bluuebunny/crossref_metadata_2025_split huggingface dataset:
P479 Causative agents of Onychomycosis and associated factors: A 15 year study
Authors: Genç Gonca Erköse , Nuriyev Kamran , Küçükkaya Sertaç , Şatana Dilek , Uzun Meltem , Erturan Zayre 
Published: September 2022

Abstract

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM

Objectives
Onychomycosis is a term used to describe nail infections that can cause discoloration, thickening, and separation from the nail bed. These manifestations can cause pain and discomfort and medical intervention may be required. The treatment of this disease is difficult and a time-taking process.
The aim of this study was to determine the frequency and distribution of fungal agents according to age and gender in patients with onychomycosis who applied to our laboratory over a period of 15 years.

Methods
A total of 1337 nail samples, which were sent to the Mycology Laboratory of Istanbul Medical Faculty Hospital, Department of Medical Microbiology between January 2007 and July 2022, were examined with conventional methods.
Calcofluor white and 15% KOH were used for microscopic examination and Sabouraud dextrose agar containing antibiotics with and without cycloheximide was used for culture. Fungi were identified by using conventional methods and/or API, VITEK, or MALDI-TOF MS.

Results
The distribution of 1337 nail samples according to patients’ body region, gender, and age is shown in Table 1. Of the total samples, 945 and 392 were toenails and fingernails respectively. Of the specimens, 1212 (90.6%) were taken from adults and 125 (9.4%) were taken from pediatric patients.
Fungal growth was detected in 139 (11.9%) specimens and one culture showed mixed growth. Yeasts were found to be the most frequent isolated fungi (60.7%) and dermatophytes were at the second place (25.71%). Among yeasts, non-albicans Candida species (76.4%) were found to be more frequent than Candida albicans (17,6%), Trichophyton species were found to be the most frequent dermatophytes (75%). Candida parapsilosis was the most prevalent among identified non-albicans Candida (21.2%). The distribution of fungal agents according to patients’ body region and age is shown in Table 2.
Among the patients with a positive culture, the most frequent underlying comorbidities were diabetes in 16 patients (11.5%) and HIV infection in 4 patients (2.87%). No significant difference was found when culture positivity rates were compared according to age and gender. However, there was a significantly higher rate of culture positivity in fingernails compared to toenails (P &lt; .05).

Conclusion
Onychomycosis agents differ according to regions. In our analyses, we found non-albicans Candida species, especially C. parapsilosis as the most frequent agents of onychomycosis. Because these species are mostly resistant to antifungals this must be kept in mind during therapy.
As comorbidities were only found in a limited number of patients additional studies are needed to find responsible factors.
P493 Functional genomics in Candida glabrata, new tools to study stress, pathogenesis and drug resistance
Authors: Usher Jane 
Published: September 2022

Abstract

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PM
The processes of life are dynamic and changes on a molecular level enable organisms to grow but to adapt and survive in different environments, such as the ability to cause disease within a human host. My research focuses on the human fungal pathogen, Candida glabrata, which can cause illnesses in humans ranging from allergic reactions, infections such as thrush which affects ∼75% of women at least once, to serious diseases in patients that have impaired immune systems. These fungi are increasing in incidence and the reason for this increase is not understood. However, it is clear that the fungus can defend itself against high levels of stress and antifungal drugs used in treatment regimes. My hypothesis is that C. glabrata has evolved the capabilities to withstand a challenge from the combination of environmental and imposed drug stresses.

To look at C. glabrata, I will take advantage of my recent discovery of the sexual cycle in this fungus which offers novel methods to test hypotheses about evolution and pathogenesis. Pathogens of humans, such as C. glabrata, are successful because they adapt effectively to environmental stresses encountered within the host body. Upon recognition by host immune cells, C. glabrata is engulfed and exposed to a combination of stresses. In contrast to other pathogenic fungi, C. glabrata is highly resistant to stress allowing it to survive the host immune defenses. This suggests that resistance to both antifungal drugs and natural host-induced stresses are essential for the establishment and progression of infection. The molecular mechanisms underpinning antifungal resistance and the response to individual stresses have been investigated in isolation, however, little is known about how C. glabrata adapts to combinatorial stresses. The mechanistic explanation of stress adaptation will yield new insights into Candida infection.

Using my newly discovered sexual cycle in C. glabrata, I have generated a series of related strains of the same fungal pathogen that have increased resistance to combinatorial and drug stresses. I will sequence their genomes to identify the critical genes involved in stress resistance and characterize the mechanisms of C. glabrata stress responses. My preliminary data demonstrate that the C. glabrata response to in vitro combinatorial stress is similar to that observed upon phagocyte engulfment. At the level of gene expression, there is an up-regulation of genes encoding functions related to stress adaptation and nutrient recycling overlap. Understanding this regulatory network and the role that selected components (different genes) play in stress resistance, is essential to the development of future drug regimes.
P498 Pneumocystis Jirovecii pneumonia: Clinical profile and diagnostic modalities
Authors: Tarai P Bansidhar 
Published: September 2022

Abstract

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

Objectives
In developing countries like India, the diagnosis of Pneumocystis jirovecii infection is often made either by conventional staining or clinically. This study was planned to know the utility of polymerase chain reaction (PCR) in diagnosing Pneumocystis jirovecii pneumonia (PJP), to compare the PCR results with that of the staining technique, and also to correlate the results with the radiological condition of patients from a tertiary care center in India.

Method
A retrospective study included 3500 adult in-patients with symptoms of lower respiratory tract infection. Sputum and bronchoalveolar lavage samples were proceeded for both staining and PCR for multicopy mtLSU gene and singlecopy DHPS fas gene of P. jirovecii.

Results
The present study was carried out in the Department of Microbiology, Max, Hospital, Saket, New Delhi, India. Between the years 2019 and 2022, the patients with clinically suspected pneumocystis pneumonia who attended outpatient or admitted to the Departments of Medicine, Gastroenterology, and Neurology, etc. of our hospital were retrospectively analyzed. The details of these patients were analyzed as per a well-structured proforma that included the detailed clinical history and laboratory data from the hospital records. A total of 3500 patients were included in the present study. Of these 3500 patients, 1.42% (50/3500) patients of pneumocystis pneumonia were confirmed, based on positivity by at least any two of the above-mentioned techniques. The age of the patients ranged from 29 to 80 years (mean 32 years). Among these 50 patients, 34 (68%) were males and 16 (32%) were females and the male-to-female ratio was 2:1. A total of 10 patients had human immunodeficiency virus (HIV) infection, while the other 25 were HIV negative. The immune status of five patients was unknown. Fever and dyspnea (n = 44, 88%), non-productive cough and abnormal auscultation sound (n = 30, 60%), and also chills and weight loss (n = 10, 20%) were the documented clinical symptoms of PJP. Radiological diagnosis of Pneumocystis pneumonia was noticed in 34 cases. Foamy alveolar casts were present in 19 cases. Silver methenamine stain enhanced the rounded, helmet, or cleft forms of sporozoites. Inflammatory infiltrate was mainly polymorphonuclear. All the cases were confirmed as P. jiroveci by PCR amplification.

Conclusion
Clinicians often face the diagnostic dilemmas presented in the study. Individual modalities of the diagnosis are available, but all have drawbacks with varied sensitivity and specificity. Combining the available clinical, radiological, and microbiological modalities to reach early diagnosis can go a long way to avoid misdiagnosis and unnecessary delays in treatment.
S1.5c Proteomics in fungal keratitis research: a road map to personalized treatment
Authors: Prajna Lalitha 
Published: September 2022

Abstract

S1.5 Mycotic Keratitis, September 21, 2022, 11:00 AM - 12:30 PM
Research becomes very significant and meaningful when it addresses a significant public health problem of a region. Fungal keratitis, ulceration of the cornea due to fungal infection, is one such serious problem. This infection that results in monocular blindness affects primarily the agrarian population and is considered to be a silent epidemic in India.

The current treatment for fungal keratitis is the topical application of antifungal drugs such as natamycin and voriconazole. Nearly 40% of the patients do not respond to this treatment and require corneal transplantation. Treatment with antifungal drugs is not a holistic approach as it addresses only killing the fungus. The exaggerated inflammatory response at the site of infection may be a crucial factor in the disease outcome. And, this is not taken into account during the treatment due to the lack of knowledge of the host response during the fungal infection. This was the starting point of our research in fungal keratitis—to understand the corneal immune response to fungal infection.

Using mass-spectrometry-based proteomics studies on a tear from keratitis patients, we identified that in response to the fungal infection, the complement and coagulation pathways were activated along with neutrophil-mediated defense responses, notably the neutrophil extracellular traps. These pathways and their cross-talk with each other were primarily responsible for the exaggerated immune response at the site of infection. We selected five tear proteins that were significantly altered and validated them to serve as indicators of the inflammatory status of the ulcer in keratitis patients. Further, we developed a predictive logistic regression model that incorporates tear biomarker levels and ulcer characteristics to identify the subset of patients who are unlikely to respond to the antifungal treatment. We are currently exploring the possibility of using tear-derived EVs or their cargo as adjuvant therapy to modulate the inflammatory response in these non-responder patients.

Through our efforts using proteomics approaches, we now have five tear proteins as indicators of the inflammatory status in keratitis patients. These proteins along with the clinical features can identify the subset of patients who are unlikely to respond to antifungal treatment. Additionally, we showed that keratitis patient tear-derived extracellular vesicles are enriched with proteasomes. As proteasomes have an established role in immune modulation, EVs with proteasomes are thus promising candidates for adjuvant therapy, which we are currently exploring. Thus, our journey of over a decade of research on fungal keratitis started with the basic research to understand the host response that in turn provided the leads for translational research, which is now advancing towards personalized treatment for these patients.
S2.4d Combination antifungal effects of eugenol with voriconazole against Candida tropicalis and Candida krusei strains isolated from the genital tract of mares
Authors: Sharifzadeh Aghil , Shokri Hojjatollah , Nikaein Donya 
Published: September 2022

Abstract

S2.4 Veterinary mycology research, September 21, 2022, 3:00 PM - 4:30 PM

Objectives
The objective of the current study was to investigate the possibility that eugenol synergizes the antifungal effects of voriconazole on genital isolates of Candida krusei and Candida tropicalis from mares.

Methods
The antifungal activity of eugenol and voriconazole was evaluated using the broth microdilution assay (CLSI- M27-A3). The synergism of eugenol and voriconazole against genital Candida isolates was evaluated by the microdilution checkerboard method.

Results
Minimum inhibitory concentration (MIC) values for eugenol and voriconazole ranged from 400 to 800 μg/ml and 1 to 8 μg/ml, respectively, for C. tropicalis isolates, and from 200 to 400 μg/ml for eugenol and 2 to 16 μg/ml for voriconazole against C. krusei isolates. Eugenol decreased the arithmetic mean of MIC for voriconazole against C. tropicalis and C. krusei isolates from 2.66 to 0.46 μg/ml and 7.77 to 0.41 μg/ml respectively. The fractional inhibitory concentration index (FICI) values for the eugenol voriconazole combination ranged from 0.25 to 0.88 and 0.19 to 0.63 for C. tropicalis and C. krusei isolates respectively. A synergistic effect of eugenol in combination with voriconazole was observed for 83.3% of C. tropicalis and 77.7% of C. krusei isolates. The antagonistic activity was not seen in any of the isolates tested.

Conclusions
Eugenol showed fungistatic and fungicidal effects against genital Candida isolates and, in combination, synergized the antifungal effects of voriconazole. The eugenol-voriconazole combination can lay the foundation for a therapeutic approach against isolates in which azole resistance has increased over time.
S3.4d The role of NLRP3 inflammasome in host defense during Talaromyces marneffei infection
Authors: Sha Lu , Jinquan Wu , Liyan Xi , Zhou Xin 
Published: September 2022

Abstract

S3.4 Free oral paper session, September 21, 2022, 4:45 PM - 6:15 PM
Talaromyces (Penicillium) marneffei (T. marneffei) is the only thermally dimorphic pathogen in Talaromyces. The pathogenesis of T. marneffei in mammals is not yet fully understood. Inhalation of T. marneffei conidia without normal clearance may result in conidia dissemination throughout the body and lead to disseminated infection. In TSM patients, study have shown that IL-1β and IL-18 levels increased and were consistently associated with the severity of sepsis and outcomes of post-treatment. That means poor outcome likely was associated with an overly strong immune response. Several studies have identified inflammasome activation as an essential immune response in host defense against fungal pathogens. Among them, NLRP3 inflammasome is the most widely characterized. However, the role of NLRP3 inflammasomes in T. marneffei-induced immunopathology remains to be elucidated. Therefore, in the present study, we aimed to address the role played by the NLRP3 inflammasome in the T. marneffei systemic infection in mice.

We established T. marneffei infected murine pulmonary model with two groups of mice, including the Nlrp3-/- mice and wild-type mice.

We found that infected mice displayed NLRP3 inflammasome activation and increased production of IL-1β upon pulmonary T. marneffei infection. Further, we demonstrated that T. marneffei conidia activated the NLRP3 inflammasome both in mice and human macrophages. And T. marneffei conidia induced IL-1β released by infected macrophages is NLRP3 inflammasome-dependent. In vivo study, we found that NLRP3 contributes to the development of lethality in the early stage of pulmonary T. marneffei infection. However, Nlrp3-/- mice showed a similar fungal load to the WT in the middle stage of infection and a significantly increased number of fungi recovered from the lung of the WT mice could be seen in the late stage of infection. Moreover, NLRP3 contributes to pathogenic inflammation in pulmonary T. marneffei infection and contributes to neutrophil recruitment and pulmonary injury.

So, in the present study, we demonstrated that the NLRP3 inflammasome is activated during T. marneffei infection. But NLRP3 inflammasome plays a dual role during pathogenic T. marneffei: an early inflammatory response inducing a protective environment, and a subsequent excessive damaging inflammatory response that contributes to pathogenesis and mortality. This study identifies for the first time that activation of the inflammasome in the later stages of TSM detrimentally contributes to pathogenesis and suggests that targeting the inflammasome may be a therapeutic option to treat pathogenic T. marneffei infections.
S3.5a Contamination in sand and water of sea, lakes, and river beaches: Risk factor for fungal human disease
Authors: Segal Esther 
Published: September 2022

Abstract

S3.5 Environmental exposure - risk for human fungal disease, September 21, 2022, 4:45 PM - 6:15 PM
Marine and freshwater bodies, such as rivers and lakes are known as possible niches harboring microbes that may affect human health.

These ecosystems have been extensively researched, and even regulated, for the presence of bacterial contamination.

Fungal contamination has been less researched and lacks regulation, notwithstanding the recent finding that the antifungal resistant yeast species Candida auris has been isolated from a marine ecosystem.

The present lecture will focus on a recent collaborative study, involving 13 countries, spanning from the Atlantic to the Eastern Mediterranean coasts, and including the Italian lakes and the Adriatic, Baltic, and Black Seas. The study explored fungal contamination of sand and water of the sea, lakes, and river beaches in 91 bathing sites, and water of 67 of these.

This study considered several fungal parameters: all fungi, several species of the genus Aspergillus and Candida, plus other yeasts, allergenic fungi, Dematiaceous fungi, and dermatophytes. The study took in account four variables that might influence the results of the analytical parameters, such as: (1) coast or inland location, (2) urban and non-urban sites, (3) period of the year, and (4) geographical proximity and type of sediment.

A site-blind median was found to be 89 Colony-Forming Units (CFU) of fungi per gram of sand in coastal and inland freshwaters, with variability between 0 and 6400 CFU/g. For freshwater sites, that number was 201.7 CFU/g [0, 6400 CFU/g (P = .01) and for coastal sites was 76.7 CFU/g (0, 3497.5 CFU/g)]. For coastal waters and all waters, the median was 0 CFU/ml (0, 1592 CFU/ml), and for freshwaters 6.7 (0, 310.0) CFU/ml (P &lt;.001). The fungal load in water has to be further corroborated in additional ongoing studies.
Some of these will be presented herewith.

The lecture will also include, as an example, the data collected at the Israeli Mediterranean coast. This study included a screen of sand and water of six urban beaches, from north to south of the Israeli Mediterranean Coast. Sand samples were extracted by water, and the water wash was cultured and quantitated. Water samples were quantitated as well. The fungi were identified phenotypically, by MALDI-TOF MS system and ITS sequencing. The screen revealed that about 80% of the isolates were molds and about 20% yeasts. The mold species included opportunistic pathogens and potential allergens: Aspergillus fumigatus, Fusarium, Penicillium, and Mucorales species. Yeast isolates included Candida, Cryptococcus and Rhodotorula species. The collaborative study and the example study confirmed the relevance of all variables for some of the fungal parameters. The results suggest that beaches should be monitored for fungi for safer use and better management, and for the benefit of public health.
S5.3b Fungal spores: Initiators of colonization and infection
Authors: Baltussen Tim , Brule Tom van den , Dijksterhuis Jan 
Published: September 2022

Abstract

S5.3 Cellular pleomorphism and fungal virulence, September 22, 2022, 3:00 PM - 4:30 PM
Fungi produce asexual and sexual spores for reproduction and distribution, which can be both in space and time. Distribution in space occurs, by air movement, but also, by water or other vectors such as living organisms. Filamentous fungi from the division Ascomycota that belong to the order Eurotiales produce asexual spores called conidia. Conidia are moderately stress-tolerant cells and are able to survive unfavorable conditions such as thermal stress, dehydration, osmotic pressure, oxidative stress, variations in pH, and UV. For example, conidia of the fungus Penicillium chrysogenum are isolated worldwide and must be regarded as cosmopolitan. In many cases, conidia might ‘land’ closely to the location of production, but still many spores making into the higher air layers. There is indirect evidence that spores may be able to travel large distances through the air. For example, Aspergillus sydowii conidia have been suggested to travel over thousands of kilometers from the Sahara Desert to the Caribbean reefs.

Distribution in time is occurring as stress-resistant cells remain dormant at one location for an extended period, awaiting conditions that are more favorable for growth. Some ascospores (sexual spores) are extremely stress-resistant and dormant for very long periods. Other species show extended dormancy in a dried state. As microbial species are inherently variable, stress resistance varies between strains from the same species. For example, conidial heat resistance (D60) of various strains of the fungus Paecilomyces variotii ranged between 3.5 to 27.6 min. This intraspecific variation could have profound consequences on diagnostics, virulence, and antifungal treatment in clinical settings.

For conidial germination in most filamentous fungi, the presence of nutrients such as inorganic salts, sugars, and amino acids is required. The swelling phase of conidia is also called isotropic growth. Swollen conidia direct the growth to one side of the cell to grow in a polarized fashion, which leads to the formation of a germ tube (polarized growth). There is a notable drop in stress resistance during isotropic and polarized growth and genes expressed during these stages might represent novel targets for fungal infection.