The pH signaling transcription factor PacC mediates the growth of<i>Trichophyton rubrum</i>on human nail<i>in vitro</i>

Ferreira-Nozawa, Monica S.; Silveira, Henrique C. S.; Ono, Carlos J.; Fachin, Ana Lúcia; Rossi, Antônio; Martinez-Rossi, Nilce M.

doi:10.1080/13693780600876553

Cited by 84 publications

(92 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The single gene deletion resulted in complete loss of the gene sequence (as detected by Southern blotting and PCR) and resulted in a mutant phenotype (altered growth), strong evidence that the genome of this strain is haploid. Similarly, two recent gene deletions from T. rubrum also suggest that the strain used in that analyses is haploid (10,12). This suggests that T. rubrum is haploid but not capable of mating.…”

Section: Tools For Hypothesis Generation In the Dermatophytesmentioning

confidence: 96%

See 1 more Smart Citation

Generating and Testing Molecular Hypotheses in the Dermatophytes

et al. 2008

View full text Add to dashboard Cite

4Dermatophytes are the most common cause of fungal infections worldwide, impacting millions of individuals annually. In the United States alone, this translates into an economic impact on the health care system estimated to exceed $400 million a year for treatment alone (8,46). A recent survey conducted in 16 European countries has shown that more than one-third (35 to 40%) of the 90,000 participants were suffering with a fungal foot disease, mainly caused by dermatophytes (4). In a recent study, 22 to 50% of children in a U.S. day care center exhibited symptoms of dermatophytic scalp infections (2). Despite the prominence of dermatophyte infections and their resulting socioeconomic consequences, the research and medical communities lack a sophisticated understanding of these organisms' biology. Consequently, effective preventatives and therapeutics are lacking. These deficiencies are in large part due to the lack of genetic tools available for the study of these fungi and their host specificities. Several research efforts are now poised to produce genomic and molecular resources that will enable the molecular characterization of dermatophytes. These resources will soon be available for use by the larger research community to address many questions about the biology and pathogenesis of dermatophytes. This review will elaborate on the current status of these resources and their importance to the study of the dermatophytes. DERMATOPHYTE BIOLOGY AND DISEASEDisease. Tinea is a fungal infection of the skin, hair, or nails (reviewed in reference 34). The phrase is made specific by the addition of another term referring to a specific body location. Thus, the term "tinea pedis" refers to a fungal infection of the feet. Other tinea infections include tinea capitis (scalp or head), tinea corporis (body or trunk), and tinea unguium (nails, also known as onychomycosis). These terms do not indicate the infecting organism but the type of infection and the body location. Tinea infections are usually localized to the surface and are rarely systemic or disseminated.Fungal infections can be asymptomatic, they can be acute and severe, associated with inflammation, or they can be chronic (most common) (34). Tinea pedis usually occurs in the toe webs, with considerable scaling, fissuring, maceration, and erythema, accompanied by severe itching or burning. Tinea pedis can also localize to the sole of the foot, extending up the sides of the foot. The destruction of the skin barrier can result in bacterial superinfection. Nail infections are associated with thickening, discoloration, and pain. Scalp infections can cause irreversible hair loss.Organisms. All of the dermatophytes are ascomycetous molds, members of the class Euascomycetes that also includes Aspergillus species and the dimorphic fungi ( Fig. 1) (34). The dermatophytes are classified into three genera: Trichophyton, Microsporum, and Epidermophton. As can be seen in Fig. 2, the dermatophytes are a monophyletic clade, although the assigned genus designations within the clade ...

show abstract

Section: Tools For Hypothesis Generation In the Dermatophytesmentioning

confidence: 96%

“…Most recently, gene deletions have been obtained using protoplasting in M. canis (54) and in T rubrum (10,12). In the M. canis study, homologous recombination resulting in gene deletion was found in 2 out of 100 colonies screened-a low frequency of homologous recombination.…”

Section: Tools For Hypothesis Testing In the Dermatophytesmentioning

confidence: 99%

Generating and Testing Molecular Hypotheses in the Dermatophytes

et al. 2008

View full text Add to dashboard Cite

show abstract

“…The pacC lineage of T.rubrum, which has this inactive gene, had its infectious capacity reduced when cultured in fragments of human nail, correlating with a sharp reduction of the keratinolytic activity. 29 These works suggest that development in keratin and the consequent degration of this protein are somehow regulated by the pacC gene, interfering with the secretion of proteases with optimal activity in alkaline pH. Moreover, pH signaling and monitoring pathways could be considered dermatophyte virulence factors, allowing the development and maintenance of the infection.…”

Section: Host-dermatophyte Interaction and The Pathogenesis Of Dermatmentioning

confidence: 99%

Dermatófitos: interação patógeno-hospedeiro e resistência a antifúngicos

Peres¹,

Maranhão²,

Rossi

et al. 2010

An. Bras. Dermatol.

Self Cite

156

View full text Add to dashboard Cite

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.

show abstract

“…Genetic manipulation in dermatophyte research has been hampered by the limited number of available genetic tools and the lack of full genome sequences. Only a small number of genes have therefore been studied, and functional analysis by targeted gene disruption has been demonstrated only in a very few selected cases (6,7,35). High-throughput gene discovery by expressed sequence tag (EST) sequencing and cDNA-based microarrays provide additional valuable methodologies for the analysis of biological systems.…”

mentioning

confidence: 99%

Gene Expression Profiling in the Human Pathogenic Dermatophyte Trichophyton rubrum during Growth on Proteins

et al. 2009

View full text Add to dashboard Cite

Dermatophytes are highly specialized filamentous fungi which cause the majority of superficial mycoses in humans and animals. The high secreted proteolytic activity of these microorganisms during growth on proteins is assumed to be linked to their particular ability to exclusively infect keratinized host structures such as the skin stratum corneum, hair, and nails. Individual secreted dermatophyte proteases were recently described and linked with the in vitro digestion of keratin. However, the overall adaptation and transcriptional response of dermatophytes during protein degradation are largely unknown. To address this question, we constructed a cDNA microarray for the human pathogenic dermatophyte Trichophyton rubrum that was based on transcripts of the fungus grown on proteins. Profiles of gene expression during the growth of T. rubrum on soy and keratin protein displayed the activation of a large set of genes that encode secreted endo-and exoproteases. In addition, other specifically induced factors potentially implicated in protein utilization were identified, including heat shock proteins, transporters, metabolic enzymes, transcription factors, and hypothetical proteins with unknown functions. Of particular interest is the strong upregulation of key enzymes of the glyoxylate cycle in T. rubrum during growth on soy and keratin, namely, isocitrate lyase and malate synthase. This broad-scale transcriptional analysis of dermatophytes during growth on proteins reveals new putative pathogenicityrelated host adaptation mechanisms of these human pathogenic fungi.Dermatophytes are highly specialized fungi which are the most common agents of superficial mycoses in humans and animals (13, 34). Among the human pathogenic dermatophytes, the anthropophilic species Trichophyton rubrum is clinically the most commonly observed. In contrast to most other medically important fungi, dermatophytes are not opportunists but are obligate pathogens, infecting exclusively the skin stratum corneum, nails, or hair. The ability of dermatophytes to degrade and utilize compact hard keratin within such host structures is presumably related to their common secreted keratinolytic activity, which is therefore a major putative virulence attribute of these fungi. Individual endo-and exoproteases secreted by dermatophytes are similar to those of species of the genus Aspergillus. However, in contrast to those of Aspergillus spp., dermatophyte-secreted endoproteases are multiple and members of two large protein families, the subtilisins (Subs) S8 (serine proteases) and the fungalysins M36 (metalloproteases) (see the MEROPS peptidase database, http://merops.sanger.ac.uk) (10, 11). More than 20 genes that encode secreted proteases have been identified in dermatophytes, some of which have been characterized in detail on the molecular level (reviewed in reference 23).In order to better understand the basic mechanisms of protein degradation by dermatophytes, the secretome of different dermatophyte species was previously analyzed during in vitro growt...

show abstract

The pH signaling transcription factor PacC mediates the growth ofTrichophyton rubrumon human nailin vitro

Cited by 84 publications

References 10 publications

Generating and Testing Molecular Hypotheses in the Dermatophytes

Generating and Testing Molecular Hypotheses in the Dermatophytes

Dermatófitos: interação patógeno-hospedeiro e resistência a antifúngicos

Gene Expression Profiling in the Human Pathogenic Dermatophyte Trichophyton rubrum during Growth on Proteins

Contact Info

Product

Resources

About