Dermatófitos: interação patógeno-hospedeiro e resistência a antifúngicos / Dermatophytes: host-pathogen interaction and antifungal resistance

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 terapêuticas. Nesta revisão, são abordados diferentes aspectos da biologia dos dermatófitos, com ênfase na interação dermatófito-hospedeiro e nos mecanismos de resistência a antifúngicos.

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.

MLL leukemia-associated rearrangements in peripheral blood lymphocytes from healthy individuals

Chromosomal translocations are characteristic of hematopoietic neoplasias and can lead to unregulated oncogene expression or the fusion of genes to yield novel functions. In recent years, different lymphoma/leukemia-associated rearrangements have been detected in healthy individuals. In this study, we used inverse PCR to screen peripheral lymphocytes from 100 healthy individuals for the presence of MLL (Mixed Lineage Leukemia) translocations. Forty-nine percent of the probands showed MLL rearrangements. Sequence analysis showed that these rearrangements were specific for MLL translocations that corresponded to t(4;11)(q21;q23) (66 percent) and t(9;11) (20 percent). However, RT-PCR failed to detect any expression of t(4;11)(q21;q23) in our population. We suggest that 11q23 rearrangements in peripheral lymphocytes from normal individuals may result from exposure to endogenous or exogenous DNA-damaging agents. In practical terms, the high susceptibility of the MLL gene to chemically-induced damage suggests that monitoring the aberrations associated with this gene in peripheral lymphocytes may be a sensitive assay for assessing genomic instability in individuals exposed to genotoxic stress.