Paecilomyces lilacinus causing debilitating sinusitis in an immunocompetent patient: a case report

<p>Abstract</p> <p>Introduction</p> <p>Since the discovery of the first documented case of <it>Paecilomyces </it>in 1963, only five cases of <it>Paecilomyces </it>sinusitis have been described to date and all of them have predisposing factors such as immunocompromised status or prior nasal surgery. We present the first case of <it>Paecilomyces lilacinus </it>sinusitis in a fit young woman with no identified predisposing factors. To the best of our knowledge, this is the first known case in the UK and in Europe.</p> <p>Case presentation</p> <p>A 20-year-old Iraqi woman who has lived in the UK for the past five years presented with rhinorrhea, hyposmia, and nasal obstruction. She was previously fit and well and had no significant medical history. Imaging revealed a fungal infection that was eventually revealed on cytological examination to be <it>P. lilacinus</it>.</p> <p>Conclusions</p> <p><it>P. lilacinus </it>is both a difficult and important organism to identify because it has intrinsic anti-fungal resistance. In our case, the infection was severe and recurrent, and the organism demonstrated resistance to common oral anti-fungal agents. There was a delay in its diagnosis, owing to its similarity in appearance to <it>Penicillium </it>and a difficulty in distinguishing between the two without specialized knowledge of fungal taxonomy. In the field of otolaryngology, <it>Paecilomyces </it>is relatively unknown. Our intention is to raise awareness of this organism as well as to describe the challenges in its management.</p

Candida tropicalis antifungal cross-resistance is related to different azole target (Erg11p) modifications

ABSTARCT: Candida tropicalis ranks between third and fourth among Candida species most commonly isolated from clinical specimens. Invasive candidiasis and candidemia are treated with amphotericin B or echinocandins as first-line therapy, with extended-spectrum triazoles as acceptable alternatives. Candida tropicalis is usually susceptible to all antifungal agents, although several azole drug-resistant clinical isolates are being reported. However, C. tropicalis resistant to amphotericin B is uncommon, and only a few strains have reliably demonstrated a high level of resistance to this agent. The resistance mechanisms operating in C. tropicalis strains isolated from clinical samples showing resistance to azole drugs alone or with amphotericin B cross-resistance were elucidated. Antifungal drug resistance was related to mutations of the azole target (Erg11p) with or without alterations of the ergosterol biosynthesis pathway. The antifungal drug resistance shown in vitro correlated very well with the results obtained in vivo using the model host Galleria mellonella. Using this panel of strains, the G. mellonella model system was validated as a simple, nonmammalian minihost model that can be used to study in vitro-in vivo correlation of antifungals in C. tropicalis. The development in C. tropicalis of antifungal drug resistance with different mechanisms during antifungal treatment has potential clinical impact and deserves specific prospective studies

Epidemiology of Invasive Fungal Infections in Latin America

The pathogenic role of invasive fungal infections (IFIs) has increased during the past two decades in Latin America and worldwide, and the number of patients at risk has risen dramatically. Working habits and leisure activities have also been a focus of attention by public health officials, as endemic mycoses have provoked a number of outbreaks. An extensive search of medical literature from Latin America suggests that the incidence of IFIs from both endemic and opportunistic fungi has increased. The increase in endemic mycoses is probably related to population changes (migration, tourism, and increased population growth), whereas the increase in opportunistic mycoses may be associated with the greater number of people at risk. In both cases, the early and appropriate use of diagnostic procedures has improved diagnosis and outcome

Hypermethylation of HOOK2 gene and its relation with Type 2 diabetes susceptibility in individuals with obesity

Failure in glucose response to insulin is a common pathology associated with obesity. In this study, we analyzed the genome wide DNA methylation profile of visceral adipose tissue samples in a population of individuals with obesity and assessed whether differential methylation profiles are associated with the presence of type 2 diabetes (T2D). More than 485,000 CpG genome sites from visceral adipose tissue samples from women with obesity undergoing gastric bypass (n=18), and classified as suffering from type 2 diabetes or not (no type 2 diabetes, NT2D), were analyzed using DNA methylation arrays

Altered intragenic DNA methylation of <i>HOOK2</i> gene in adipose tissue from individuals with obesity and type 2 diabetes

<div><p>Aims/Hypothesis</p><p>Failure in glucose response to insulin is a common pathology associated with obesity. In this study, we analyzed the genome wide DNA methylation profile of visceral adipose tissue (VAT) samples in a population of individuals with obesity and assessed whether differential methylation profiles are associated with the presence of type 2 diabetes (T2D).</p><p>Methods</p><p>More than 485,000 CpG genome sites from VAT samples from women with obesity undergoing gastric bypass (n = 18), and classified as suffering from type 2 diabetes (T2D) or not (no type 2 diabetes, NT2D), were analyzed using DNA methylation arrays.</p><p>Results</p><p>We found significant differential methylation between T2D and NT2D samples in 24 CpGs that map with sixteen genes, one of which, <i>HOOK2</i>, demonstrated a significant correlation between differentially hypermethylated regions on the gene body and the presence of type 2 diabetes. This was validated by pyrosequencing in a population of 91 samples from both males and females with obesity. Furthermore, when these results were analyzed by gender, female T2D samples were found hypermethylated at the cg04657146-region and the cg 11738485-region of HOOK2 gene, whilst, interestingly, male samples were found hypomethylated in this latter region.</p><p>Conclusion</p><p>The differential methylation profile of the <i>HOOK2</i> gene in individuals with T2D and obesity might be related to the attendant T2D, but further studies are required to identify the potential role of <i>HOOK2</i> gene in T2D disease. The finding of gender differences in T2D methylation of <i>HOOK2</i> also warrants further investigation.</p></div

The anthropometric and clinical characteristics of the discovery cohort and the validation cohort.

<p>The anthropometric and clinical characteristics of the discovery cohort and the validation cohort.</p

Altered intragenic DNA methylation of <i>HOOK2</i> gene in adipose tissue from individuals with obesity and type 2 diabetes - Fig 1

<p>A. Hierarchical clustering heatmap. Showing differentially methylated CpGs of autosomal probes from women with obesity and discordant for type 2 diabetes (8 T2D and 10 NT2D). The heat map scale shows the range of methylation values, from 0 (blue) to 1 (yellow). Whether the CpG site analyzed is associated with a CpG island (CGI) or not can clearly be distinguished. Red asterisks mark the differentially methylated probes validated by pyrosequencing on <i>HOOK2</i> gene. B. Strip charts showing β values of three differentially methylated CpGs (dmCpGs) located on <i>HOOK2</i> gene in individual samples of the discovery cohort. The bold dotted line with the rhombus indicates the median value of each group of samples. C. Distribution of differentially methylated CpGs (dmCpGs) relative to CGIs, and relative distribution of dmCpGs across different genomic regions. <i>Abbreviations</i>: <i>T2D (Type 2 Diabetes); NT2D (No Type 2 Diabetes)</i>.</p

Box plots illustrate the methylation values of differentially methylated CpG regions between T2D and NT2D samples validated by pyrosequencing in <i>HOOK2</i> gene.

<p>Schematic representation of the target regions studied and the methylation values from T2D and NT2D samples in the discovery cohort and the validation cohort are shown. Vertical lines represent the location of each CpG site. The analyzed region (blue line) and the CpG sites in the array (red box) are highlighted. The <i>p</i>-values for the comparison of the groups are also indicated (**adjusted <i>p</i>-value <0.05; ***adjusted <i>p</i>-value <0.0001). <i>Abbreviations</i>: <i>T2D (Type 2 Diabetes); NT2D (No Type 2 Diabetes)</i>.</p

Differentially methylated CpG sites in T2D compared with NT2D samples.

<p>Differentially methylated CpG sites in T2D compared with NT2D samples.</p