Hidden Killers: Human Fungal Infections

Abstract

Although fungal infections contribute substantially to human morbidity and mortality, the impact of these diseases on human health is not widely appreciated. Moreover, despite the urgent need for efficient diagnostic tests and safe and effective new drugs and vaccines, research into the pathophysiology of human fungal infections lags behind that of diseases caused by other pathogens. In this Review, we highlight the importance of fungi as human pathogens and discuss the challenges we face in combating the devastating invasive infections caused by these microorganisms, in particular in immunocompromised individuals.

Eicosanoid biosynthesis influences the virulence of Candida parapsilosis

“…After C. albicans , it is the second or third leading cause of invasive candidiasis [14]. In particular, low birth weight infants are at increased risk for C. parapsilosis infection [15,16].…”

The putative flavin carrier family FlcA-C is important forAspergillus fumigatusvirulence

“…1,13 Crz1 has a C 2 H 2 zinc finger motif responsible for the binding to a CDRE (calcineurindependent response element) sequence in the promoter regions of the Crz1-regulated genes. 1,14 Fungal infections are becoming very important considering that presently there is a larger number of people dying from fungal infections than malaria and tuberculosis, what is due to the increase of the number of patients with immunosuppression. 15 The signaling by calcium is very important for fungal virulence and drug resistance.…”

“…1,14 Fungal infections are becoming very important considering that presently there is a larger number of people dying from fungal infections than malaria and tuberculosis, what is due to the increase of the number of patients with immunosuppression. 15 The signaling by calcium is very important for fungal virulence and drug resistance. 1,2 Calcineurin has been demonstrated to be required for virulence in human fungal pathogens, such as Cryptococcus spp, Candida spp, Paracoccidioides brasiliensis, and Aspergillus fumigatus; [16][17][18][19][20][21][22][23] and fungal plant pathogens, such as Sclerotinia scleotiorum, Botrytis cinerea, Magnaporthe oryza, and Ustilago spp.…”

“…1,2,[29][30][31][32][33] Aspergillus fumigatus is an opportunistic fungal pathogen and the most important species causing pulmonary fungal infections. 15,[34][35][36][37][38] Although A. fumigatus is able to cause many clinical forms, the most important is the invasive pulmonary aspergillosis (IPA), that has mortality rates as high as 80% in immunosuppressed patients. 15,[36][37][38] We have used used ChIP-seq (Chromatin Immunoprecipitation DNA sequencing) aiming to identify gene targets regulated by CrzA.…”

“…15,[34][35][36][37][38] Although A. fumigatus is able to cause many clinical forms, the most important is the invasive pulmonary aspergillosis (IPA), that has mortality rates as high as 80% in immunosuppressed patients. 15,[36][37][38] We have used used ChIP-seq (Chromatin Immunoprecipitation DNA sequencing) aiming to identify gene targets regulated by CrzA. We have identified among several genes regulated by calcium stress, flcA, encoding the putative flavin adenine dinucleotide (FAD) transmembrane transporter (the predicted homolog of the S. cerevisiae flavin carrier FLC2).…”