<i>In vitro</i> and <i>ex vivo</i> biofilms of dermatophytes: a new panorama for the study of antifungal drugs

Castelo-Branco, Débora de Souza Collares Maia; Aguiar, Lara de; Araújo, Géssica dos Santos; Lopes, Raissa Geovanna Pereira; Sales, Jamile de Alencar; Pereira-Neto, Waldemiro Aquino; Pinheiro, Adriana de Queiroz; Paixão, Germana Costa; Cordeiro, Rossana de Aguiar; Sidrim, José Júlio Costa; Brilhante, Raimunda Sâmia Nogueira; Rocha, Marcos Fábio Gadelha

doi:10.1080/08927014.2020.1811856

Cited by 21 publications

(20 citation statements)

References 26 publications

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“…The ability to form biofilm is commonly known to play a significant role in the pathogenesis of onychomycosis [5]. Moreover, it is well known that mature biofilms are associated with increased resistance to antifungal therapies [2,17,45]. Costa-Orlandi et al [46] observed that, after 72 h of incubation, dermatophyte cells were embedded within an extracellular polymeric substance, suggesting that the fungi are initiating biofilm formation.…”

Section: Discussionmentioning

confidence: 99%

Cold atmospheric pressure plasma (CAPP) as a new alternative treatment method for onychomycosis caused by Trichophyton verrucosum: in vitro studies

et al. 2021

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Purpose Anthropophilic dermatophytes as etiological factors of onychomycoses are more common than zoophilic fungi. In the case of the latter, reverse zoonoses are possible, which poses a threat to the persistence of dermatophytes in the environment. Nevertheless, without treatment, both types of tinea unguium may lead to complete nail plate destruction and secondary mixed infections with fungi and bacteria. One of the zoophilic dermatophytes that cause onychomycosis is Trichophyton verrucosum, whose prevalence has been increasing in recent years. Such infections are usually treated with allylamines and/or azoles, but such a conventional treatment of infections caused by T. verrucosum often fails or is discontinued by patients. Methods Herein, we reveal the results of our in vitro studies related to direct application of cold atmospheric pressure plasma (CAPP) on Trichophyton verrucosum growth, germination and adherence to nail as a new alternative treatment method of such types of dermatomycoses. Results Our in vitro studies showed that, while exposure to CAPP for 10 min delays germination of conidia and clearly impairs the fitness of the fungal structures, 15 min is enough to kill all fungal elements exposed to plasma. Moreover, the SEM images revealed that T. verrucosum cultures exposed to CAPP for 10 and 15 min were not able to invade the nail fragments. Conclusion The results revealed that single exposure to CAPP was able to inhibit T. verrucosum growth and infection capacity. Hence, cold atmospheric pressure plasma should be considered as a promising alternative treatment of onychomycoses.

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Section: Discussionmentioning

confidence: 99%

Cold atmospheric pressure plasma (CAPP) as a new alternative treatment method for onychomycosis caused by Trichophyton verrucosum: in vitro studies

et al. 2021

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“…Recently, it was shown that in T. mentagrophytes and M. canis , terbinafine, griseofulvin, and itraconazole, MIC values were higher for biofilms produced in vitro than for planktonic cells. In addition, biofilms produced ex vivo using cat hairs have been shown to be more tolerant to these antifungal drugs than biofilms produced in vitro [ 106 ]. This study highlights that nutritional source and availability also influence drug tolerance in biofilms and resistance in dermatophytes, as previously demonstrated [ 107 ].…”

Section: Treatment Clinical Implications and Perspectivesmentioning

confidence: 99%

State-of-the-Art Dermatophyte Infections: Epidemiology Aspects, Pathophysiology, and Resistance Mechanisms

Martinez-Rossi

Peres

Bitencourt

et al. 2021

JoF

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The burden of fungal infections is not widely appreciated. Although these infections are responsible for over one million deaths annually, it is estimated that one billion people are affected by severe fungal diseases. Mycoses of nails and skin, primarily caused by fungi known as dermatophytes, are the most common fungal infections. Trichophyton rubrum appears to be the most common causative agent of dermatophytosis, followed by Trichophyton interdigitale. An estimated 25% of the world’s population suffers from dermatomycosis. Although these infections are not lethal, they compromise the quality of life of infected patients. The outcome of antidermatophytic treatments is impaired by various conditions, such as resistance and tolerance of certain dermatophyte strains. The adage “know your enemy” must be the focus of fungal research. There is an urgent need to increase awareness about the significance of these infections with precise epidemiological data and to improve knowledge regarding fungal biology and pathogenesis, with an emphasis on adaptive mechanisms to tackle adverse conditions from host counteractions. This review outlines the current knowledge about dermatophyte infections, with a focus on signaling pathways required for fungal infection establishment and a broad perspective on cellular and molecular factors involved in antifungal resistance and tolerance.

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“…Moreover, biofilm confers more antifungal tolerance than planktonic cells [ 11 , 12 ]. Biofilms are a complex of cell populations associated with surfaces that are incorporated into the extracellular matrix.…”

Section: Introductionmentioning

confidence: 99%

Alternative Splicing in Trichophyton rubrum Occurs in Efflux Pump Transcripts in Response to Antifungal Drugs

Lopes¹,

Bitencourt²,

Sanches³

et al. 2022

JoF

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Dermatophytes are challenging to treat because they have developed many strategies to neutralize the stress triggered by antifungals. Drug tolerance is achieved by mechanisms such as drug efflux and biofilm formation, and cellular efflux is a consequence of the synergistic and compensatory regulation of efflux pumps. Alternative splicing (AS) has also been considered as a mechanism that enhances fungal adaptive responses. We used RNA-seq data from the dermatophyte Trichophyton rubrum exposed to undecanoic acid (UDA) to search for and validate AS in genes encoding efflux pumps. The magnitude of this phenomenon was evaluated using UDA and other antifungals (caspofungin, itraconazole, and terbinafine) in planktonic and biofilm cultures. In addition to the conventional isoforms, the efflux pump encoded by TERG_04309 presented two intron-retained isoforms. Biofilms trigger the simultaneous production of at least two isoforms. The intron-retained isoforms showed short lengths and topologically different organization. Furthermore, we identified the putative interaction of efflux pumps (TERG_04309 and TERG_04224). Co-expression of these genes suggests a synergistic action in antifungal resistance. Our data provide new insights into drug tolerance related to differential isoform usage and the co-expression of stress-responsive genes, which may lead to higher antifungal resistance, mainly in biofilms.

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In vitro and ex vivo biofilms of dermatophytes: a new panorama for the study of antifungal drugs

Cited by 21 publications

References 26 publications

Cold atmospheric pressure plasma (CAPP) as a new alternative treatment method for onychomycosis caused by Trichophyton verrucosum: in vitro studies

Cold atmospheric pressure plasma (CAPP) as a new alternative treatment method for onychomycosis caused by Trichophyton verrucosum: in vitro studies

State-of-the-Art Dermatophyte Infections: Epidemiology Aspects, Pathophysiology, and Resistance Mechanisms

Alternative Splicing in Trichophyton rubrum Occurs in Efflux Pump Transcripts in Response to Antifungal Drugs

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