

Open AccessReview

Global Epidemiology of Mucormycosis

by Hariprasath Prakash and Arunaloke Chakrabarti

J. Fungi 2019, 5(1), 26; https://0-doi-org.brum.beds.ac.uk/10.3390/jof5010026 - 21 Mar 2019

Cited by 502 | Viewed by 19686

Abstract

Mucormycosis is an angio-invasive fungal infection, associated with high morbidity and mortality. A change in the epidemiology of mucormycosis has been observed in recent years with the rise in incidence, new causative agents and susceptible population. The rise has been perceived globally, but [...] Read more.

Mucormycosis is an angio-invasive fungal infection, associated with high morbidity and mortality. A change in the epidemiology of mucormycosis has been observed in recent years with the rise in incidence, new causative agents and susceptible population. The rise has been perceived globally, but it is very high in the Asian continent. Though diabetes mellitus overshadow all other risk factors in Asia, post-tuberculosis and chronic renal failure have emerged as new risk groups. The rhino-cerebral form of mucormycosis is most commonly seen in patients with diabetes mellitus, whereas, pulmonary mucormycosis in patients with haematological malignancy and transplant recipients. In immunocompetent hosts, cutaneous mucormycosis is commonly seen following trauma. The intriguing clinical entity, isolated renal mucormycosis in immunocompetent patients is only reported from China and India. A new clinical entity, indolent mucormycosis in nasal sinuses, is recently recognized. The causative agents of mucormycosis vary across different geographic locations. Though Rhizopus arrhizus is the most common agent isolated worldwide, Apophysomyces variabilis is predominant in Asia and Lichtheimia species in Europe. The new causative agents, Rhizopus homothallicus, Mucor irregularis, and Thamnostylum lucknowense are reported from Asia. In conclusion, with the change in epidemiology of mucormycosis country-wise studies are warranted to estimate disease burden in different risk groups, analyse the clinical disease pattern and identify the new etiological agents. Full article

(This article belongs to the Special Issue Mucorales and Mucormycosis)

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12 pages, 241 KiB

Open AccessReview

Mucormycosis in Burn Patients

by Pauline Devauchelle, Mathieu Jeanne and Emilie Fréalle

J. Fungi 2019, 5(1), 25; https://0-doi-org.brum.beds.ac.uk/10.3390/jof5010025 - 21 Mar 2019

Cited by 22 | Viewed by 3928

Abstract

Patients with extensive burns are an important group at risk for cutaneous mucormycosis. This study aimed to perform a systematic review of all reported mucormycosis cases in burn patients from 1990 onward. A Medline search yielded identification of 7 case series, 3 outbreaks, [...] Read more.

Patients with extensive burns are an important group at risk for cutaneous mucormycosis. This study aimed to perform a systematic review of all reported mucormycosis cases in burn patients from 1990 onward. A Medline search yielded identification of 7 case series, 3 outbreaks, and 25 individual cases reports. The prevalence reached 0.04%–0.6%. The median age was 42–48 in the case series and outbreaks, except for the studies from military centers (23.5–32.5) and in individual reports (29.5). The median total body surface area reached 42.5%–65%. Various skin lesions were described, none being pathognomonic: the diagnosis was mainly reached because of extensive necrotic lesions sometimes associated with sepsis. Most patients were treated with systemic amphotericin B or liposomal amphotericin B, and all underwent debridement and/or amputation. Mortality reached 33%–100% in the case series, 29%–62% during outbreaks, and 40% in individual cases. Most patients were diagnosed using histopathology and/or culture. Mucorales qPCR showed detection of circulating DNA 2–24 days before the standard diagnosis. Species included the main clinically relevant mucorales (i.e., Mucor, Rhizopus, Absidia/Lichtheimia, Rhizomucor) but also more uncommon mucorales such as Saksenaea or Apophysomyces. Contact with soil was reported in most individual cases. Bandages were identified as the source of contamination in two nosocomial outbreaks. Full article

(This article belongs to the Special Issue Mucorales and Mucormycosis)

8 pages, 206 KiB

Open AccessReview

Molecular Strategies to Diagnose Mucormycosis

by Laurence Millon, Emeline Scherer, Steffi Rocchi and Anne-Pauline Bellanger

J. Fungi 2019, 5(1), 24; https://0-doi-org.brum.beds.ac.uk/10.3390/jof5010024 - 20 Mar 2019

Cited by 74 | Viewed by 5293

Abstract

Molecular techniques have provided a new understanding of the epidemiology of mucormycosis and improved the diagnosis and therapeutic management of this life-threatening disease. PCR amplification and sequencing were first applied to better identify isolates that were grown from cultures of biopsies or bronchalveolar [...] Read more.

Molecular techniques have provided a new understanding of the epidemiology of mucormycosis and improved the diagnosis and therapeutic management of this life-threatening disease. PCR amplification and sequencing were first applied to better identify isolates that were grown from cultures of biopsies or bronchalveolar lavage samples that were collected in patients with Mucorales infection. Subsequently, molecular techniques were used to identify the fungus directly from the infected tissues or from bronchalveolar lavage, and they helped to accurately identify Mucorales fungi in tissue samples when the cultures were negative. However, these tools require invasive sampling (biospsy, bronchalveolar lavage), which is not feasible in patients in poor condition in Hematology or Intensive Care units. Very recently, PCR-based procedures to detect Mucorales DNA in non-invasive samples, such as plasma or serum, have proved successful in diagnosing mucormycosis early in all patients, whatever the clinical status, and these procedures are becoming essential to improving patient outcome. Full article

(This article belongs to the Special Issue Mucorales and Mucormycosis)

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9 pages, 1882 KiB

Open AccessReview

Disease Entities in Mucormycosis

by Alexandra Serris, François Danion and Fanny Lanternier

J. Fungi 2019, 5(1), 23; https://0-doi-org.brum.beds.ac.uk/10.3390/jof5010023 - 14 Mar 2019

Cited by 89 | Viewed by 8546

Abstract

Mucormycosis is an emerging life-threatening fungal infection caused by Mucorales. This infection occurs mainly in immunocompromised patients, especially with hematological malignancy, transplantation, or diabetes mellitus. Rhino-orbito-cerebral and pulmonary mucormycosis are the predominant forms. Interestingly, location is associated with the underlying disease as [...] Read more.

Mucormycosis is an emerging life-threatening fungal infection caused by Mucorales. This infection occurs mainly in immunocompromised patients, especially with hematological malignancy, transplantation, or diabetes mellitus. Rhino-orbito-cerebral and pulmonary mucormycosis are the predominant forms. Interestingly, location is associated with the underlying disease as pulmonary mucormycosis is more frequent in hematological malignancy patients whereas rhino-orbito-cerebral mucormycosis is associated with diabetes. Cutaneous mucormycosis results from direct inoculation, mainly after trauma or surgery. Gastro-intestinal mucormycosis occurs after ingestion of contaminated food or with contaminated device and involves the stomach or colon. Disseminated disease is the most severe form and is associated with profound immunosuppression. Uncommon presentations with endocarditis, osteoarticluar or isolated cerebral infections are also described. Finally, health-care associated mucormycosis is a matter of concern in premature newborns and burn units. Clinical symptoms and CT scan findings are not specific, only the early reversed halo sign is associated with pulmonary mucormycosis. Circulating Mucorales DNA detection is a recent promising diagnostic tool that may lead to improving the diagnosis and prompting therapeutic initiation that should include antifungal treatment, correction of the underlying disease and surgery when feasible. Full article

(This article belongs to the Special Issue Mucorales and Mucormycosis)

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