Molecular cloning and characterization of a novel ABC transporter gene in the human pathogen<i>Trichophyton rubrum</i>

Cervelatti, Eliane Patrícia; Fachin, AL; Ferreira-Nozawa,; Martinez-Rossi, Nilce M.

doi:10.1080/13693780500220449

Cited by 46 publications

(42 citation statements)

References 37 publications

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“…Under the selective pressure of terbinafi ne exposure, an increase in the expression of energy-dependent effl ux transporters can be observed in yeast; 27 however, the expression level of orthologous transporters remains unchanged in dermatophytes. 28 Similarly, fi lamentous fungi can upregulate the expression of an enzyme that catalyzes the breakdown of terbinafi ne 29 but this has not been reported for dermatophytes.…”

Section: Clinical Mycologymentioning

confidence: 99%

Update on terbinafine with a focus on dermatophytoses

Newland¹,

Abdel‐Rahman

2009

CCID

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Since terbinafi ne was introduced on the world market 17 years ago, it has become the leading antifungal for the treatment of superfi cial fungal infections, aided by unique pharmacologic and microbiologic profi les. This article reviews mode of action, antimycotic spectrum and disposition profi le of terbinafi ne. It examines the data, accumulated over 15 years, on the comparative effi cacy of terbinafi ne (vs griseofulvin, itraconazole, fl uconazole) in the management of the infections for which it is primarily indicated (eg, dermatophytoses) and provides a brief discussion on its use for the treatment of non-dermatophyte infections. Finally, the available data on the newest topical and systemic formulations are introduced.

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Section: Clinical Mycologymentioning

confidence: 99%

Update on terbinafine with a focus on dermatophytoses

Newland¹,

Abdel‐Rahman

2009

CCID

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“…37 In T. rubrum, two ATP binding cassette transporters, TruMDR1 e TruMDR2, were identified showing importance not only in the process of resistance to various antifungal drugs, but also in enzyme secretion and probably in the pathogenicity of this dermatophyte. [40][41][42] It has also been described that a mutation in the gene that codifies the enzyme squalene epoxidase (ErgA), target of terbinafine, made the fungi A. nidulans, Aspergillus fumigatus and T. rubrum highly resistant to this drug. 37,43 Fungi respond to stimuli from the environment by the activation of several signal transduction pathways responsible for monitoring environmental alterations to allow the functioning of physiological mechanisms that adapt them to stress conditions, developing defense or cell tolerance responses.…”

Section: Treatment Of Dermatophytoses and The Issue Of Antifungal Resmentioning

confidence: 99%

Dermatófitos: interação patógeno-hospedeiro e resistência a antifúngicos

Peres¹,

Maranhão²,

Rossi

et al. 2010

An. Bras. Dermatol.

156

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Cutaneous mycoses are among the most common infections in humans and have become an important public health issue because they cause invasive infections in immunocompromised patients. During the infectious process, dermatophyte-host interactions trigger specific metabolic adaptations that allow the pathogen to adhere to and penetrate the host tissue, scavenge nutrients, and overcome the host defense mechanisms. This metabolic shift and the interplay between metabolism, morphogenesis and stress response are important factors that have been extensively studied in several pathogens. Host cells also respond to the pathogen stimuli by activating intracellular signaling pathways that trigger the immune response against the infectious agent. The comprehension of the molecular aspects of these responses may help to establish new therapeutical strategies. In this review, different aspects of the biology of dermatophytes are addressed, with emphasis on the dermatophyte-host interaction and the mechanisms of antifungal resistance. Keywords: Antifungal agents; Dermatomycoses; Drug resistance, fungal; Host-pathogen interactions Resumo: As micoses cutâneas estão entre as infecções mais comuns em humanos e se tornaram um importante problema de saúde pública, principalmente por causarem infecções invasivas em pacientes imunodeprimidos. Durante a infecção, a interação dermatófito-hospedeiro desencadeia adaptações metabólicas específicas que permitem aos patógenos aderirem e penetrarem no tecido, remodelando seu metabolismo para captar nutrientes e superar os mecanismos de defesa do hospedeiro. Esse remodelamento metabólico e a inter-relação entre metabolismo, morfogênese e resposta ao estresse são importantes fatores que estão sendo intensamente avaliados em diversos patógenos. As células do hospedeiro também respondem aos estímulos do patógeno, ativando vias de sinalização intracelular que culminam no desencadeamento de uma resposta imune contra o agente infeccioso. O entendimento molecular dessas respostas metabólicas pode ajudar no estabelecimento de novas estratégias terapêuti-cas. Nesta revisão, são abordados diferentes aspectos da biologia dos dermatófitos, com ênfase na interação dermatófito-hospedeiro e nos mecanismos de resistência a antifúngicos.

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“…It is interesting to note the significantly increasing occurrence of the 1-I genotype (from 35 to 55%) when testing isolates obtained post-treatment, and that for two isolates, an increase in MIC values was observed, mainly for azole derivates. Cervelatti et al [24] evidenced the presence of mRNA corresponding to the efflux pump gene in T. rubrum after in vitro exposure to subinhibitory concentrations of antifungal agents, especially of ketoconazole, itraconazole and griseofulvin. The data obtained in our study attempt to consider the relevance of in vivo drug resistance for dermatophytosis caused by T. rubrum, especially for onychomycosis.…”

Section: Discussionmentioning

confidence: 98%