Journal of Fungi

Research

20 pages, 780 KiB

Open AccessArticle

Selection of an Appropriate In Vitro Susceptibility Test for Assessing Anti-Pythium insidiosum Activity of Potassium Iodide, Triamcinolone Acetonide, Dimethyl Sulfoxide, and Ethanol

by Hanna Yolanda, Tassanee Lohnoo, Thidarat Rujirawat, Wanta Yingyong, Yothin Kumsang, Pattarana Sae-Chew, Penpan Payattikul and Theerapong Krajaejun

J. Fungi 2022, 8(11), 1116; https://doi.org/10.3390/jof8111116 - 24 Oct 2022

Cited by 1 | Viewed by 1659

Abstract

The orphan but highly virulent pathogen Pythium insidiosum causes pythiosis in humans and animals. Surgery is a primary treatment aiming to cure but trading off losing affected organs. Antimicrobial drugs show limited efficacy in treating pythiosis. Alternative drugs effective against the pathogen are [...] Read more.

The orphan but highly virulent pathogen Pythium insidiosum causes pythiosis in humans and animals. Surgery is a primary treatment aiming to cure but trading off losing affected organs. Antimicrobial drugs show limited efficacy in treating pythiosis. Alternative drugs effective against the pathogen are needed. In-house drug susceptibility tests (i.e., broth dilution, disc diffusion, and radial growth assays) have been established, some of which adapted the standard protocols (i.e., CLSI M38-A2 and CLSI M51) designed for fungi. Hyphal plug, hyphal suspension, and zoospore are inocula commonly used in the drug susceptibility assessment for P. insidiosum. A side-by-side comparison demonstrated that each method had advantages and limitations. Minimum inhibitory and cidal concentrations of a drug varied depending on the selected method. Material availability, user experience, and organism and drug quantities determined which susceptibility assay should be used. We employed the hyphal plug and a combination of broth dilution and radial growth methods to screen and validate the anti-P. insidiosum activities of several previously reported chemicals, including potassium iodide, triamcinolone acetonide, dimethyl sulfoxide, and ethanol, in which data on their anti-P. insidiosum efficacy are limited. We tested each chemical against 29 genetically diverse isolates of P. insidiosum. These chemicals possessed direct antimicrobial effects on the growth of the pathogen in a dose- and time-dependent manner, suggesting their potential application in pythiosis treatment. Future attempts should focus on standardizing these drug susceptibility methods, such as determining susceptibility/resistant breakpoints, so healthcare workers can confidently interpret a result and select an effective drug against P. insidiosum. Full article

(This article belongs to the Special Issue Novel, Emerging and Neglected Fungal Pathogens for Humans and Animals)

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15 pages, 794 KiB

Open AccessArticle

Efficacy of Plant-Derived Fungicides at Inhibiting Batrachochytrium salamandrivorans Growth

by Adrianna Tompros, Mark Q. Wilber, Andy Fenton, Edward Davis Carter and Matthew J. Gray

J. Fungi 2022, 8(10), 1025; https://doi.org/10.3390/jof8101025 - 28 Sep 2022

Cited by 5 | Viewed by 2548

Abstract

The emerging fungal amphibian pathogen, Batrachochytrium salamandrivorans (Bsal), is currently spreading across Europe and given its estimated invasion potential, has the capacity to decimate salamander populations worldwide. Fungicides are a promising in situ management strategy for Bsal due to their ability [...] Read more.

The emerging fungal amphibian pathogen, Batrachochytrium salamandrivorans (Bsal), is currently spreading across Europe and given its estimated invasion potential, has the capacity to decimate salamander populations worldwide. Fungicides are a promising in situ management strategy for Bsal due to their ability to treat the environment and infected individuals. However, antifungal drugs or pesticides could adversely affect the environment and non-target hosts, thus identifying safe, effective candidate fungicides for in situ treatment is needed. Here, we estimated the inhibitory fungicidal efficacy of five plant-derived fungicides (thymol, curcumin, allicin, 6-gingerol, and Pond Pimafix^®) and one chemical fungicide (Virkon^® Aquatic) against Bsal zoospores in vitro. We used a broth microdilution method in 48-well plates to test the efficacy of six concentrations per fungicide on Bsal zoospore viability. Following plate incubation, we performed cell viability assays and agar plate growth trials to estimate the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of each fungicide. All six fungicides exhibited inhibitory and fungicidal effects against Bsal growth, with estimated MIC concentrations ranging from 60 to 0.156 μg/mL for the different compounds. Allicin showed the greatest efficacy (i.e., lowest MIC and MFC) against Bsal zoospores followed by curcumin, Pond Pimafix^®, thymol, 6-gingerol, and Virkon^® Aquatic, respectively. Our results provide evidence that plant-derived fungicides are effective at inhibiting and killing Bsal zoospores in vitro and may be useful for in situ treatment. Additional studies are needed to estimate the efficacy of these fungicides at inactivating Bsal in the environment and treating Bsal-infected amphibians. Full article

(This article belongs to the Special Issue Novel, Emerging and Neglected Fungal Pathogens for Humans and Animals)

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15 pages, 15808 KiB

Open AccessArticle

Coniochaeta massiliensis sp. nov. Isolated from a Clinical Sampl28

by Jihane Kabtani, Muriel Militello and Stéphane Ranque

J. Fungi 2022, 8(10), 999; https://doi.org/10.3390/jof8100999 - 23 Sep 2022

Cited by 7 | Viewed by 1916

Abstract

The genus Coniochaeta belongs to the class Ascomycota and the family Coniochaetaceae. Some of the Coniochaeta species are plant and animal pathogens, while others are known to be primarily involved in human diseases. In the last few decades, case reports of human infections [...] Read more.

The genus Coniochaeta belongs to the class Ascomycota and the family Coniochaetaceae. Some of the Coniochaeta species are plant and animal pathogens, while others are known to be primarily involved in human diseases. In the last few decades, case reports of human infections with Coniochaeta have increased, mainly in immunocompromised hosts. We have described and characterised a new species in the genus Coniochaeta, here named Coniochaeta massiliensis (PMML0158), which was isolated from a clinical sample. Species identification and thorough description were based on apposite and reliable phylogenetic and phenotypic approaches. The phylogenetic methods included multilocus phylogenetic analyses of four genomic regions: ITS (rRNA Internal Transcribed Spacers 1 and 2), TEF-1α (Translation Elongation Factor-1alpha), B-tub2 (β-tubulin2), and D1/D2 domains (28S large subunit rRNA). The phenotypic characterisation consisted, first, of a physiological analysis using both EDX (energy-dispersive X-ray spectroscopy) and Biolog^TM advanced phenotypic technology for fixing the chemical mapping and carbon-source oxidation/assimilation profiles. Afterwards, morphological characteristics were highlighted by optical microscopy and scanning electron microscopy. The in vitro antifungal susceptibility profile was characterised using the E-test^TM exponential gradient method. The molecular analysis revealed the genetic distance between the novel species Coniochaeta massiliensis (PMML0158) and other known taxa, and the phenotypic analysis confirmed its unique chemical and physiological profile when compared with all other species of this genus. Full article

(This article belongs to the Special Issue Novel, Emerging and Neglected Fungal Pathogens for Humans and Animals)

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14 pages, 2557 KiB

Open AccessArticle

Long-Term Monitoring of the Seasonal Abundance of Basidiobolus spp. in Gecko Feces in KwaZulu-Natal (South Africa)

by Maike Claussen and Stefan Schmidt

J. Fungi 2022, 8(9), 943; https://doi.org/10.3390/jof8090943 - 07 Sep 2022

Viewed by 1278

Abstract

The fungal genus Basidiobolus is typically associated with ectothermic animals such as amphibians and reptiles. In rare cases, it can cause infections in humans, which are often misdiagnosed. Although usually restricted to tropical and subtropical countries, infections have recently been more frequently reported [...] Read more.

The fungal genus Basidiobolus is typically associated with ectothermic animals such as amphibians and reptiles. In rare cases, it can cause infections in humans, which are often misdiagnosed. Although usually restricted to tropical and subtropical countries, infections have recently been more frequently reported in hot-dry regions such as Arizona and Saudi Arabia. Reptiles such as geckos are known to shed Basidiobolus spp. via feces and frequently live in close proximity to humans. To establish the frequency and burden of Basidiobolus spp. released by geckos in a suburban location, we regularly quantified viable Basidiobolus units per gram of feces from indoors and outdoors over 3.5 years between 2018 and 2022 using a selective medium. Geckos were shedding Basidiobolus spp. in all seasons, with most counts established ranging between 5.0 and 6.5 log₁₀ cfu per gram. Statistically significant seasonal differences per location were only observed for the outside winter counts and, apparently, correlated to lower temperatures, while inside counts showed no seasonal difference. Overall, counts for droppings collected outdoors were significantly higher than counts for droppings collected indoors. Our data confirm that geckos, which frequently enter homes and are global invaders, are a regular source of this fungus. Full article

(This article belongs to the Special Issue Novel, Emerging and Neglected Fungal Pathogens for Humans and Animals)

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17 pages, 11872 KiB

Open AccessArticle

Secretome Profiling by Proteogenomic Analysis Shows Species-Specific, Temperature-Dependent, and Putative Virulence Proteins of Pythium insidiosum

by Theerapong Krajaejun, Thidarat Rujirawat, Tassanee Lohnoo, Wanta Yingyong, Pattarana Sae-Chew, Onrapak Reamtong, Weerayuth Kittichotirat and Preecha Patumcharoenpol

J. Fungi 2022, 8(5), 527; https://doi.org/10.3390/jof8050527 - 20 May 2022

Cited by 3 | Viewed by 1925

Abstract

In contrast to most pathogenic oomycetes, which infect plants, Pythium insidiosum infects both humans and animals, causing a difficult-to-treat condition called pythiosis. Most patients undergo surgical removal of an affected organ, and advanced cases could be fetal. As a successful human/animal pathogen, P. [...] Read more.

In contrast to most pathogenic oomycetes, which infect plants, Pythium insidiosum infects both humans and animals, causing a difficult-to-treat condition called pythiosis. Most patients undergo surgical removal of an affected organ, and advanced cases could be fetal. As a successful human/animal pathogen, P. insidiosum must tolerate body temperature and develop some strategies to survive and cause pathology within hosts. One of the general pathogen strategies is virulence factor secretion. Here, we used proteogenomic analysis to profile and validate the secretome of P. insidiosum, in which its genome contains 14,962 predicted proteins. Shotgun LC–MS/MS analysis of P. insidiosum proteins prepared from liquid cultures incubated at 25 and 37 °C mapped 2980 genome-predicted proteins, 9.4% of which had a predicted signal peptide. P. insidiosum might employ an alternative secretory pathway, as 90.6% of the validated secretory/extracellular proteins lacked the signal peptide. A comparison of 20 oomycete genomes showed 69 P. insidiosum–specific secretory/extracellular proteins, and these may be responsible for the host-specific infection. The differential expression analysis revealed 14 markedly upregulated proteins (particularly cyclophilin and elicitin) at body temperature which could contribute to pathogen fitness and thermotolerance. Our search through a microbial virulence database matched 518 secretory/extracellular proteins, such as urease and chaperones (including heat shock proteins), that might play roles in P. insidiosum virulence. In conclusion, the identification of the secretome promoted a better understanding of P. insidiosum biology and pathogenesis. Cyclophilin, elicitin, chaperone, and urease are top-listed secreted/extracellular proteins with putative pathogenicity properties. Such advances could lead to developing measures for the efficient detection and treatment of pythiosis. Full article

(This article belongs to the Special Issue Novel, Emerging and Neglected Fungal Pathogens for Humans and Animals)

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18 pages, 643 KiB

Open AccessArticle

Microbial Keratitis in Nepal: Predicting the Microbial Aetiology from Clinical Features

by Jeremy J. Hoffman, Reena Yadav, Sandip Das Sanyam, Pankaj Chaudhary, Abhishek Roshan, Sanjay Kumar Singh, Simon Arunga, Victor H. Hu, David Macleod, Astrid Leck and Matthew J. Burton

J. Fungi 2022, 8(2), 201; https://doi.org/10.3390/jof8020201 - 19 Feb 2022

Cited by 6 | Viewed by 2249

Abstract

Fungal corneal infection (keratitis) is a common clinical problem in South Asia. However, it is often challenging to distinguish this from other aetiologies, such as bacteria or acanthamoeba. In this prospective study, we investigated clinical and epidemiological features that can predict the microbial [...] Read more.

Fungal corneal infection (keratitis) is a common clinical problem in South Asia. However, it is often challenging to distinguish this from other aetiologies, such as bacteria or acanthamoeba. In this prospective study, we investigated clinical and epidemiological features that can predict the microbial aetiology of microbial keratitis in Nepal. We recruited patients presenting with keratitis to a tertiary eye hospital in lowland eastern Nepal between June 2019 and November 2020. A structured assessment, including demographics, history, and clinical signs, was carried out. The aetiology was investigated with in vivo confocal microscopy and corneal scrape for microscopy and culture. A predictor score was developed using odds ratios calculated to predict aetiology from features. A fungal cause was identified in 482/642 (75.1%) of cases, which increased to 532/642 (82.9%) when including mixed infections. Unusually, dematiaceous fungi accounted for half of the culture-positive cases (50.6%). Serrated infiltrate margins, patent nasolacrimal duct, raised corneal slough, and organic trauma were independently associated with fungal keratitis (p < 0.01). These four features were combined in a predictor score. The probability of fungal keratitis was 30.1% if one feature was present, increasing to 96.3% if all four were present. Whilst microbiological diagnosis is the “gold standard” to determine the aetiology of an infection, certain clinical signs can help direct the clinician to find a presumptive infectious cause, allowing appropriate treatment to be started without delay. Additionally, this study identified dematiaceous fungi, specifically Curvularia spp., as the main causative agent for fungal keratitis in this region. This novel finding warrants further research to understand potential implications and any trends over time. Full article

(This article belongs to the Special Issue Novel, Emerging and Neglected Fungal Pathogens for Humans and Animals)

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18 pages, 1201 KiB

Open AccessArticle

Global Distribution and Clinical Features of Pythiosis in Humans and Animals

by Hanna Yolanda and Theerapong Krajaejun

J. Fungi 2022, 8(2), 182; https://doi.org/10.3390/jof8020182 - 11 Feb 2022

Cited by 26 | Viewed by 3783

Abstract

Pythiosis is a difficult-to-treat infectious disease caused by Pythium insidiosum. The condition is unfamiliar among healthcare workers. Manifestation of pythiosis is similar to other fungal infections, leading to misdiagnosis and delayed treatment. The geographical extent of pythiosis at a global scale is [...] Read more.

Pythiosis is a difficult-to-treat infectious disease caused by Pythium insidiosum. The condition is unfamiliar among healthcare workers. Manifestation of pythiosis is similar to other fungal infections, leading to misdiagnosis and delayed treatment. The geographical extent of pythiosis at a global scale is unclear. This study aimed to analyze the clinical information recorded in the scientific literature to comprehensively project epidemiological characteristics, clinical features, and future trends of pythiosis. From 1980 to 2021, 4203 cases of pythiosis in humans (n = 771; 18.3%) and animals (primarily horse, dog, and cow; n = 3432; 81.7%), with an average of 103 cases/year, were recruited. Pythiosis case reports significantly increased in the last decade. Pythiosis spanned 23 tropical, subtropical, and temperate countries worldwide. Some patients acquired pythiosis from a trip to an endemic country. Strikingly, 94.3% of human cases were in India and Thailand, while 79.2% of affected animals were in the U.S.A. and Brazil. Clinical features of pythiosis varied. Vascular and ocular pythiosis were only observed in humans, whereas cutaneous/subcutaneous and gastrointestinal infections were predominant in animals. Mortality depended on host species and clinical forms: for example, none in patients with ocular pythiosis, 0.7% in cows with a cutaneous lesion, 26.8% in humans with vascular disease, 86.4% in dogs with gastrointestinal pathology, and 100% in several animals with disseminated infection. In summary, this study reports up-to-date epidemiological and clinical features of pythiosis in humans and animals. It increases awareness of this life-threatening disease, as the illness or outbreak can exist in any country, not limited to the endemic areas. Full article

(This article belongs to the Special Issue Novel, Emerging and Neglected Fungal Pathogens for Humans and Animals)

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Review

Jump to: Research, Other

16 pages, 358 KiB

Open AccessReview

Pulmonary and Extrapulmonary Manifestations of Fungal Infections Misdiagnosed as Tuberculosis: The Need for Prompt Diagnosis and Management

by Bassey E. Ekeng, Adeyinka A. Davies, Iriagbonse I. Osaigbovo, Adilia Warris, Rita O. Oladele and David W. Denning

J. Fungi 2022, 8(5), 460; https://doi.org/10.3390/jof8050460 - 28 Apr 2022

Cited by 22 | Viewed by 4463

Abstract

Fungal infections commonly present with myriad symptoms that mimic other clinical entities, notable amongst which is tuberculosis. Besides histoplasmosis and chronic pulmonary aspergillosis, which can mimic TB, this review has identified several other fungal infections which also do. A total of 80 individual [...] Read more.

Fungal infections commonly present with myriad symptoms that mimic other clinical entities, notable amongst which is tuberculosis. Besides histoplasmosis and chronic pulmonary aspergillosis, which can mimic TB, this review has identified several other fungal infections which also do. A total of 80 individual cases misdiagnosed as TB are highlighted: aspergillosis (n = 18, 22.5%), histoplasmosis (n = 16, 20%), blastomycosis (n = 14, 17.5%), cryptococcosis (n = 11, 13.8%), talaromycosis (n = 7, 8.8%), coccidioidomycosis (n = 5, 6.3%), mucormycosis (n = 4, 5%), sporotrichosis (n = 3, 3.8%), phaeohyphomycosis (n = 1, 1.3%) and chromoblastomycosis (n = 1, 1.3%). Case series from India and Pakistan reported over 100 cases of chronic and allergic bronchopulmonary aspergillosis had received anti-TB therapy before the correct diagnosis was made. Forty-five cases (56.3%) had favorable outcomes, and 25 (33.8%) died, outcome was unclear in the remainder. Seventeen (21.3%) cases were infected with human immunodeficiency virus (HIV). Diagnostic modalities were histopathology (n = 46, 57.5%), culture (n = 42, 52.5%), serology (n = 18, 22.5%), cytology (n = 2, 2.5%), gene sequencing (n = 5, 6.3%) and microscopy (n = 10, 12.5%) including Gram stain, India ink preparation, bone marrow smear and KOH mount. We conclude that the above fungal infections should always be considered or ruled out whenever a patient presents with symptoms suggestive of tuberculosis which is unconfirmed thereby reducing prolonged hospital stay and mortalities associated with a delayed or incorrect diagnosis of fungal infections. Full article

(This article belongs to the Special Issue Novel, Emerging and Neglected Fungal Pathogens for Humans and Animals)

Other

Jump to: Research, Review

6 pages, 262 KiB

Open AccessCase Report

Fatal Lodderomyces elongisporus Fungemia in a Premature, Extremely Low-Birth-Weight Neonate

by Mohammad Asadzadeh, Noura Al-Sweih, Suhail Ahmad, Seema Khan, Wadha Alfouzan and Leena Joseph

J. Fungi 2022, 8(9), 906; https://doi.org/10.3390/jof8090906 - 26 Aug 2022

Cited by 7 | Viewed by 1250

Abstract

Many rare yeasts are emerging as pathogens, causing invasive infections in susceptible hosts that are associated with poor clinical outcome. Here, we describe the first and fatal case of Lodderomyces elongisporus fungemia in a premature, extremely low-birth-weight neonate after spontaneous vaginal delivery. The [...] Read more.

Many rare yeasts are emerging as pathogens, causing invasive infections in susceptible hosts that are associated with poor clinical outcome. Here, we describe the first and fatal case of Lodderomyces elongisporus fungemia in a premature, extremely low-birth-weight neonate after spontaneous vaginal delivery. The bloodstream isolate was identified as C. parapsilosis by the VITEK 2 yeast identification system and as L. elongisporus by PCR-sequencing of the internal transcribed spacer (ITS) region of ribosomal DNA. Antifungal susceptibility testing data for the isolate, performed by the broth microdilution-based MICRONAUT-AM assay, showed susceptibility to all nine antifungal drugs tested. Despite the initiation of treatment with liposomal amphotericin B, the patient died on the same day that the blood culture yielded yeast growth. This is the first report of L. elongisporus bloodstream infection in a neonate as the previous nine cases reported in the literature occurred in adult patients. The crude mortality rate for invasive L. elongisporus infection is 50%, as only 5 of 10 patients survived. Full article

(This article belongs to the Special Issue Novel, Emerging and Neglected Fungal Pathogens for Humans and Animals)

7 pages, 795 KiB

Open AccessCase Report

Fungal Invasive Co-Infection Due to Aspergillus fumigatus and Rhizopus arrhizus: A Rhino-Orbital Presentation

by Juan Pablo Ramírez-Hinojosa, Salvador Medrano-Ahumada, Roberto Arenas, Arturo Bravo-Escobar, Sara Paraguirre-Martínez, Juan Xicohtencatl-Cortes, Erick Martínez-Herrera and Rigoberto Hernández-Castro

J. Fungi 2021, 7(12), 1096; https://doi.org/10.3390/jof7121096 - 20 Dec 2021

Cited by 4 | Viewed by 3353

Abstract

Aspergillosis and mucormycosis are filamentous fungal infections occurring predominantly in immunocompromised patients. Fulminant process with rapid infiltration of the contiguous tissue is distinctive for both type of fungi. The rhinocerebral co-infection by Aspergillus and Mucorales is very rare and is usually associated in [...] Read more.

Aspergillosis and mucormycosis are filamentous fungal infections occurring predominantly in immunocompromised patients. Fulminant process with rapid infiltration of the contiguous tissue is distinctive for both type of fungi. The rhinocerebral co-infection by Aspergillus and Mucorales is very rare and is usually associated in immunocompromised patients with a high mortality rate. This rare co-infection leads to difficulties in diagnosis, and therapeutic delays can result in a poor prognosis. Overall, the treatment of choice is surgical debridement and liposomal amphotericin B. This paper describes a combined aspergillosis and mucormycosis case in a diabetes mellitus type 2 patient with chronic ulcerations of the palatal and cheek. To our knowledge, this is the first report of an uncommon co-infection of Aspergillus fumigatus and Rhizopus arrhizus in a rhino-orbital presentation. Full article

(This article belongs to the Special Issue Novel, Emerging and Neglected Fungal Pathogens for Humans and Animals)

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