bluuebunny/crossref_metadata_2025 huggingface dataset:
P492 Invasive fungal infection during COVID era at tertiary care hospital
Authors: Seema Kumari , Kumar Abhay , Kumar Manoj , Sharma Ashok , Boipai Manju
Published: September 2022

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PM

 

Introduction

Invasive fungal infection is a leading cause of morbidity and mortality in COVID patients as a secondary infection. Invasive fungal infections are often rapidly life-threatening and require specialist consultation for prompt diagnosis and therapy. The reporting of these invasive fungal infections (Mucormycosis, Aspergillosis, and candidiasis) is less than its occurrence.

Objective

This study was undertaken to diagnose invasive fungal infections in COVID patients during the first, second, and third COVID-19 pandemic waves by conventional methods.

Materials and Methods

From March 2020 to December 2020 was considered the first wave pandemic, March 2021 to May 2021 was the second wave pandemic and December 2021 to February 2022 was considered the third wave pandemic era for this region. A total of 42, 168, and 87 samples were collected from patients clinically suspected to have invasive fungal infections during three pandemic waves from Covid indoor patients of RIMS, Ranchi. Among a total 24 were tissue samples, 13 BAL and 260 were nasal swabs/scrapes collected from suspected patients. KOH screening of all samples was done followed by culture on SDA media.

Results

A total of 83/297 (27.94%) cases were positive for KOH screening. In all, 91/297 (30.64%) samples showed culture positivity. A majority of growth was for Mucorales (48.2%), Aspergillus species (24.1%), Candida species (15%), and mixed growth (12.7%). Among Mucorales, Rhizopus was identified in 64% followed by Mucor (28%), Absidia (5%), and Rhizomucor (3%). Among Aspergillus species, majority were A. flavus (48%) followed by A. niger (37%), and A. fumigatus (15%). Maximum positivity for invasive fungal infections was observed during the second wave pandemic (62%) followed by the third wave (27%), and the first wave (11%) respectively.

Discussion

Maximum cases were observed during and after the second wave COVID pandemic era due to excessive use of steroids during COVID treatment and cases were decreased during the third wave as compared with second wave timeframe due to the use of COVID vaccine, and many asymptomatic cases and home quarantine policy.

Conclusion

Early diagnosis and treatment of invasive fungal infections with antifungal therapy and surgical debridement are necessary to reduce mortality and end-organ damage.
P504 Screening of Belgian bats and hibernacula for the description of related fungal microbiomes and the detection of Pseudogymnoascus destructans
Authors: Debergh Hanne , Becker Pierre , Van den Eynde Claudia , Baert Frederik , D'hooge Elizabet , De Pauw Robby , Normand Anne-Cécile , Piarroux Renaud , Stubbe Dirk
Published: September 2022

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PM

 

 

Bats can be affected by fungal pathogens such as Pseudogymnoascus destructans, the causative agent of the white-nose syndrome. Their body surface can also be colonized by fungal commensals or carry transient fungal species and participate in their dispersal. The present study aimed to assess the presence of P. destructans in Northern Belgium, to describe the skin mycobiome of active bats during summer and autumn, and to analyze possible differences in fungal diversity among bat species, sampling sites, and seasons. In total, 114 bat specimens belonging to seven species were sampled from various localities. Culture-based methods revealed an important mycological diversity with 209 different taxa. Overall, a mean of 3.7 taxa per bat was recorded but significant differences were observed between sampling sites and seasons with a higher diversity in autumn as compared to summer. The mycobiomes were dominated by cosmopolitan and plant-associated species, in particular from the genera Cladosporium, Penicillium, and Aspergillus. Other species known to be related to bats or their environment, like Apiotrichum otae, were also retrieved. Although P. destructans was not detected, the sampling of the hibernacula indicated that they can be inhabited by diverse fungal species including a yet undescribed Pseudogymnoascus species, distinct from P. destructans, namely P. cavicola, sp. nov.
S1.3d The human pathobiont Malassezia furfur secreted protease MfSAP1 regulates cell dispersal and exacerbates skin inflammation
Authors: Goh Joleen , Ruchti Fiorella , Poh Si En , Koh Winston L.C. , Tan Kiat Yi , Lim Yan Ting , Thng Steven T.G. , Sobota Radoslaw M. , Hoon Shawn S. , Liu Chenxi , O'Donoghue Anthony J. , LeibundGut-Landmann Salomé , Oon Hazel H. , Li Hao , Dawson Thomas L.
Published: September 2022

S1.3 Malassezia: genetics, genomics, and biology, September 21, 2022, 11:00 AM - 12:30 PM

 

Objectives

Malassezia forms the dominant eukaryotic microbial community on the human skin. The Malassezia genus possesses a repertoire of secretory hydrolytic enzymes involved in protein and lipid metabolism which alter the external cutaneous environment. The exact role of most Malassezia secreted enzymes, including those in interaction with the epithelial surface, is not well characterized.

Methods and Results

In this study, we compared the expression level of secreted proteases, lipases, phospholipases, and sphingomyelinases of M. globosa in healthy subjects and seborrheic dermatitis or atopic dermatitis patients. We observed upregulated gene expression of the previously characterized secretory aspartyl protease MgSAP1 in both the lesional and non-lesional skin sites of affected compared to healthy subjects. To explore the functional roles of MgSAP1 in skin disease, we generated a knockout mutant of the homologous protease MfSAP1 in the genetically tractable M. furfur. We observed the loss of MfSAP1 resulted in dramatic changes in the cell adhesion and dispersal in both culture and a human 3D reconstituted epidermis model. In a murine model of Malassezia colonization, we further demonstrated MfSAP1 contributes to inflammation as observed by reduced edema and myeloid pustule formation with the knockout mutant versus wildtype.

Conclusion

Taken together, we show that this dominant secretory M. aspartyl protease has an important role in enabling a planktonic cellular state that can potentially aid in colonization and additionally as a virulence factor in barrier-compromised skin, further highlighting the importance of considering the contextual relevance when evaluating the functions of secreted microbial enzymes.
S10.4c Successful treatment of mucormycosis in hematological diseases
Authors: Kakeya Hiroshi
Published: September 2022

The diagnosis of mucormycosis relies upon the identification of organisms in tissue by histopathology with culture confirmation. However, culture often yields no growth, and histopathologic identification of an organism with a structure typical of Mucorales may provide the only evidence of infection. PCR-based technique may contribute to the early diagnosis of mucormycosis. We developed a new antigen test. We searched for secreted or membrane-bound proteins of Rhizopus oryzae. Protein RSA (Rhizopus-specific antigen, 23 kDa) was detected at significantly higher concentrations in serum and in lung homogenates of the R. oryzae-infected mice as compared to those of uninfected mice. And we will show a case of hematological disease with diagnosis using RSA test and successful treatment with Liposomal amphotericin B. Our study indicates that protein RSA may be a promising biomarker of R. oryzae infection.
S2.2a African histoplasmosis
Authors: Oladele Rita
Published: September 2022

S2.2 Histoplasmosis and talaromycosis, September 21, 2022, 3:00 PM - 4:30 PM

 

 

African histoplasmosis caused by Histoplasma carpsulatum var dubosii is endemic in Africa with few cases reported from outside Africa usually attributed to travelling or visits to sub-Saharan Africa. The pathogenesis is yet unclear. Infection can be acquired via inhalation of microconidia or by direct inoculation. African histoplasmosis commonly presents with papules, nodules, ulcers, swellings, lymph node enlargement, eczematoid, or psoriosiform skin lesions. Subcutaneous abscesses may also develop with discharging sinuses containing yeast cells of the fungus. Although it is generally believed to be acquired through inhalation, the lungs are usually spared. Disseminated forms are usually characterized by the involvement of bones and other organs including the gastrointestinal tract. As a result of limited availability of diagnostics, data on its prevalence and epidemiology are scarce. As with classical histoplasmosis, African histoplasmosis also mimics other clinical entities including TB and neoplasms. More awareness and a high index of suspicion on the part of clinicians will lead to early diagnosis and invariably improve clinical outcomes. An extensive review of literature revealed 365 cases of African histoplasmosis reported globally; 236 cases from Africa and 38 cases from other geographical regions including an indigenous case report from India; the location of the remaining cases was not found, positive HIV status was found in 75 cases only. No statistically significant relationship was observed when comparing the relationship between positive HIV status and fatal outcomes (P >.05, Fisher's exact test). A case report from the UK mentioned 21 cases of African histoplasmosis previously identified in the region and all were associated with travelling to Africa. Out of the 365 identified cases, diagnostic modality was specified in 264 cases; histopathology (87.9%, n = 232), culture (20.8%, n = 55), microscopy (7.2%, n = 19), serology (2.7%, n = 7), cytology (n = 1, 0.4%), polymerase chain reaction (n = 43, 16.3%), and peripheral blood film (n = 1, 0.4%). Amphotericin B (n = 53), itraconazole (n = 37), and ketoconazole (n = 26) were the predominant antifungals used for treatment. More studies are required to ascertain the true burden and epidemiology of African histoplasmosis and to determine whether these cases reported outside Africa were autochthonous or imported from Africa. Diagnosis by culture, although the gold standard is also not routinely achieved due to lack of biosafety level 3 cabinet especially in resource-limited settings, leading to significant under diagnosis. It is imperative that capacity building and strengthening is instituted to aid the diagnosis and management of African histoplasmosis. There is a need for more studies to ascertain whether there are additional phylogenetic species within the African clade.
S3.2 Challenging clinical cases
Authors: Singhal Tanu , Gopalakrishnan Ram , Soman Rajeev N. , Patel Atul
Published: September 2022

S3.2 Challenging clinical cases, September 21, 2022, 4:45 PM - 6:15 PM

A case of hepato-splenic-renal candidiasis will be discussed with the aim to track down the causative organism and its likely susceptibility. The role of BDG, selection of the antifungal agent, and duration of therapy will be discussed.

 

A case of an HIV-infected patient with cryptococcal meningitis, pulmonary infection, and pulmonary IRIS will be discussed.

 

A case of Candida auris fungemia and organ infection in a liver transplant recipient who developed serially increasing MIC will be presented. The relevance of MIC, tentative breakpoints, and selection of antifungal agents based on PK PD considerations will be discussed.

 

Talamycosis is usually seen in HIV-infected individuals from North East India. Here we discuss a 3-year-old girl with acute lymphoblastic leukemia from Western India who developed cavitary pneumonia and multiple brain abscesses due to talaromyces. The case posed significant management challenges pertaining to both the fungal infection and cancer.

 

Renal mucormycosis in healthy immunocompetent hosts is an entity generally reported only from India and China. We discuss the case of a previously healthy 3-month-old infant who presented with acute renal failure and renal mucormycosis. The case is unique with respect to the source of infection and management strategy.

 

Treatment of fungal infections involving the draining system of the kidney is challenging mainly due to limited antifungal drug penetration at the site of infection. Challenges in the treatment of amphotericin-resistant Aspergillus terreus pelvicalyceal infections will be discussed.

 

CAPA is a well-known complication of coronavirus disease 2019 (COVID-19), but usually involves the lung alone and rarely disseminates when treated. This case illustrates a rare complication of COVID-19, namely endocarditis caused by Aspergillus.

 

Rhinosporidiosis is a well-known disease that usually involves mucosal surfaces in the head and neck. This case illustrates a rare occurrence, namely dissemination to multiple areas and mimicking the clinical presentation of other cutaneous mycoses.
S3.4e Unraveling the role of DOG genes in a novel alternative pathway of glycerol biosynthesis in Candida albicans and its influence on virulence
Authors: Awasthy Chinmayee , Van Genechten Wouter , Himmereich Uwe , Van Dijck Patrick
Published: September 2022

S3.4 Free oral paper session, September 21, 2022, 4:45 PM - 6:15 PM

DOG genes, encoding for 2-deoxyglucose-6-phosphate phosphatase are low molecular weight phosphatases, with an unknown biological function. In contrast to Saccharomyces cerevisiae which has two DOG homologs, C. albicans only has one DOG gene. We hypothesized that DOG1 plays an important role under osmotic or ionic stress by biosynthesizing glycerol, which is known to be vital for biofilm formation and virulence of this pathogenic yeast, via a novel alternative pathway.

 

The known classical pathway of glycerol production begins when the glycolytic intermediate molecule dihydroxyacetone phosphate (DHAP) is converted into glycerol-3-phosphate (G-3-P) by a pair of glycerol-3-phosphate-dehydrogenases, Gpd1 and Gpd2. G-3-P is further dephosphorylated into glycerol by glycerol-3-phosphate-phosphatases, Gpp1 and Gpp2. However, an alternative pathway, where DHAP is dephosphorylated into DHA, which is subsequently converted into glycerol has been proposed, but the enzymes involved in this process have not yet been described. We recently showed that in Saccharomyces cerevisiae, the DOG enzymes are involved in the production of DHA from DHAP, thereby allowing the synthesis of glycerol in the absence of the classical pathway. Overexpression of the DOG genes restored the osmo-tolerance of the gpp1Δ gpp2Δand gpd1Δ gpd2Δ double deletion strains. Furthermore, purified DOG enzymes could also convert DHAP into DHA (Awasthy et al., submitted).

 

Since DOG1 has a potential role in biosynthesizing glycerol via an unconventional route, we are interested to determine its contribution in influencing virulence and biofilm formation in Candida albicans. This putative pathway has been overlooked for the past two decades, leaving behind an evident knowledge gap. We have now generated multiple deletion strains, using CRISPR Cas9, for the C. albicans counterparts of the GPP, GPD, and DOG genes as well as multiple DOG1 overexpression strains in which we observed the restoration of osmotic stress tolerance phenotypically and via growth curves. We also have NMR data showing the accumulation of various metabolites of central metabolism in these strains. Additionally, we have determined the possible role of DOG1 on virulence factors like morphogenesis, adhesion, and biofilm formation in vitro as well as in vivo, the latter with our catheter-based biofilm subcutaneous mouse model system. We also linked DOG1 and its role in glycerol biosynthesis to the survival of C. albicans inside macrophages. Finally, we would be setting up a high throughput small compound screening for this phosphatase as a potential antifungal drug target.
S4.3b Candida glabrata-host interactions
Authors: Hube Bernhard
Published: September 2022

S4.3 Emergent species of the Candida genus, September 22, 2022, 10:30 AM - 12:00 PM

Candida glabrata is among the most common pathogenic yeasts of humans. Yet, this fungus is phylogenetically, genetically, and phenotypically very different from other clinically relevant Candida species. This includes an unusual high level of intrinsic resistance to antifungals such as azoles. Furthermore, in contrast to the rather aggressive pathogenicity mechanisms of the dominant Candida species, C. albicans, C. glabrata seems to have evolved strategies that are based on stealth, evasion and persistence, without causing severe host cell damage during infection. For example, C. glabrata is unable to invade epithelial cells in vitro and causes only low levels of damage in standard in vitro infection models. However, the addition of a single common host protein, albumin, strongly enhances the damage potential to vaginal epithelial cells.

 

Similar to other Candida species, the potential of C. glabrata to survive in human blood is low. However, C. glabrata can survive within macrophages for long periods without causing host cell damage and responses. This intracellular stage requires the acquisition of nutrients, such as biotin, facilitated by defined biotin up-take systems. Survival in macrophages is further supported by transient mitochondria dysfunction: C. glabrata is able to switch into a petite phenotype upon interaction with human phagocytes. The petite phenotype significantly differs from non-petite cells in its growth behavior, its interactions with the immune system, and even its resistance to antifungal drugs. Effectively, the interaction with phagocytes can render C. glabrata mostly resistant to commonly used azole drugs, and vice versa (‘cross resistance’), providing a principle mechanism by which intrinsic antifungal resistance may have evolved.

Sources
S4.5d Comparing the diagnostic performance of the commonly used eumycetoma diagnostic tests using sequencing of the internally transcribed spacer region as the gold standard
Authors: Siddig Emmanuel , Nyuykonge Bertrand , Mhmoud Najwa , Abdallah Omnia , Bahar Mustafa , Ahmed Eiman , Nyaoke Borna , Zijlstra Ed , Verbon Annelies , Bakhiet Sahar , Fahal Ahmed , van de Sande Wendy
Published: September 2022

S4.5 Mycetoma Clinical Trial on fosravuconazole treatment in eumycetoma– Top Line Results, September 22, 2022, 10:30 AM - 12:00 PM

 

Objectives

Mycetoma is a neglected tropical implantation disease caused by 70 different infectious agents. Identifying the causative organism to the species level is essential for appropriate patient management. Ultrasound, histopathology, culture, and two species-specific PCRs are most the commonly used methods for species identification in endemic regions. The aim of this study was to compare the diagnostic performance of these commonly used assays using sequencing of barcoding genes as the gold standard.

Methods

This descriptive cross-sectional study was conducted at the Mycetoma Research Centre, University of Khartoum, Sudan. It included 222 patients suspected of fungal mycetoma caused by Madurella mycetomatis.

Results

In total 154 (69.3%) were correctly identified by ultrasound, histology, culture, and both species-specific PCRs. In 60 patients, at least one of the diagnostic tests failed to identify M. mycetomatis. A total of five patients had no evidence of eumycetoma, and for three, only the ultrasound was indicative of mycetoma. The two species-specific PCRs were the most sensitive and specific methods, followed by culture and histology. Ultrasound was the least specific as it only allowed differentiation between actinomycetoma and eumycetoma. The time to result was 9.38 minutes for ultrasound, 3.76 h for PCR, 8.5 days for histopathology, and 21 days for grain culturing.

Conclusion

Currently, PCR directly on DNA isolated from grains is the most rapid and reliable diagnostic tool to identify M. mycetomatis eumycetoma.
S5.3a Unraveling the genetic determinants of virulence in Cryptococcus neoformans
Authors: Jackson Katrina , Kisakye Diana , Macchietto Marissa , Tiffen Peter , Nielsen Kirsten
Published: September 2022

S5.3 Cellular pleomorphism and fungal virulence, September 22, 2022, 3:00 PM - 4:30 PM

 

 

Cryptococcus neoformans is a human pathogenic basidiomycete yeast that can cause cryptococcal meningitis (CM), predominantly in immunocompromised individuals. The patient outcome depends on both host and pathogen-specific factors, including C. neoformans genetics. A groundbreaking 2012 study was the first to show that patient outcome is associated with genetic differences between C. neoformans isolates. Subsequent population-wide sequencing studies have revealed over 100 sequence types (ST) of C. neoformans that are associated with both geographic location and clinical outcome. All these studies have been broad, examining the severity of disease cryptococcal phenotypes in a collection of highly diverse strains. We chose a narrow focus and collected various genotypic and phenotypic data from a single ST: ST93. ST93 is a common sequence type isolated from patients globally and is the most common clinical isolate found in the sub-Saharan African country of Uganda. Previously, we performed whole genome sequencing on 38 ST93 Ugandan clinical isolates. We identified 652 unique SNPs in this ST93 population compared to the H99 reference genome. We also showed that ST93 contained two subpopulations: ST9A and ST93B. In the current study, we further characterized the genotypic, phenotypic, and virulence differences between these 38 clinical isolates. Using Illumina sequence data, we identified a pattern of linkage disequilibrium that suggested that ST93A and ST93B are evolving separately. We performed long-read sequencing on each isolate to investigate chromosomal changes and large structural variations, allowing us to identify a chromosomal translocation event wherein parts of chromosome 11 had recombined with chromosome 3. Additionally, we characterized several in vitro phenotypes for each isolate and identified three distinct phenotypic clusters based on cell wall challenge and growth experiments. Next, we infected mice with 35 isolates and observed eight different disease manifestations, including isolates that caused non-CNS infections. Overall, by working within a single sequence type, we can gain a deeper understanding of how some small genetic changes can impact strain-specific phenotypes while others have no discernable effect. Eventually, these data can be used to provide valuable information about how each clinical isolate impacts patient outcomes.
S6.2b In vitro susceptibility testing of dermatophytes: toward standardization
Authors: Marie Ditte , Saunte Lindhardt
Published: September 2022

S6.2 Resurgence of dermatophytic infections, September 22, 2022, 4:45 PM - 6:15 PM

Antifungal treatment-resistant dermatophytosis has been known for years1. It has mainly been reported as sporadic cases with clinical failure to a specific antifungal confirmed by in vitro resistance to antifungal compounds determined by antifungal susceptibility testing (AFST). However, in vivo AFST of dermatophytes is not routinely available in most countries, and, therefore, many clinicians solve the problem by changing the antifungal treatment to another drug class hoping that it will result in clinical response. Unfortunately, cross-resistance revealing concomitantly reduced sensitivity to different classes of drugs including terbinafine and azoles have been reported2,3. Furthermore, an increase of antifungal resistant dermatophytosis has been noted mainly in India and other Asian countries4 but sporadic cases have also been registered in the Middle East, Europe, and North and South America suggesting that this may be the top of the iceberg5-8. This stress the need for a standardized AFST, which can be used routinely in order to surveil the disease spread and implement targeted antifungal treatment.

 

Molecular-based methods are able to detect a genetic mutation known to cause antifungal resistance (e.g., mutation in the squalene epoxidase gene)2 whereas culture-based AFST methods are able to determine the minimum inhibitory concentration (MIC) of a given drug for a specific clinical isolate. This should ideally enable to classify the isolate as sensitive, intermediate, or resistant to a specific antifungal agent, but unfortunately, it may be difficult to compare results across studies as the interpretations of MIC results are depending on the AFST method used. Following AFST methods have been used to determine the MIC of dermatophytes: E-test, agar dilution, agar disc diffusion, and macro- and microbroth dilution methods9. They differ in several ways including inoculum concentration, incubation temperature, incubation time, different culture media, and end-point criterion of fungal growth (percentage of growth inhibition)9,10. Standardization is therefore important, and currently, two standardized guidelines for in vitro AFST of dermatophytes exist. One is from the European Committee on Antimicrobial Susceptibility Testing (EUCAST)11 and the other is from the Clinical Laboratory Standards Institute (CLSI)12. Both are using microtiter plates and the EUCAST (E.Def 11.0) guideline has included MIC breakpoints for the classification of whether an isolate is susceptible or resistant to a given drug. Unfortunately, breakpoints are only available for a limited number of dermatophytes and antifungals11.

 

Standardized validated AFST methods will enable us to target the antifungal treatment thereby reducing the risk of ineffective and unnecessary exposure to inappropriate antifungals with potential side effects and reducing the risk of disease spreading.

Sources
S7.3d Environmental surveillance of Aspergillus fumigatus in Dutch agricultural crops
Authors: Zhang Jianhua , de Rooij Bram , leendertse Peter , Zwaan Bas , Schoustra Sijmen
Published: September 2022

S7.3 Emergent theories on pathogenic fungal dispersal around the globe, September 23, 2022, 10:30 AM - 12:00 PM

 

Objectives

Azole-resistant Aspergillus fumigatus isolates from the environment hamper the treatment of patients suffering from Aspergillus diseases due to cross-resistance with agricultural azoles. Previous work has suggested A. fumigatus likely gains resistance through environmental azole exposure in so-called hotspots.

Methods

We investigated A. fumigatus resistance at multi-environmental sites including the compost, strawberry, and potatoes, where farmers used azole fungicides for crop protection.

Results

On average 105 A. fumigatus CFU/g was recovered of which roughly half were itraconazole and tebuconazole resistant. Similar tandem repeat-mediated resistance mechanisms were found in colonies cultured from these environmental sites as reported in clinical azole-resistant isolates.

Conclusions

Our results suggest that not only azole-containing plant-waste material but also other agricultural crops can be hotspots for resistance selection in A. fumigatus and underscores the need to further investigate transmission routes.
S8.3d Characterization of glycosylphosphatidylinositol-linked aspartyl proteases in Candida glabrata: Role in pathogenicity
Authors: Kaur Rupinder
Published: September 2022

S8.3 How the Fungal Cell Wall Glycan Can Modulate the Immune Response?, September 23, 2022, 3:00 PM - 4:30 PM

 

 

Candida glabrata is the second to fourth most common yeast pathogen found in Candida bloodstream infections, depending upon the geographical location. C. glabrata, which belongs to the Nakaseomyces clade, possesses a distinct set of virulence attributes which include the ability to survive and proliferate in macrophages, adhere to biotic and abiotic surfaces and survive a wide range of stresses. Our research is focused on unveiling the strategies that C. glabrata employs to survive the nutrient-poor hostile host environment and evade host immune response. Toward this end, we are delineating the cellular processes, that are regulated by the family of 11 putative glycosylphosphatidylinositol-linked, cell surface-associated aspartyl proteases (CgYapsins, CgYps1-11). We have recently characterized the secretome of C. glabrata wild-type and aspartyl protease-deficient mutant strains, and showed that the GPI-anchored aspartyl proteases are both bonafide constituents and key modulators of the C. glabrata secretome. Further, besides elucidating the role of CgYapsins in the suppression of the host pro-inflammatory immune response, we have identified the flavodoxin-like protein CgPst2 as a substrate of the CgYps1 protease and demonstrated that the CgYps1-mediated cleavage of CgPst2 is pivotal to oligomerization and activity, and functions of CgPst2 in quinone detoxification. These findings underscoring the importance of multifunctional CgYapsins in the physiology and pathogenesis of C. glabrata will be presented.
S9.5d Genotyping of Malassezia species from seborrheic dermatitis/dandruff patients
Authors: Honnavar Prasanna , Chakrabarti Arunaloke , Dogra Sunil , Lakshmi PVM , Rudramurthy Shivaprakash
Published: September 2022

S9.5 Malassezia: pathogenesis and disease, September 23, 2022, 4:45 PM - 6:15 PM

 

Objectives

Seborrheic dermatitis/dandruff (SD/D) are common chronic inflammatory skin disorders characterized by recurrent greasy scales with erythema and itchiness. Malassezia lobose and M. restricta are the predominant agents associated with SD/D. The aim of the study was to differentiate Malassezia strains causing SD/D from commensal using a highly discriminatory DNA fingerprinting technique, Fluorescent Amplified Fragment Length Polymorphism (FAFLP).

Methods

A total of 154 (M. globosa, n = 85; M. restricta, n = 55; M. arunalokei, n = 14; standard strains, n = 3) isolates from SD/D patients and healthy controls were analyzed using FAFLP. DNA sample was digested with restriction enzymes EcoRI and HindIII, and the fragments were linked to prepared adapters. Pre-selective followed by selective amplification reactions were performed using EcoRI-AC [6-carboxyfluorescein (6-FAM) labeled] and HindIII-T selective primers. The similarity coefficient was determined by Pearson correlation with negative similarities clip to zero. The densitometric curve cluster analysis was performed by unweighted pair group method with arithmetic means using Bionumerics software. The similarity co-efficient of 70% was taken as a cut-off.

Results

M. restricta and M. arunalokei isolates had a similarity co-efficient of 20%, whereas it was 50% among M. restricta and 60% among M. arunalokei isolates (Fig. 1). Majority of the isolates (n = 38.69%) clustered to form FAFLP type-I, followed by type-II (n = 14.25%), and type-III (n = 3.6%). All three FAFLP types formed tight clustering among themselves (>80% similarity co-efficient) showing less genetic diversity within each FAFLP type. Type-II clustered strains were isolated from the scalp of SD/D patients (P <.05). M. arunalokei isolates were clustered into two FAFLP types (P = .05). All FAFLP type-I isolates (n = 10,71%) were from the scalp of moderate and severe SD/D patients, whereas all type-II isolates (n = 4,29%) were from nasolabial folds of either SD/D patients or healthy controls. All 11 FAFLP types of M. globosa formed very loose structured cluster showing high genetic diversity in intra and inter-FAFLP types (Fig. 2). Majority of the isolates (n = 63,74%) clustered to form FAFLP type-II, followed by type X (n = 5.6%), type-I (n = 4.5%), type-III (n = 3.3.5%), type-IV (n = 3.3.5%), type-V (n = 2.2%), type-VIII (n = 2.2%), and type-VI, VII, IX, XI (n = 1.1% each). No geographic specific isolate clustering was observed in FAFLP.

Conclusion

M. restricta type-II and M. arunalokei type-I strains were isolated only from the scalp of moderate to severe forms of SD/D. However, no such severity-specific clustering was observed in M. globosa. The results strongly suggest the role of certain genotypes of M. restricta and M. arunalokei in the causation of SD/D.
Liposomal amphotericin B exposure in critically ill patients: a prospective pharmacokinetic study
Authors: Van Daele Ruth , Wauters Joost , Elkayal Omar , Dreesen Erwin , Debaveye Yves , Lagrou Katrien , de Beer Yvo , Maertens Johan , Brüggemann Roger J , Spriet Isabel
Published: September 2022

Liposomal amphotericin B (L-AmB) is a broad-spectrum antifungal drug. Little is known about its pharmacokinetics (PK) in critically ill patients. The aim of this study was to document the PK of L-AmB in this population. It was also explored if covariates may be identified that influence its exposure. All adult, critically ill patients (at the intensive care unit or hematology ward) treated with L-AmB between October 2016 and January 2020 were eligible for this study. The administered dose was left at the discretion of the treating clinician. Plasma samples were collected at predose and 1, 2, 4, 8, 12, 16, 20 and 24 h postdose at an early (day 2–3) and/or later (≥ day 6) treatment day. Additionally, daily trough concentrations were collected until day 14. Of 33 included patients, 31 were evaluable; their median [IQR] age and body weight was 59 [54–64] years and 68 [59–77] kg, respectively. L-AmB was administered at doses between 2.7 mg/kg and 12.3 mg/kg, with a median [IQR] trough concentration of 3.1 [2.0–4.7] mg/l. The overall median area under the 24 h concentration–time curve (AUC0-24) and peak plasma concentration (Cmax) were 169.0 [117.0–253.0] mg h/l and 23.2 [16.9–33.7] mg/l, respectively. A considerable intra- and interpatient PK variability for Cmax and AUC0-24 was observed but no explaining variables, except the administered dose, could be identified. The PK of L-AmB in critically ill patients was documented. A considerable variability in exposure was observed between and within patients; however, it was not associated with a multitude of patient-related characteristics.
Star cluster formation in clouds with externally driven turbulence
Authors: Smith Jamie D , Dale James E , Jaffa Sarah E , Krause Martin G H
Published: September 2022

Star clusters are known to be formed in turbulent molecular clouds. How turbulence is driven in molecular clouds and what effect this has on star formation is still unclear. We compare a simulation setup with turbulent driving everywhere in a periodic box with a setup where turbulence is only driven around the outside of the box. We analyse the resulting gas distribution, kinematics, and the population of stars that are formed from the cloud. Both setups successfully produce a turbulent velocity field with a power-law structure function, the externally driven cloud has a more central, monolithic, clump, while the fully driven cloud has many smaller, more dispersed, clumps. The star formation follows the cloud morphology producing large clusters, with high star-forming efficiency in the externally driven simulations and sparse individual star formation with much lower star formation efficiency in the fully driven case. We conclude that the externally driven method, which resembles a Global Hierarchical Collapse (GHC) scenario, produces star clusters that more closely match with observations.
What powers galactic outflows: nuclear starbursts or AGN?
Authors: Ishibashi W , Fabian A C
Published: September 2022

Galactic outflows can be powered either by nuclear starbursts (SB) or active galactic nuclei (AGNs). It has been argued that extreme starbursts can power extreme outflows, without the need to invoke AGN feedback. However, contributions from past and/or hidden AGN activity cannot be ruled out. Here, we constrain the potential role of the central black hole in driving powerful outflows in starburst galaxies (with no sign of ongoing AGN activity). We examine whether the galactic outflows can be explained by AGN luminosity evolution in the framework of our AGN ‘radiative dusty feedback’ scenario. We show that the outflow energetics of starburst galaxies in the local Universe can be quantitatively reproduced by power-law and exponential luminosity decays, coupled with radiation trapping. Likewise, a combination of heavy obscuration and mild luminosity decay may account for the energetics of galactic outflows observed in dusty star-forming galaxies in the early Universe. We discuss different physical arguments for SB versus AGN outflow-driving, and conclude that the latter can have a major impact on the evolution of galaxies.
Single fluid versus multifluid: comparison between single-fluid and multifluid dust models for disc–planet interactions
Authors: Chan Kevin , Paardekooper Sijme-Jan
Published: September 2022

Recent observations of substructures such as dust gaps and dust rings in protoplanetary discs have highlighted the importance of including dust into purely gaseous disc models. At the same time, computational difficulties arise with the standard models of simulating the dust and gas separately. These include the cost of accurately simulating the interactions between well-coupled dust and gas and issues of dust concentration in areas below resolution of the gas phase. We test a single-fluid approach that incorporates the terminal velocity approximation valid for small particles, which can overcome these difficulties, through modification of FARGO3D. We compare this single-fluid model with a multifluid model for a variety of planet masses. We find differences in the dust density distribution in all cases. For high-mass, gap-opening planets, we find differences in the amplitude of the resulting dust rings, which we attribute to the failure of the terminal velocity approximation around shocks. For low-mass planets, both models agree everywhere except in the corotation region, where the terminal velocity approximation shows overdense dust lobes. We tentatively interpret these as dusty equivalents of thermal lobes seen in non-isothermal simulations with thermal diffusion, but more work is necessary to confirm this. At the same resolution, the computational time for the terminal velocity approximation model is significantly less than a two-fluid model. We conclude that the terminal velocity approximation is a valuable tool for modelling a protoplanetary disc, but care should be taken when shocks are involved.
Impact of subsurface convective flows on the formation of sunspot magnetic field and energy build-up
Authors: Kaneko Takafumi , Hotta Hideyuki , Toriumi Shin , Kusano Kanya
Published: September 2022

Strong solar flares occur in δ-spots characterized by the opposite-polarity magnetic fluxes in a single penumbra. Sunspot formation via flux emergence from the convection zone to the photosphere can be strongly affected by convective turbulent flows. It has not yet been shown how crucial convective flows are for the formation of δ-spots. The aim of this study is to reveal the impact of convective flows in the convection zone on the formation and evolution of sunspot magnetic fields. We simulated the emergence and transport of magnetic flux tubes in the convection zone using radiative magnetohydrodynamics code r2d2. We carried out 93 simulations by allocating the twisted flux tubes to different positions in the convection zone. As a result, both δ-type and β-type magnetic distributions were reproduced only by the differences in the convective flows surrounding the flux tubes. The δ-spots were formed by the collision of positive and negative magnetic fluxes on the photosphere. The unipolar and bipolar rotations of the δ-spots were driven by magnetic twist and writhe, transporting magnetic helicity from the convection zone to the corona. We detected a strong correlation between the distribution of the non-potential magnetic field in the photosphere and the position of the downflow plume in the convection zone. The correlation could be detected 20–30 h before the flux emergence. The results suggest that high free energy regions in the photosphere can be predicted even before the magnetic flux appears in the photosphere by detecting the downflow profile in the convection zone.
VLT/UVES observation of the SDSS J2357−0048 outflow
Authors: Byun Doyee , Arav Nahum , Hall Patrick B
Published: September 2022

We found a broad absorption line (BAL) outflow in the VLT/UVES spectrum of the quasar SDSS J235702.54−004824.0, in which we identified four subcomponents. We measured the column densities of the ions in one of the subcomponents (v = −1600 km s−1), which include O i and Fe ii. We found the kinetic luminosity of this component to be at most $\sim 2.4{{\ \rm per\ cent}}$ of the quasar’s Eddington luminosity. This is near the amount required to contribute to active galactic nucleus feedback. We also examined the time variability of a C iv mini-BAL found at v = −8700 km s−1, which shows a shallower and narrower absorption feature attached to it in previous SDSS observations from 2000 to 2001, but not in the spectra from 2005 and onwards.
Environmental variation of the low-mass IMF
Authors: Tanvir Tabassum S , Krumholz Mark R , Federrath Christoph
Published: September 2022

We use a series of magnetohydrodynamic simulations including both radiative and protostellar outflow feedback to study environmental variation of the initial mass function (IMF). The simulations represent a carefully-controlled experiment whereby we keep all dimensionless parameters of the flow constant except for those related to feedback. We show that radiation feedback suppresses the formation of lower mass objects more effectively as the surface density increases, but this only partially compensates for the decreasing Jeans mass in denser environments. Similarly, we find that protostellar outflows are more effective at suppressing the formation of massive stars in higher surface density environments. The combined effect of these two trends is towards an IMF with a lower characteristic mass and a narrower overall mass range in high surface density environments. We discuss the implications for these findings for the interpretation of observational evidence of IMF variation in early type galaxies.
The global structure of magnetic fields and gas in simulated Milky Way-analogue galaxies
Authors: Wibking Benjamin D , Krumholz Mark R
Published: September 2022

We simulate an isolated, magnetized Milky Way-like disc galaxy using a self-consistent model of unresolved star formation and feedback, evolving the system until it reaches statistical steady state. We show that the quasi-steady-state structure is distinctly layered in galactocentric height z, with a broken power-law structure in Alfven Mach number and plasma beta. Magnetic pressure exceeds turbulent and thermal pressures after the gas is depleted to levels below that of the present-day Galaxy, but is subdominant at higher gas fractions and star formation rates. We find field strengths, gas surface densities, and star formation rates that agree well with those observed in the Solar neighbourhood. The most significant dynamical effect of magnetic fields on the global properties of the disc is a reduction of the star formation rate by a factor of 1.5–2 with respect to an unmagnetized control simulation. At a fixed star formation rate of approximately $2 \, {\rm M}_{\odot }$ yr−1, there is no significant difference in the mass outflow rates or profiles between the magnetized and non-magnetized simulations. Our results for the global structure of the magnetic field have significant implications for models of cosmic ray-driven winds and cosmic ray propagation in the Galaxy, and can be tested against observations with the forthcoming Square Kilometre Array and other facilities. Finally, we report the discovery of a physical error in the implementation of neutral gas heating and cooling in the popular gizmo code, which may lead to qualitatively incorrect phase structures if not corrected.
On the estimation of frequency residuals in a radio occultation experiment
Authors: Tripathi Keshav R , Choudhary R K , Jayalal Lakshmi
Published: September 2022

In the radio occultation (RO) experiments, the difference between observed and predicted Doppler, called frequency residuals, form basic input data to retrieve the vertical profiles of atmospheric parameters. In this paper, we compare different methods to estimate frequency residuals in a one-way downlink single frequency RO experiment, and propose a suitable method that not only improves the residual estimates but is easy to implement too. We show that the Doppler broadening in the received radio signals, which causes uncertainties in Doppler estimation, is predominantly due to changes in the line of sight velocity between the receiver and transmitter during the sampling period. Coupled with the random noises in the receiving system and fluctuations in plasma medium along the propagation path, the resultant uncertainty in Doppler estimates can become as large as 60 Hz. The expected phase changes due to the ionospheric dispersion/refraction, on the other hand, are of the order of 0.01–2 Hz only. To circumvent the issue, we re-sample the observed radio signals in smaller time packets. After removing DC constant shift, a narrow bandpass filter is applied to suppress small-scale fluctuations and Doppler and power of the received signals are estimated. Using Akatsuki radio signals, tracked at Indian Deep Space Network as test data sets, we compare our results with the residuals provided by the Akatsuki team and using the method used for analysing Cassini RO data. We show that our method provides a better estimate of frequency residuals with lesser standard deviations.
Photometry and astrometry with JWST – I. NIRCam point spread functions and the first JWST colour–magnitude diagrams of a globular cluster
Authors: Nardiello D , Bedin L R , Burgasser A , Salaris M , Cassisi S , Griggio M , Scalco M
Published: September 2022

As the James Webb Space Telescope (JWST) has become fully operational, early release data are now available to begin building the tools and calibrations for precision point-source photometry and astrometry in crowded cluster environments. Here, we present our independent reduction of NIRCam imaging of the metal-poor globular cluster M 92, which were collected under Director’s Discretionary Early Release Science programme ERS-1334. We derived empirical models of the point spread function (PSF) for filters F090W, F150W, F277W, and F444W, and find that these PSFs: (i) are generally undersampled (FWHM ∼ 2 pixel) in F150W and F444W and severely undersampled (FWHM ∼ 1 pixel) in F090W and F277W; (ii) have significant variation across the field of view, up to ∼15–20 per cent; and (iii) have temporal variations of ∼ 3–4 per cent across multi-epoch exposures. We deployed our PSFs to determine the photometric precision of NIRCam for stars in the crowded, central regions of M 92, measured to be at the ∼0.01 mag level. We use these data to construct the first JWST colour–magnitude diagrams of a globular cluster. Employing existing stellar models, we find that the data reach almost the bottom of the M 92 main sequence (∼0.1 M⊙), and reveal 24 white dwarf candidate members of M 92 in the brightest portion of the white dwarf cooling sequence. The latter are confirmed through a cross-match with archival HST UV and optical data. We also detect the presence of multiple stellar populations along the low-mass main sequence of M 92.