Candida duobushaemulonii: an emerging rare pathogenic yeast isolated from recurrent vulvovaginal candidiasis in Brazil

The aim of this study was to identify Candida species isolated from women diagnosed with recurrent vulvovaginal candidiasis (RVVC) and their partners; and to evaluate the fluconazole (FLZ) susceptibility of the isolates. In a period of six years, among 172 patients diagnosed with vulvovaginal candidiasis, 13 women that presented RVVC and their partners were selected for this investigation. The isolates were obtained using Chromagar Candida medium, the species identification was performed by phenotypic and molecular methods and FLZ susceptibility was evaluated by E-test. Among 26 strains we identified 14 Candida albicans , six Candida duobushaemulonii, four Candida glabrata , and two Candida tropicalis . Agreement of the isolated species occurred in 100% of the couples. FLZ low susceptibility was observed for all isolates of C. duobushaemulonii (minimal inhibitory concentration values from 8-> 64 μg/mL), two C. glabrata isolates were FLZ-resistant and all C. albicans and C. tropicalis isolates were FLZ-susceptible. This report emphasises the importance of accurate identification of the fungal agents by a reliable molecular technique in RVVC episodes besides the lower antifungal susceptibility profile of this rare pathogen C. duobushaemulonii to FLZ.

Environmental isolation, biochemical identification, and antifungal drug susceptibility of Cryptococcus species

Introduction The incidence of opportunistic fungal infections has increased in recent years and is considered an important public health problem. Among systemic and opportunistic mycoses, cryptococcosis is distinguished by its clinical importance due to the increased risk of infection in individuals infected by human immunodeficiency virus. Methods To determine the occurrence of pathogenic Cryptococcus in pigeon excrement in the City of Araraquara, samples were collected from nine environments, including state and municipal schools, abandoned buildings, parks, and a hospital. The isolates were identified using classical tests, and susceptibility testing for the antifungal drugs (fluconazole, itraconazole, voriconazole, and amphotericin B) independently was also performed. After collection, the excrement samples were plated on Niger agar and incubated at room temperature. Results A total of 87 bird dropping samples were collected, and 66.6% were positive for the genus Cryptococcus. The following species were identified: Cryptococcus neoformans (17.2%), Cryptococcus gattii (5.2%), Cryptococcus ater (3.5%), Cryptococcus laurentti (1.7%), and Cryptococcus luteolus (1.7%). A total of 70.7% of the isolates were not identified to the species level and are referred to as Cryptococcus spp. throughout the manuscript. Conclusions Although none of the isolates demonstrated resistance to antifungal drugs, the identification of infested areas, the proper control of birds, and the disinfection of these environments are essential for the epidemiological control of cryptococcosis.

Susceptibility variation of Malassezia pachydermatis to antifungal agents according to isolate source

Malassezia pachydermatis is associated with dermatomycoses and otomycosis in dogs and cats. This study compared the susceptibility of M. pachydermatis isolates from sick (G1) and healthy (G2) animals to azole and polyene antifungals using the M27-A3 protocol. Isolates from G1 animals were less sensitive to amphotericin B, nystatin, fluconazole, clotrimazole and miconazole.

Autophagy enhances NFκB activity in specific tissue macrophages by sequestering A20 to boost antifungal immunity.

Immune responses must be well restrained in a steady state to avoid excessive inflammation. However, such restraints are quickly removed to exert antimicrobial responses. Here we report a role of autophagy in an early host antifungal response by enhancing NFκB activity through A20 sequestration. Enhancement of NFκB activation is achieved by autophagic depletion of A20, an NFκB inhibitor, in F4/80(hi) macrophages in the spleen, peritoneum and kidney. We show that p62, an autophagic adaptor protein, captures A20 to sequester it in the autophagosome. This allows the macrophages to release chemokines to recruit neutrophils. Indeed, mice lacking autophagy in myeloid cells show higher susceptibility to Candida albicans infection due to impairment in neutrophil recruitment. Thus, at least in the specific aforementioned tissues, autophagy appears to break A20-dependent suppression in F4/80(hi) macrophages, which express abundant A20 and contribute to the initiation of efficient innate immune responses.

Immunochip SNP array identifies novel genetic variants conferring susceptibility to candidaemia.

Candidaemia is the fourth most common cause of bloodstream infection, with a high mortality rate of up to 40%. Identification of host genetic factors that confer susceptibility to candidaemia may aid in designing adjunctive immunotherapeutic strategies. Here we hypothesize that variation in immune genes may predispose to candidaemia. We analyse 118,989 single-nucleotide polymorphisms (SNPs) across 186 loci known to be associated with immune-mediated diseases in the largest candidaemia cohort to date of 217 patients of European ancestry and a group of 11,920 controls. We validate the significant associations by comparison with a disease-matched control group. We observe significant association between candidaemia and SNPs in the CD58 (P = 1.97 × 10(-11); odds ratio (OR) = 4.68), LCE4A-C1orf68 (P = 1.98 × 10(-10); OR = 4.25) and TAGAP (P = 1.84 × 10(-8); OR = 2.96) loci. Individuals carrying two or more risk alleles have an increased risk for candidaemia of 19.4-fold compared with individuals carrying no risk allele. We identify three novel genetic risk factors for candidaemia, which we subsequently validate for their role in antifungal host defence.

Susceptibility of Clinical Isolates of Candida to Photodynamic Effects of Curcumin

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

In vitro susceptibility testing of Microsporum gypseum isolated from healthy cattle and soil samples against itraconazole, terbinafine, fluconazole and topical veterinarian drugs

The present study evaluated in vitro susceptibility testing of dermatophytes isolates from healthy cattle and soil samples against three antifungal agents and three topical veterinarian drugs. Itraconazole and terbinafine showed a higher in vitro fungicidal activity than fluconazole. The veterinarian drugs LEPECID (R) and iodine 5% were more active in vitro than the UNGUENTO (R) spray. All drugs showed fungicidal activity against Microsporum gypseum, and they may be considered as efficient agents for the topical treatment of dermatophytoses in cattle.

Susceptibility profile of a Brazilian yeast stock collection of Candida species isolated from subjects with Candida-associated denture stomatitis with or without diabetes

Objective: This study investigated the susceptibility of 198 clinical isolates of Candida species against caspofungin, amphotericin B, itraconazole, and fluconazole. Study Design: Suspensions of the microorganisms were spread on Roswell Park Memorial Institute (RPMI) agar plates. Etest strips were placed on the plates, and the minimal inhibitory concentration (MIC) was read after incubation (48 h at 37°C). Data were analyzed by a factorial analysis of variance and a 2 × 2 post hoc test (α = .05). Results: C glabrata showed the highest MIC values (P < .001) against caspofungin, itraconazole, and fluconazole. For amphotericin B, the MIC values of C tropicalis and C glabrata (P = .0521) were higher than those of C albicans (P < .001). Itraconazole was the least effective antifungal; 93.3% of the C glabrata isolates, 3.3% of the C albicans, and 1.3% of the C tropicalis were resistant. All microorganisms were susceptible to caspofungin and amphotericin B. Conclusions: Caspofungin and amphotericin B should be recommended as an effective alternative for the management of oral Candida infections when treatment with topical or other systemic drugs has definitely failed. © 2013 Elsevier Inc. All rights reserved.

Genetic Separation of FK506 Susceptibility and Drug Transport in the Yeast Pdr5 ATP-binding Cassette Multidrug Resistance Transporter

Overexpression of the yeast Pdr5 ATP-binding cassette transporter leads to pleiotropic drug resistance to a variety of structurally unrelated cytotoxic compounds. To identify Pdr5 residues involved in substrate recognition and/or drug transport, we used a combination of random in vitro mutagenesis and phenotypic screening to isolate novel mutant Pdr5 transporters with altered substrate specificity. A plasmid library containing randomly mutagenized PDR5 genes was transformed into appropriate drug-sensitive yeast cells followed by phenotypic selection of Pdr5 mutants. Selected mutant Pdr5 transporters were analyzed with respect to their expression levels, subcellular localization, drug resistance profiles to cycloheximide, rhodamines, antifungal azoles, steroids, and sensitivity to the inhibitor FK506. DNA sequencing of six PDR5 mutant genes identified amino acids important for substrate recognition, drug transport, and specific inhibition of the Pdr5 transporter. Mutations were found in each nucleotide-binding domain, the transmembrane domain 10, and, most surprisingly, even in predicted extracellular hydrophilic loops. At least some point mutations identified appear to influence folding of Pdr5, suggesting that the folded structure is a major substrate specificity determinant. Surprisingly, a S1360F exchange in transmembrane domain 10 not only caused limited substrate specificity, but also abolished Pdr5 susceptibility to inhibition by the immunosuppressant FK506. This is the first report of a mutation in a yeast ATP-binding cassette transporter that allows for the functional separation of substrate transport and inhibitor susceptibility.

Effects of susceptibility to normative influence and type of testimonial on attitudes toward print advertising

In two experiments, we show how a consumer’s susceptibility to normative influence (SNI) offers useful insights into the effectiveness of two types of testimonials: a typical person endorsement (Study 1) and a celebrity endorsement (Study 2). Specifically, we suggest that two variables moderate testimonial effects—SNI and product attribute information. Results show that in forming their evaluations, high-SNI consumers place a greater emphasis on the testimonial than on the attribute information. In contrast, low-SNI consumers are more influenced by attribute information. A mediation analysis shows that advertising attitudes for high-SNI consumers are mediated by testimonial thoughts, whereas the attitudes for low-SNI consumers are mediated by their attribute thoughts. Theoretical and managerial implications are presented.

The impact of susceptibility to informational influence on the effectiveness of consumer testimonials

In this article we examine how a consumer's susceptibility to informative influence (SII) affects the effectiveness of consumer testimonials in print advertising. More specifically, we show that consumers that are high in SII and that seek consumption-relevant information from other people are more influenced by the strength of the testimonial information than the strength of the attribute information. Conversely, consumers low in SII place greater emphasis on the strength of the attribute information when forming their evaluations. Our results show that consumer psychological traits can have an important impact on the acceptance of testimonial advertising. Theoretical and managerial implications of our findings are discussed.

The susceptibility of digital signatures to fraud in the National Electronic Conveyancing System : an analysis

Public key cryptography, and with it,the ability to compute digital signatures, have made it possible for electronic commerce to flourish. It is thus unsurprising that the proposed Australian NECS will also utilise digital signatures in its system so as to provide a fully automated process from the creation of electronic land title instrument to the digital signing, and electronic lodgment of these instruments. This necessitates an analysis of the fraud risks raised by the usage of digital signatures because a compromise of the integrity of digital signatures will lead to a compromise of the Torrens system itself. This article will show that digital signatures may in fact offer greater security against fraud than handwritten signatures; but to achieve this, digital signatures require an infrastructure whereby each component is properly implemented and managed.