scholarly journals A new humanized antibody is effective against pathogenic fungi in vitro

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tomas Di Mambro ◽  
Tania Vanzolini ◽  
Pierpaolo Bruscolini ◽  
Sergio Perez-Gaviro ◽  
Emanuele Marra ◽  
...  
Keyword(s):  
Fungal Infections ◽  
Pathogenic Fungi ◽  
Invasive Fungal Infections ◽  
Enhancement Effect ◽  
Neoplastic Disease ◽  
Transplantation Surgery ◽  
Humanized Monoclonal Antibody ◽  
Invasive Diseases ◽  
Vital Component

AbstractInvasive fungal infections mainly affect patients undergoing transplantation, surgery, neoplastic disease, immunocompromised subjects and premature infants, and cause over 1.5 million deaths every year. The most common fungi isolated in invasive diseases are Candida spp., Cryptococcus spp., and Aspergillus spp. and even if four classes of antifungals are available (Azoles, Echinocandins, Polyenes and Pyrimidine analogues), the side effects of drugs and fungal acquired and innate resistance represent the major hurdles to be overcome. Monoclonal antibodies are powerful tools currently used as diagnostic and therapeutic agents in different clinical contexts but not yet developed for the treatment of invasive fungal infections. In this paper we report the development of the first humanized monoclonal antibody specific for β-1,3 glucans, a vital component of several pathogenic fungi. H5K1 has been tested on C. auris, one of the most urgent threats and resulted efficient both alone and in combination with Caspofungin and Amphotericin B showing an enhancement effect. Our results support further preclinical and clinical developments for the use of H5K1 in the treatment of patients in need.

Identification and in Vitro Susceptibility Pattern of Fungal Pathogens in Immunocompromised Patients with invasive Fungal Infections

2021 ◽  
Vol 30 (3) ◽  
pp. 127-134
Author(s):  
Shaimaa A.S. Selem ◽  
Neveen A. Hassan ◽  
Mohamed Z. Abd El-Rahman ◽  
Doaa M. Abd El-Kareem
Keyword(s):  
Intensive Care ◽  
Fungal Infection ◽  
Fungal Pathogens ◽  
Fungal Infections ◽  
Antifungal Susceptibility ◽  
Invasive Fungal Infections ◽  
Immunocompromised Patients ◽  
University Hospitals ◽  
Vitek 2

Background: In intensive care units, invasive fungal infections have become more common, particularly among immunocompromised patients. Early identification and starting the treatment of those patients with antifungal therapy is critical for preventing unnecessary use of toxic antifungal agents. Objective: The aim of this research is to determine which common fungi cause invasive fungal infection in immunocompromised patients, as well as their antifungal susceptibility patterns in vitro, in Assiut University Hospitals. Methodology: This was a hospital based descriptive study conducted on 120 patients with clinical suspicion of having fungal infections admitted at different Intensive Care Units (ICUs) at Assiut University Hospitals. Direct microscopic examination and inoculation on Sabouraud Dextrose Agar (SDA) were performed on the collected specimens. Isolated yeasts were classified using phenotypic methods such as chromogenic media (Brilliance Candida agar), germ tube examination, and the Vitek 2 system for certain isolates, while the identification of mould isolates was primarily based on macroscopic and microscopic characteristics. Moulds were tested in vitro for antifungal susceptibility using the disc diffusion, and yeast were tested using Vitek 2 device cards. Results: In this study, 100 out of 120 (83.3%) of the samples were positive for fungal infection. Candida and Aspergillus species were the most commonly isolated fungal pathogens. The isolates had the highest sensitivity to Amphotericin B (95 %), followed by Micafungin (94 %) in an in vitro sensitivity survey. Conclusion: Invasive fungal infections are a leading cause of morbidity and mortality in immunocompromised patients, with Candida albicans being the most frequently isolated yeast from various clinical specimens; however, the rise in resistance, especially to azoles, is a major concern.

scholarly journals 2106. Evaluation of Isavuconazole for the Prophylaxis and Treatment of Invasive Fungal Infections at a Large Academic Medical Center

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S712-S713
Author(s):  
Christine Vu ◽  
Meenakshi Rana ◽  
Patricia Saunders-Hao
Keyword(s):  
Fungal Infections ◽  
Medical Center ◽  
Academic Medical Center ◽  
Retrospective Chart Review ◽  
Invasive Fungal Infections ◽  
Prescribing Practices ◽  
Candida Spp ◽  
Antifungal Stewardship ◽  
Hospital Formulary

Abstract Background Isavuconazole is an azole antifungal with in vitro activity against various fungi, including Candida spp, Aspergillus, and Mucormycetes. Currently, isavuconazole is FDA approved for the treatment of invasive aspergillosis and mucormycosis; however, there remains limited data to support prophylaxis use. Compared with other first-line azoles, isavuconazole’s broad spectrum of activity, favorable safety profile, and oral bioavailability makes it an attractive antifungal option. In July 2017, isavuconazole was added to our hospital formulary as a restricted antimicrobial. Since then, we have seen increased use for both prophylaxis and treatment of invasive fungal infections. Methods A single-center, retrospective chart review was conducted on adult patients who received at least 1 dose of isavuconazole at The Mount Sinai Hospital between July 1, 2017 and December 31, 2018. The electronic medical record was utilized to collect information on therapeutic indication, dosing, formulation, duration, reasons for switching to isavuconazole, prior antifungals, and proven or probable breakthrough invasive fungal infections (bIFIs) based on EORTG/MTG definitions. Results 54 patients received 61 courses of isavuconazole. Reasons for switching to isavuconazole are described in Table 1. Eleven patients received inappropriate intravenous formulations and 14% of orders were prescribed isavuconazole without a loading dose (Table 2). We identified 4 proven/probable bIFIs, representing 7.4% of patients and 6.6% of courses (Table 3). All patients died within 60 days of bIFI onset. Conclusion Since its addition to hospital formulary, we have observed varying isavuconazole prescribing practices, highlighting the need for improved antifungal stewardship. Rates of bIFIs on isavuconazole were lower than previously reported studies. Additional studies are needed to provide guidance on isavuconazole use and determine its role as prophylaxis therapy. Disclosures All authors: No reported disclosures.

scholarly journals Identification of a New Class of Antifungals Targeting the Synthesis of Fungal Sphingolipids

mBio ◽  
2015 ◽  
Vol 6 (3) ◽  
Author(s):  
Visesato Mor ◽  
Antonella Rella ◽  
Amir M. Farnoud ◽  
Ashutosh Singh ◽  
Mansa Munshi ◽  
...  
Keyword(s):  
Cell Cycle Progression ◽  
Fungal Infections ◽  
Pathogenic Fungi ◽  
Antifungal Drugs ◽  
Sequencing Analysis ◽  
Fungal Cell ◽  
New Class ◽  
Narrow Spectrum

ABSTRACT Recent estimates suggest that >300 million people are afflicted by serious fungal infections worldwide. Current antifungal drugs are static and toxic and/or have a narrow spectrum of activity. Thus, there is an urgent need for the development of new antifungal drugs. The fungal sphingolipid glucosylceramide (GlcCer) is critical in promoting virulence of a variety of human-pathogenic fungi. In this study, we screened a synthetic drug library for compounds that target the synthesis of fungal, but not mammalian, GlcCer and found two compounds [N′-(3-bromo-4-hydroxybenzylidene)-2-methylbenzohydrazide (BHBM) and its derivative, 3-bromo-N′-(3-bromo-4-hydroxybenzylidene) benzohydrazide (D0)] that were highly effective in vitro and in vivo against several pathogenic fungi. BHBM and D0 were well tolerated in animals and are highly synergistic or additive to current antifungals. BHBM and D0 significantly affected fungal cell morphology and resulted in the accumulation of intracellular vesicles. Deep-sequencing analysis of drug-resistant mutants revealed that four protein products, encoded by genes APL5, COS111, MKK1, and STE2, which are involved in vesicular transport and cell cycle progression, are targeted by BHBM. IMPORTANCE Fungal infections are a significant cause of morbidity and mortality worldwide. Current antifungal drugs suffer from various drawbacks, including toxicity, drug resistance, and narrow spectrum of activity. In this study, we have demonstrated that pharmaceutical inhibition of fungal glucosylceramide presents a new opportunity to treat cryptococcosis and various other fungal infections. In addition to being effective against pathogenic fungi, the compounds discovered in this study were well tolerated by animals and additive to current antifungals. These findings suggest that these drugs might pave the way for the development of a new class of antifungals.

scholarly journals Combination Treatment of Invasive Fungal Infections

2005 ◽  
Vol 18 (1) ◽  
pp. 163-194 ◽  
Author(s):  
Pranab K. Mukherjee ◽  
Daniel J. Sheehan ◽  
Christopher A. Hitchcock ◽  
Mahmoud A. Ghannoum
Keyword(s):  
Treatment Outcome ◽  
Combination Therapy ◽  
Fungal Infections ◽  
Clinical Success ◽  
Treatment Strategies ◽  
Historical Review ◽  
Invasive Fungal Infections ◽  
High Morbidity ◽  
Interpretation Criteria

SUMMARY The persistence of high morbidity and mortality from systemic fungal infections despite the availability of novel antifungals points to the need for effective treatment strategies. Treatment of invasive fungal infections is often hampered by drug toxicity, tolerability, and specificity issues, and added complications often arise due to the lack of diagnostic tests and to treatment complexities. Combination therapy has been suggested as a possible approach to improve treatment outcome. In this article, we undertake a historical review of studies of combination therapy and also focus on recent studies involving newly approved antifungal agents. The limitations surrounding antifungal combinations include nonuniform interpretation criteria, inability to predict the likelihood of clinical success, strain variability, and variations in pharmacodynamic/pharmacokinetic properties of antifungals used in combination. The issue of antagonism between polyenes and azoles is beginning to be addressed, but data regarding other drug combinations are not adequate for us to draw definite conclusions. However, recent data have identified potentially useful combinations. Standardization of assay methods and adoption of common interpretive criteria are essential to avoid discrepancies between different in vitro studies. Larger clinical trials are needed to assess whether combination therapy improves survival and treatment outcome in the most seriously debilitated patients afflicted with life-threatening fungal infections.

Caspofungin Acetate for Treatment of Invasive Fungal Infections

2003 ◽  
Vol 37 (1) ◽  
pp. 90-98 ◽  
Author(s):  
Staci A Pacetti ◽  
Steven P Gelone
Keyword(s):  
Clinical Trials ◽  
Invasive Aspergillosis ◽  
Clinical Data ◽  
Treatment Guidelines ◽  
Fungal Infections ◽  
Invasive Fungal Infections ◽  
Current Therapy ◽  
Candida Spp ◽  
Fungal Cell

OBJECTIVE To briefly discuss the changing epidemiology of fungal infections and review currently available agents; provide a review of caspofungin; and discuss its pharmacology, pharmacokinetics, dosing guidelines, safety and efficacy, and role in the treatment of invasive fungal infections as it relates to current antifungal therapy. DATA SOURCES A MEDLINE (1966 to August 2002) database search using key words caspofungin, echino candins, fungal infections, and invasive aspergillosis, was completed to identify relevant articles including reviews, recent studies, treatment guidelines, and data from Merck and Company. STUDY SELECTION In vitro studies and all clinical trials were evaluated to summarize the clinical efficacy and safety of caspofungin. DATA SYNTHESIS The incidence of fungal infections is increasing as the population at risk expands. Cost, resistance, and morbidity and mortality are key issues. Adding to the antifungal armamentarium is necessary to address these therapeutic dilemmas. Caspofungin is the first member of a new class of antifungal agents, the echinocandins, to be approved for clinical use. Caspofungin is classified as a glucan synthase inhibitor and represents a class of agents with a novel mechanism of action. Unlike currently available agents (polyenes, pyrimidines, azoles) that exert their effect on the fungal cell membrane, the echinocandins are the first agents to inhibit fungal cell wall synthesis. Caspofungin exhibits activity against Aspergillus spp. and Candida spp., including non-albicans species. Data from clinical trials demonstrate that caspofungin is effective in patients with invasive aspergillosis as well as candida esophagitis. Its Food and Drug Administration–approved indication is limited to invasive aspergillosis refractory to or intolerant of current therapy. CONCLUSIONS Caspofungin has activity against Aspergillus spp. as well as a variety of Candida spp. Clinical data support its usefulness in the treatment of invasive aspergillosis and select candida infections. As additional clinical data become available, it seems likely that the therapeutic role of caspofungin will expand. THIS ARTICLE IS APPROVED FOR CONTINUING EDUCATION CREDIT ACPE UNIVERSAL PROGRAM NUMBER: 407-000-03-001-H01

Posaconazole: An Oral Triazole with an Extended Spectrum of Activity

2008 ◽  
Vol 42 (10) ◽  
pp. 1429-1438 ◽  
Author(s):  
Erik J Rachwalski ◽  
Jeffrey T Wieczorkiewicz ◽  
Marc H Scheetz
Keyword(s):  
English Language ◽  
Fungal Infections ◽  
Data Extraction ◽  
Treatment Options ◽  
Drug Application ◽  
Invasive Fungal Infections ◽  
Therapeutic Drug ◽  
Hematopoietic Stem ◽  
Yeasts And Molds

Objective: To summarize the published clinical data on posaconazole, critically review the New Drug Application data submitted to the Food and Drug Administration, and provide information critical for evaluation and formulary positioning. Data Sources: Reported investigations were identified from MEDLINE (1966-June 30, 2008), bibliographies of manuscripts, www.clinicaltrials.gov , and www.fda.gov . Study Selection and Data Extraction: English-language articles were selected. AN available in vitro, animal, clinical, and human studies describing the pharmacology, pharmacokinetics, pharmacodynamics, efficacy, safety, and adverse events of posaconazole were reviewed. Data Synthesis: Posaconazole is an oral broad-spectrum triazole with activity against many yeasts and molds. Resistance to posaconazole has been reported, but has been rare to date. Posaconazole, in doses of 200 mg 3 limes daily, reduced breakthrough invasive fungal infections (OR 0.30; 95% CI 0.12 to 0.71) and aspergillosis incidence (OR 0.31; 95% CI 0.13 to 0.75) in patients receiving hematopoietic stem-cell transplants compared with those receiving fluconazole. Similarly, the same regimen of posaconazole reduced invasive fungal infections (95% CI -9.7 to -2.5) and aspergillosis (CI not reported, p < 0.001) when compared with fluconazole and itraconazole in neutropenic patients. Posaconazole is non-inferior to fluconazole for treatment of oropharyngeal candidiasis (95% CI -6.6 to 5.0), but necessity for this indication remains unclear, as many other treatment options exist. Smaller investigations have analyzed use of posaconazole for patients requiring salvage or alternative treatment for zygomycosis, fusarbsis, cryptococcal meningitis, coccidioidomycosis, and histoplasmosis. Studies are needed to clarify efficacy for such expanded use, and therapeutic drug monitoring may improve outcomes. The most common adverse effects associated with the use of posaconazole include headache, fever, nausea, vomiting, and diarrhea. Conclusions: Posaconazole appears to be a valuable and promising addition to the antifungal armamentarium for prophylaxis and treatment of various fungal processes. At this time, posaconazole should probably be reserved for prophylaxis in patients at high risk for invasive fungal infection, as salvage therapy in refractory or resistant infections, or for patients with intolerance to other therapies.

scholarly journals DC-SIGN targets amphotericin B-loaded liposomes to diverse pathogenic fungi

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Suresh Ambati ◽  
Tuyetnhu Pham ◽  
Zachary A. Lewis ◽  
Xiaorong Lin ◽  
Richard B. Meagher
Keyword(s):  
Amphotericin B ◽  
Fungal Infections ◽  
Pathogenic Fungi ◽  
Antifungal Drugs ◽  
Protein Isoforms ◽  
Viral Pathogens ◽  
Life Threatening ◽  
Better Than

Abstract Background Life-threatening invasive fungal infections are treated with antifungal drugs such as Amphotericin B (AmB) loaded liposomes. Our goal herein was to show that targeting liposomal AmB to fungal cells with the C-type lectin pathogen recognition receptor DC-SIGN improves antifungal activity. DC-SIGN binds variously crosslinked mannose-rich and fucosylated glycans and lipomannans that are expressed by helminth, protist, fungal, bacterial and viral pathogens including three of the most life-threatening fungi, Aspergillus fumigatus, Candida albicans and Cryptococcus neoformans. Ligand recognition by human DC-SIGN is provided by a carbohydrate recognition domain (CRD) linked to the membrane transit and signaling sequences. Different combinations of the eight neck repeats (NR1 to NR8) expressed in different protein isoforms may alter the orientation of the CRD to enhance its binding to different glycans. Results We prepared two recombinant isoforms combining the CRD with NR1 and NR2 in isoform DCS12 and with NR7 and NR8 in isoform DCS78 and coupled them to a lipid carrier. These constructs were inserted into the membrane of pegylated AmB loaded liposomes AmB-LLs to produce DCS12-AmB-LLs and DCS78-AmB-LLs. Relative to AmB-LLs and Bovine Serum Albumin coated BSA-AmB-LLs, DCS12-AmB-LLs and DCS78-AmB-LLs bound more efficiently to the exopolysaccharide matrices produced by A. fumigatus, C. albicans and C. neoformans in vitro, with DCS12-AmB-LLs performing better than DCS78-AmB-LLs. DCS12-AmB-LLs inhibited and/or killed all three species in vitro significantly better than AmB-LLs or BSA-AmB-LLs. In mouse models of invasive candidiasis and pulmonary aspergillosis, one low dose of DCS12-AmB-LLs significantly reduced the fungal burden in the kidneys and lungs, respectively, several-fold relative to AmB-LLs. Conclusions DC-SIGN’s CRD specifically targeted antifungal liposomes to three highly evolutionarily diverse pathogenic fungi and enhanced the antifungal efficacy of liposomal AmB both in vitro and in vivo. Targeting significantly reduced the effective dose of antifungal drug, which may reduce drug toxicity, be effective in overcoming dose dependent drug resistance, and more effectively kill persister cells. In addition to fungi, DC-SIGN targeting of liposomal packaged anti-infectives have the potential to alter treatment paradigms for a wide variety of pathogens from different kingdoms including protozoans, helminths, bacteria, and viruses which express its cognate ligands.

Invasive Fungal Infections in the Critically Ill Patient

2005 ◽  
Vol 18 (1) ◽  
pp. 9-17 ◽  
Author(s):  
Craig A. Martin
Keyword(s):  
Critically Ill ◽  
Antifungal Agents ◽  
Clinical Decision Making ◽  
Fungal Infections ◽  
Significant Risk ◽  
Pathogenic Fungi ◽  
Clinical Decision ◽  
Invasive Fungal Infections ◽  
Critically Ill Patient ◽  
Advantages And Disadvantages

Invasive fungal infections have become an increasingly prevalent and disturbing problem in critically ill patients. The advent of broad-spectrum antibacterial therapy and immunosuppressant therapy, among other factors such as mechanical ventilation, places the intensive care patient at significant risk for infection with pathogenic fungi. Most patients who become infected with invasive fungi, especially Candida species, have been previously colonized with the offending organism, lending to the notion that colonization precedes infection inmany cases. Despite an ever-increasing array of antifungal therapy for these infections, mortality rates remain extremely high, especially when the bloodstream is the primary site of infection. In addition, a shift toward more resistant pathogens such asCandida glabrata, Candida krusei, and moldswill provide clinicianswith therapeutic challenges for many years. The wide variation in acquisition cost across antifungal agents adds an additional layer of complexity to clinical decision making. Newer antifungal agents, each with its own advantages and disadvantages, have become available in recent years. Placing each agent in its appropriate niche is a dilemma that has yet to be solved.

scholarly journals Comparative Genomics of Pneumocystis Species Suggests the Absence of Genes for myo-Inositol Synthesis and Reliance on Inositol Transport and Metabolism

mBio ◽  
2014 ◽  
Vol 5 (6) ◽  
Author(s):  
Aleksey Porollo ◽  
Thomas M. Sesterhenn ◽  
Margaret S. Collins ◽  
Jeffrey A. Welge ◽  
Melanie T. Cushion
Keyword(s):  
Fission Yeast ◽  
Fungal Infections ◽  
Inositol Phosphate ◽  
Pathogenic Fungi ◽  
Phosphate Metabolism ◽  
Transport Pathways ◽  
Content Type ◽  
Inositol Phosphate Metabolism ◽  
Genes Encoding

ABSTRACTIn the context of deciphering the metabolic strategies of the obligate pathogenic fungi in the genusPneumocystis, the genomes of three species (P. carinii,P. murina, andP. jirovecii) were compared among themselves and with the free-living, phylogenetically related fission yeast (Schizosaccharomyces pombe). The underrepresentation of amino acid metabolism pathways compared to those inS. pombe, as well as the incomplete steroid biosynthesis pathway, were confirmed forP. cariniiandP. jiroveciiand extended toP. murina. All threePneumocystisspecies showed overrepresentation of the inositol phosphate metabolism pathway compared to that in the fission yeast. In addition to those known inS. pombe, four genes, encoding inositol-polyphosphate multikinase (EC 2.7.1.151), inositol-pentakisphosphate 2-kinase (EC 2.7.1.158), phosphoinositide 5-phosphatase (EC 3.1.3.36), and inositol-1,4-bisphosphate 1-phosphatase (EC 3.1.3.57), were identified in the two rodentPneumocystisgenomes,P. cariniiandP. murina. TheP. jiroveciigenome appeared to contain three of these genes but lacked phosphoinositide 5-phosphatase. Notably, two genes encoding enzymes essential formyo-inositol synthesis, inositol-1-phosphate synthase (INO1) and inositol monophosphatase (INM1), were absent from all three genomes, suggesting thatPneumocystisspecies are inositol auxotrophs. In keeping with the need to acquire exogenous inositol, two genes with products homologous to fungal inositol transporters, ITR1 and ITR2, were identified inP. cariniiandP. murina, whileP. jiroveciicontained only the ITR1 homolog. The ITR and inositol metabolism genes inP. murinaandP. cariniiwere expressed during fulminant infection as determined by reverse transcriptase real-time PCR of cDNA from infected lung tissue. Supplementation ofin vitroculture with inositol yielded significant improvement of the viability ofP. cariniifor days 7 through 14.IMPORTANCEMicrobes in the genusPneumocystisare obligate pathogenic fungi that reside in mammalian lungs and causePneumocystispneumonia in hosts with weakened immune systems. These fungal infections are not responsive to standard antifungal therapy. A long-termin vitroculture system is not available for these fungi, impeding the study of their biology and genetics and new drug development. Given that all genomes of thePneumocystisspecies analyzed lack the genes for inositol synthesis and contain inositol transporters,Pneumocystisfungi, likeS. pombe, appear to be inositol auxotrophs. Inositol is important for the pathogenesis, virulence, and mating processes inCandida albicansandCryptococcus neoformans, suggesting similar importance within thePneumocystisspecies as well. This is the first report to (i) characterize genes in the inositol phosphate metabolism and transport pathways inPneumocystisspecies and (ii) identify inositol as a supplement that improved the viability ofP. cariniiinin vitroculture.

Evaluation of the in vitro and in vivo dimorphism ofSporothrix schenckii,Blastomyces dermatitidis, andParacoccidioides brasiliensisisolates after preservation in mineral oil

2004 ◽  
Vol 50 (6) ◽  
pp. 445-449 ◽  
Author(s):  
Renata Ferretti de Lima ◽  
Marcelly Maria dos Santos Brito ◽  
Guido Manoel Vidal Schäffer ◽  
Osana Cunha de Lima ◽  
Cintia de Moraes Borba
Keyword(s):  
Fungal Infections ◽  
Paracoccidioides Brasiliensis ◽  
Sporothrix Schenckii ◽  
Brain Heart Infusion ◽  
Morphological Differentiation ◽  
Pathogenic Fungi ◽  
Mineral Oil ◽  
Blastomyces Dermatitidis

Morphological differentiation has commanded attention for its putative impact on the pathogenesis of invasive fungal infections. We evaluated in vitro and in vivo the dimorphism from mycelial to yeast-phase of Sporothrix schenckii, Blastomyces dermatitidis and Paracoccidioides brasiliensis isolates, two strains for each species, preserved in mineral oil. S. schenckii strains showed typical micromorphology at 25 °C but one strain was unable to complete the dimorphic process in vitro. After in vivo passage through mice the strains had the ability to turn into yeast-like cells and to form colonies on brain-heart infusion medium at 36 °C. B. dermatitidis strains grew as dirty white to brownish membranous colonies at 25 °C and their micromorphology showed thin filaments with single hyaline conidia. At 36 °C the colonies did not differ from those grown at 25 °C, but produced a transitional micromorphology. P. brasiliensis strains grew as cream-colored cerebriform colonies at 25 °C showing a transitional morphology. B. dermatitidis and P. brasiliensis strains did not turn into yeast-like cells in vivo. The present results demonstrate that B. dermatitidis and P. brasiliensis strains were unable to complete the dimorphic process even after in vivo passage, in contrast to the S. schenckii strain.Key words: pathogenic fungi, in vitro storage, in vivo passage, morphogenesis.

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