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Postepy Dermatologii I Alergologii Oct 2014Chromoblastomycosis is a chronic fungal infection of the skin and subcutaneous tissue. The infection usually results from a traumatic injury and inoculation of... (Review)
Review
Chromoblastomycosis is a chronic fungal infection of the skin and subcutaneous tissue. The infection usually results from a traumatic injury and inoculation of microorganism from a specific group of dematiaceous fungi (usually Fonsecaea pedrosoi, Phialophora verrucosa, Cladophialophora carrionii). In the tissues fungi produce characteristic sclerotic cells or muriform cells. Dermal lesions can range from small nodules to large papillary-like eruptions. The disease has been described worldwide but the prevalence is higher in rural populations in countries with a tropical or subtropical climate, such as Madagascar in Africa and Brazil in South America. Diagnostic techniques are based on direct examination, culture and histopathology. Despite a variety of treatment modalities, which include long courses of antifungals, surgical excision and destructive physical therapies, the disease remains one of the most difficult deep mycotic infections to eradicate.
PubMed: 25395928
DOI: 10.5114/pdia.2014.40949 -
Journal of Clinical Microbiology Jan 2020
PubMed: 31992652
DOI: 10.1128/JCM.01657-18 -
Persoonia Jun 2017as defined by its type species is a genus of , and a member of the group known as 'black yeasts and relatives'. has been reported from mutilating human infections...
as defined by its type species is a genus of , and a member of the group known as 'black yeasts and relatives'. has been reported from mutilating human infections such as chromoblastomycosis, disseminated phaeohyphomycosis and mycetoma, while morphologically similar fungi are rather commonly isolated from the environment. Phenotypes are insufficient for correct species identification, and molecular data have revealed significant genetic variation within the complex of species currently identified as or . Multilocus analysis of 118 strains revealed the existence of five reproductively isolated species apparently having different infectious potentials. Strains of the sexual morph cluster within . The newly defined taxa differ markedly in their predilection for the human host.
PubMed: 29151624
DOI: 10.3767/003158517X692779 -
Journal of Fungi (Basel, Switzerland) Sep 2022Patients with chromoblastomycosis (CBM) suffer chronic tissue lesions that are hard to treat. Considering that biofilm is the main growth lifestyle of several pathogens...
Patients with chromoblastomycosis (CBM) suffer chronic tissue lesions that are hard to treat. Considering that biofilm is the main growth lifestyle of several pathogens and it is involved with both virulence and resistance to antimicrobial drugs, we have investigated the ability of CBM fungi to produce this complex, organized and multicellular structure. and conidial cells were able to adhere on a polystyrene abiotic substrate, differentiate into hyphae and produce a robust viable biomass containing extracellular matrix. Confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM) showed the tridimensional architecture of the mature biofilms, revealing a dense network of interconnected hyphae, inner channels and amorphous extracellular polymeric material. Interestingly, the co-culture of each fungus with THP-1 macrophage cells, used as a biotic substrate, induced the formation of a mycelial trap covering and damaging the macrophages. In addition, the biofilm-forming cells of and were more resistant to the conventional antifungal drugs than the planktonic-growing conidial cells. The efflux pump activities of and biofilms were significantly higher than those measured in conidia. Taken together, the data pointed out the biofilm formation by CBM fungi and brought up a discussion of the relevance of studies about their antifungal resistance mechanisms.
PubMed: 36135688
DOI: 10.3390/jof8090963 -
Journal of Fungi (Basel, Switzerland) Jan 2021Chromoblastomycosis is a chronic severely mutilating disease caused by fungi of the order . Classically, has been listed among these etiologic agents. This species is...
Chromoblastomycosis is a chronic severely mutilating disease caused by fungi of the order . Classically, has been listed among these etiologic agents. This species is known to occur in the environment and has been found to cause other infections like phaeohyphomycosis, while reported cases of chromoblastomycosis are scant. is phylogenetically diverse, and thus retrospective confirmation of etiology is necessary. We studied ten proven cases of chromoblastomycosis from Mexico and further analyzed the population genetics and genomics of the species to understand their pathogenicity and predilection. The clinical strains were molecularly identified as ( = 4), ( = 4), and ( = 2). No genetic distinction between clinical and environmental strains was possible. Further analysis of strains from diverse origins are needed to address eventual differences in virulence and niche predilection between the species.
PubMed: 33572699
DOI: 10.3390/jof7020095 -
Frontiers in Microbiology 2021is a dematiaceous fungus that causes mainly chromoblastomycosis, but also disseminated infections such as phaeohyphomycosis and mycetoma. These diseases are extremely...
is a dematiaceous fungus that causes mainly chromoblastomycosis, but also disseminated infections such as phaeohyphomycosis and mycetoma. These diseases are extremely hard to treat and often refractory to current antifungal therapies. In this work, we have evaluated the effect of 1,10-phenanthroline-5,6-dione (phendione) and its metal-based complexes, [Ag (phendione)]ClO and [Cu(phendione)](ClO).4HO, against , focusing on (i) conidial viability when combined with amphotericin B (AmB); (ii) biofilm formation and disarticulation events; (iii) interaction with human macrophages; and (iv) infection of larvae. The combination of AmB with each of the test compounds promoted the additive inhibition of growth, as judged by the checkerboard assay. During the biofilm formation process over polystyrene surface, sub-minimum inhibitory concentrations (MIC) of phendione and its silver(I) and copper(II) complexes were able to reduce biomass and extracellular matrix production. Moreover, a mature biofilm treated with high concentrations of the test compounds diminished biofilm viability in a concentration-dependent manner. Pre-treatment of conidial cells with the test compounds did not alter the percentage of infected THP-1 macrophages; however, [Ag(phendione)]ClO caused a significant reduction in the number of intracellular fungal cells compared to the untreated system. In addition, the killing process was significantly enhanced by post-treatment of infected macrophages with the test compounds. induced a typically cell density-dependent effect on larvae death after 7 days of infection. Interestingly, exposure to the silver(I) complex protected the larvae from infection. Collectively, the results corroborate the promising therapeutic potential of phendione-based drugs against fungal infections, including those caused by .
PubMed: 34025603
DOI: 10.3389/fmicb.2021.641258 -
Journal of Medical Case Reports Aug 2018We report a rare case of Phialophora verrucosa fungal keratitis, which required various types of treatment according to the intractable natural history of the disease.
BACKGROUND
We report a rare case of Phialophora verrucosa fungal keratitis, which required various types of treatment according to the intractable natural history of the disease.
CASE PRESENTATION
A 51-year-old Thai man with poorly controlled diabetes received a bamboo branch injury and developed a perforated corneal lesion on his left eye. A pathological study from therapeutic penetrating keratoplasty showed fungal hyphae. This was later identified as Phialophora verrucosa by polymerase chain reaction. This organism was aggressive and recalcitrant because it relapsed with two corneal grafts and was resistant to amphotericin B, natamycin, and itraconazole. However, we found that the efficacy of voriconazole was promising for treating Phialophora verrucosa. We also used corneal cross-linking to establish corneal integrity after the infection was under control.
CONCLUSIONS
Because of the chronic nature of Phialophora verrucosa, a patient's first visit may occur many years after trauma, and sometimes clinical presentation might not appear to indicate fungal infection. Therefore, a high index of suspicion is needed in this situation. Voriconazole showed good results in our case. Instead of using a more invasive keratoplasty, we used corneal cross-linking to strengthen the corneal biomechanics. To the best of our knowledge, this is the first case showing the benefit of corneal cross-linking to improve corneal biomechanics in resolved Phialophora verrucosa keratitis.
Topics: Antifungal Agents; Corneal Diseases; Corneal Injuries; Eye Infections, Fungal; Humans; Keratitis; Male; Middle Aged; Phialophora; Voriconazole
PubMed: 30121073
DOI: 10.1186/s13256-018-1765-1 -
Journal of Enzyme Inhibition and... Dec 2020causes several fungal human diseases, mainly chromoblastomycosis, which is extremely difficult to treat. Several studies have shown that human immunodeficiency virus...
causes several fungal human diseases, mainly chromoblastomycosis, which is extremely difficult to treat. Several studies have shown that human immunodeficiency virus peptidase inhibitors (HIV-PIs) are attractive candidates for antifungal therapies. This work focused on studying the action of HIV-PIs on peptidase activity secreted by and their effects on fungal proliferation and macrophage interaction. We detected a peptidase activity from able to cleave albumin, sensitive to pepstatin A and HIV-PIs, especially lopinavir, ritonavir and amprenavir, showing for the first time that this fungus secretes aspartic-type peptidase. Furthermore, lopinavir, ritonavir and nelfinavir reduced the fungal growth, causing remarkable ultrastructural alterations. Lopinavir and ritonavir also affected the conidia-macrophage adhesion and macrophage killing. Interestingly, had its growth inhibited by ritonavir combined with either itraconazole or ketoconazole. Collectively, our results support the antifungal action of HIV-PIs and their relevance as a possible alternative therapy for fungal infections.
Topics: Antifungal Agents; Aspartic Acid Proteases; Carbamates; Dose-Response Relationship, Drug; Furans; HIV Protease Inhibitors; Humans; Lopinavir; Macrophages; Microbial Sensitivity Tests; Molecular Structure; Phialophora; Ritonavir; Structure-Activity Relationship; Sulfonamides
PubMed: 32037904
DOI: 10.1080/14756366.2020.1724994 -
Mycopathologia Jun 2021Phialophora verrucosa (P. verrucosa) is a pathogen that can cause chromoblastomycosis and phaeohyphomycosis. Recent evidence suggests that neutrophils can produce...
Phialophora verrucosa (P. verrucosa) is a pathogen that can cause chromoblastomycosis and phaeohyphomycosis. Recent evidence suggests that neutrophils can produce neutrophil extracellular traps (NETs) that can protect against invasive pathogens. As such, we herein explored the in vitro functional importance of P. verrucosa-induced NET formation. By assessing the co-localization of neutrophil elastase and DNA, we were able to confirm the formation of classical NETs entrapping P. verrucosa specimens. Sytox Green was then used to stain these NETs following neutrophil infection with P. verrucosa in order to quantify the formation of these extracellular structures. NET formation was induced upon neutrophil exposure to both live, UV-inactivated, and dead P. verrucosa fungi. The ability of these NETs to kill fungal hyphae and conidia was demonstrated through MTT and pouring plate assays, respectively. Overall, our results confirmed that P. verrucosa was able to trigger the production of NETs, suggesting that these extracellular structures may represent an important innate immune effector mechanism controlling physiological responses to P. verrucosa infection, thereby aiding in pathogen control during the acute phases of infection.
Topics: Extracellular Traps; Humans; Hyphae; Neutrophils; Phialophora
PubMed: 34013384
DOI: 10.1007/s11046-021-00554-0 -
Frontiers in Microbiology 2017is a dematiaceous fungus able to cause chromoblastomycosis, phaeohyphomycosis and mycetoma. All these fungal diseases are extremely difficult to treat and often...
is a dematiaceous fungus able to cause chromoblastomycosis, phaeohyphomycosis and mycetoma. All these fungal diseases are extremely difficult to treat and often refractory to the current therapeutic approaches. Therefore, there is an urgent necessity to develop new antifungal agents to combat these mycoses. In this context, the aim of the present work was to investigate the effect of 1,10-phenanthroline-5,6-dione (phendione) and its metal-based derivatives [Ag(phendione)]ClO = ([Ag(phendione)]) and [Cu(phendione)](ClO).4HO = ([Cu(phendione)]) on crucial physiological events of conidial cells. Using the CLSI protocol, we have shown that phendione, [Ag(phendione)] and [Cu(phendione)] were able to inhibit fungal proliferation, presenting MIC/IC values of 12.0/7.0, 4.0/2.4, and 5.0/1.8 μM, respectively. [Cu(phendione)] had fungicidal action and when combined with amphotericin B, both at sub-MIC (½ × MIC) concentrations, significantly reduced (~40%) the fungal growth. Cell morphology changes inflicted by phendione and its metal-based derivatives was corroborated by scanning electron microscopy, which revealed irreversible ultrastructural changes like surface invaginations, cell disruption and shrinkages. Furthermore, [Cu(phendione)] and [Ag(phendione)] were able to inhibit metallopeptidase activity secreted by conidia by approximately 85 and 40%, respectively. Ergosterol content was reduced (~50%) after the treatment of conidial cells with both phendione and [Ag(phendione)]. To different degrees, all of the test compounds were able to disturb the conidia-into-mycelia transformation. Phendione and its Ag and Cu complexes may represent a promising new group of antimicrobial agents effective at inhibiting growth and morphogenesis.
PubMed: 28194139
DOI: 10.3389/fmicb.2017.00076