Yongnian Shen

Primary Cutaneous Zygomycosis Caused by Rhizomucor variabilis: A New Endemic Zygomycosis? A Case Report and Review of 6 Cases Reported from China

We report a case of primary cutaneous zygomycosis caused by Rhizomucor variabilis and review 6 cases reported from China that share similar features and are different from those cases caused by other species of Mucorales. It is noteworthy that all 6 of the cases were observed in 3 adjacent provinces of eastern China.

Taxonomy and epidemiology of Mucor irregularis, agent of chronic cutaneous mucormycosis

Mucormycosis usually presents as a progressive infection with significant angio-invasion. Mucormycosis due to Mucor irregularis (formerly Rhizomucor variabilis var. variabilis), however, is exceptional in causing chronic cutaneous infection in immunocompetent humans, ultimately leading to severe morbidity if left untreated. More than 90 % of the cases known to date were reported from Asia, mainly from China. The nearest neighbour of M. irregularis is the saprobic species M. hiemalis. The aim of this study was to evaluate the taxonomic position, epidemiology, and intra- and inter-species diversity of M. irregularis based on 21 strains (clinical n = 17) by multilocus analysis using ITS, LSU, RPB1 and RPB2 genes, compared to results of cluster analysis with amplified fragment length polymorphism (AFLP) data. By combining MLST and AFLP analyses, M. irregularis was found to be monophyletic with high bootstrap support, and consisted of five subgroups, which were not concordant in all partitions. It was thus confirmed that M. irregularis is a single species at 96.1–100 % ITS similarity and low recombination rates between populations. Some geographic structuring was noted with some localised populations, which may be explained by limited air-dispersal. The natural habitat of the species is likely to be in soil and decomposing plant material.

Protothecosis successfully treated with amikacin combined with tetracyclines

We report a case of protothecosis in an 18‐year‐old female student caused by Prototheca zopfii successfully treated with amikacin combined with tetracyclines.

Direct detection and differentiation of causative fungi of onychomycosis by multiplex polymerase chain reaction-based assay

A rapid and reliable triplex PCR procedure was developed to detect pathogenic fungi directly from specimens of onychomycosis. One hundred and four patients were included in this study. Of them, forty-five (43.3%) were finally diagnosed with onychomycosis according to the diagnostic criteria. The sensitivity of PCR, microscopy and culture were 93.3%, 100% and 64.4%, respectively; the specificities were 100%, 86.4% and 100%, respectively; the positive predictive values were 100%, 84.9% and 100%, respectively; the negative predictive values were 95.2%, 100% and 78.7%, respectively. This molecular diagnostic process could distinguish the 3 groups of pathogens in onychomycosis (dermatophyte, yeast and mold) and could be completed within 8 h. This multiplex PCR assay could used in laboratories with no mycological specialization for rapid etiologic diagnosis and treatment selection, especially in suspected fungus cases if they can not be detected by conventional methods or if a rapid diagnosis of onychomycosis is needed.

Multiple cyp51A-based mechanisms identified in azole-resistant isolates of Aspergillus fumigatus from China

ABSTRACT Seventy-two A. fumigatus clinical isolates from China were investigated for azole resistance based on mutations of cyp51A. We identified four azole-resistant strains, among which we found three strains highly resistant to itraconazole, two of which exhibit the TR34/L98H/S297T/F495I mutation, while one carries only the TR34/L98H mutation. To our knowledge, the latter has not been found previously in China. The fourth multiazole-resistant isolate (with only moderate itraconazole resistance) carries a new G432A mutation.

A case of subcutaneous phaeohyphomycosis caused by Cladosporium cladosporioides and its treatment

Phaeohyphomycosis refers to a group of cutaneous, subcutaneous and systemic infections caused by certain dematiaceous fungi characterised by production of melanin in the mycelium. In the past decades, increasing numbers of pathogenic genera causing phaeohyphomycosis have been recognised worldwide, including mainly Exophiala, Phialophora, Cladosporium, Xylohypha, Curvularia, Dactylaria, Exserohilum, Bipolaris, Lecythophora and Alternaria. This communication reports the first case of subcutaneous phaeohyphomycosis due to Cladosporium cladosporioides in China and its pathogenic characteristics.

Oral administration of paeoniflorin attenuates allergic contact dermatitis by inhibiting dendritic cell migration and Th1 and Th17 differentiation in a mouse model

Allergic contact dermatitis (ACD) is a hapten-specific CD4(+) T-cells mediated inflammatory response of the skin. Its pathomechanism involves 2 phases, an induction phase and an elicitation phase. Langerhans cells (LCs) and dendritic cells (DCs) in the skin play key roles in presenting low molecular weight chemicals (haptens) to the lymph nodes. Therefore, inhibition of the migration of LCs or DCs and T-cell proliferation is each expected to control ACD disease. To explore the effectiveness of paeoniflorin (PF) on the migration of LCs and T-cell proliferation in vivo, we establish a murine model of ACD, promoted by repeated exposure to an allergen (specifically 1-Chloro-2,4-dinitrobenzene (DNCB)). Administration of PF inhibits DC migration in this DNCB-induced model in the induction phase. As a result, epidermal LC density in the elicitation phase increased in PF-treated mice when compared to PF-untreated mice. At the same time, PF reduced IFN-γ(+)CD4(+) and IL-17(+)CD4(+) T cells proliferation (but not IL-4(+)CD4(+) T cells proliferation), leading to an attenuated cutaneous inflammatory response. Consistent with this T-cell proliferation profile, secretions of IFN-γ and IL-17 were reduced and IL-10 secretion increased in PF-treated mice, but production of IL-4 and IL-5 remained unchanged in the skin and blood samples. These results suggest that oral administration of PF can treat and prevent ACD effectively through inhibition of DC migration, and thus decrease the capacity of DCs to stimulate Th1 and Th17 cell differentiation and cytokine production.

The Rpd3/Hda1 family of histone deacetylases regulates azole resistance in Candida albicans

OBJECTIVES The histone deacetylase (HDAC) has recently been linked to the morphogenesis and virulence of yeast. However, the effects of HDAC on antifungal susceptibility are not well understood. We sought to characterize the action of histone deacetylation on azole resistance in Candida albicans and its possible mechanism of action. METHODS A total of 40 C. albicans strains were studied. Azole susceptibility with or without trichostatin A (TSA) was determined according to the CLSI microdilution method. The null mutants of HDA1 and RPD3 (genes targeted by TSA) were also investigated using drop-plate assays and a rapid acquisition of adaptation to the azole test. Transcriptional levels of HDAC genes and efflux genes were quantified using RT-PCR for both the basal and fluconazole-induced conditions. RESULTS The inhibition of HDACs by TSA (0.25 mg/L) markedly reduced the trailing growth and the growth of most C. albicans strains. Trailing growth for C. albicans strains was decreased from 2-fold to 256-fold at 48 h. The deletion of HDA1 or RPD3 increased the susceptibility to azoles compared with the WT strain. The expression of HDA1 and RPD3 was up-regulated to different levels, and returned to the level of the susceptible parental strain when stable resistance had formed during the course of acquired fluconazole resistance both in vitro and in vivo. Efflux genes were poorly expressed in mutant strains compared with those of the WT strain. CONCLUSIONS Our results indicate the important role of the Rpd3/Hda1 family in the development of azole resistance in C. albicans. Histone deacetylation may govern the expression of genes related to the early stages of adaptation to azole stress, such as efflux pump genes.

Silenced suppressor of cytokine signaling 1 (SOCS1) enhances the maturation and antifungal immunity of dendritic cells in response to Candida albicans in vitro

Abstract Dendritic cells (DCs) are known to play an important role in initiating and orchestrating antimicrobial immunity. Given the fact that candidiasis appears often in immunocompromised patients, it seems plausible that DCs hold the key to new antifungal strategies. One possibility to enhance the potency of DC-based immunotherapy is to silence the negative immunoregulatory pathways through the ablation suppressor of cytokine signaling suppressor 1 (SOCS1). Here, we deliver small interfering RNA (siRNA) against SOCS1 into murine bone marrow DCs, and as a consequence, we investigate the maturation/action of DCs and the subsequent T cell response after exposure to C. albicans. Our results show that the maturation of DCs (i.e., expressions of CD80, CD40, CD86, and MHC II) are significantly increased in the silenced SOCS1 treatment group after exposure to C. albicans. As a result, suppression of the SOCS1 promotes the greatest expression of IFN-γ and IL-12, and reduces IL-4 secretions, which induce CD4+ cell Th1 differentiation but inactivate Th2 cell development. The responses of IL-6 and TNF-β consist of up-regulation in the presence of C. albicans, but this is not specific to SOCS1 silencing, suggesting that these cytokines are not regulated by the SOCS1 gene in fungal infections. We find Th17 differentiation is unchanged regardless of SOCS1 inhibition. The increase in phagocytosis and killing of C. albicans in SOCS1 gene-treated DCs indicate a role for this cytokine suppressor in innate immunity as well. In conclusion, our findings support the view that SOCS1 protein is a critical inhibitory molecule for controlling cytokine response and antigen presentation by DCs, thereby regulating the magnitude of innate and adaptive immunities by generating IFN-γ-production T cells (Th1)—but not Th17—from naïve CD4+ T cells. Our study demonstrates that SOCS1 siRNA can serve as a useful vehicle to modulate the function of DCs against C. albicans infection.

A new medium for diagnosis of dermatophyte infection

A new medium (DBM) was compared with dermatophyte test medium (DTM) for the diagnosis of dermatophyte infection. The sensitivity was 103 cfu/mL (2 x 101 cfu/slant) for both DTM and DBM with a suspension of Trichophyton rubrum. In axenic cultures, all dermatophytes tested altered the color of both media. Although most non dermatophytic molds made a color change, it was at a slower rate. In nail samples of dermatophyte infection, all dermatophytes altered the color of both media. However, the time for discoloration was shorter with DBM than with DTM (5.83 +/- 0.39 days vs. 7.32 +/- 0.41 days, t = 2.63, P = 0.01). Most isolates of nondermatophyte also made a discoloration, but they could be distinguished from dermatophytes by their colonial diameters when the color began to change (> or = 5 mm). Our results were in good agreement with a professional laboratory of medical mycology, however, the latter is regularly able to differentiate exactly the species of the growing dermatophyte. The DBM medium is more convenient, rapid, more accurate and economical to use than DTM.