Medical mycology journal最新文献

{"title":"P010 Evaluation of antifungal efficacy of two novel cyclic lipopeptides of the class Bacillomycin from Bacillus subtilis RLID 12.1 in a murine model of invasive candidiasis","authors":"N. Kashyap, R. Paul, S. Rudramurthy, U. Roy, H. Kaur, Anup K. Ghosh, A. Chakrabarti","doi":"10.1093/mmy/myac072.P010","DOIUrl":"https://doi.org/10.1093/mmy/myac072.P010","url":null,"abstract":"Abstract Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM Objective To evaluate the in vivo efficacy of HPLC–purified antifungal lipopeptides (AF4 and AF5) in a murine model of disseminated candidiasis. Methods C. albicans AMR16294 isolate was used for all the in vivo experiments. A total of 6-week-old pathogen-free, female BALB/c mice, weighing 20-25 g were used for all animal experiments. For Kaplan-Mier analysis, mice were rendered neutropenic by a loading dose of 200 mg/kg cyclophosphamide three days prior (D-3) to infection and 150 mg/kg (D + 1) maintenance dose on day 1 post-infection (D + 1). A total of 60 mice were randomized into 8 different groups with 5 or 6 animals in each group. Animals were infected with 100μL of ∼ 1 × 10⁵ blastospores (corresponding to LD90) via the lateral tail vein. AF4 and AF5 were formulated in sterile PBS and administered intraperitoneally at doses of 5 mg/kg and 10 mg/kg body weight and compared with a clinically-relevant human equivalent dose of caspofungin. AF4, AF5, caspofungin, or vehicle were administered at 1 h and 24 h post-infection. The survival of the mice was monitored for 14 days post-infection. For organ fungal-burden assessment, mice from each group were euthanized by CO2 inhalation, and the organs were aseptically removed, homogenized, and cultured on SDA. Results Both the doses of AF4 significantly reduced the mortality of mice compared to vehicle-treated mice. The survival over 2 weeks in 5 mg/kg, 10 mg/kg, and caspofungin arms were similar and no death was reported in the three groups (P <.01). In contrast, the mortality in-vehicle- administered group was 80% with a median survival of 8 days. A similar survival benefit was observed in AF5-treated mice. While the median survival in the vehicle-treated arm was 5 days, the 2-week survival in 5 mg/kg and 10 mg/kg arms was 80%-100%, comparable to that in the caspofungin arm (P <.01) (Fig. 1). The median CFU/g kidney tissue in 5 mg/kg arm of AF4 was 1.3 × 10⁴ equivalent to a 4-log reduction compared to the vehicle arm (3.8 × 10⁸ CFU/g kidney, P <.0001). The in vivo efficacy was higher at a higher dose with the kidney homogenates of 10 mg/kg arm yielding sterile cultures comparable to that of CAS arm (Fig. 2). Similar organ fungal-burden reduction was noted in heart and splenic tissues with a median cfu/g tissue of 1.3 × 10⁴ in 10 mg/kg, while CAS arms yielded sterile cultures. In AF5 treated groups, the median cfu/g kidney tissue in 5 mg/kg arm was 1.3 × 10⁴, however, the heart and splenic tissue homogenates yielded less fungal burden with median (q2) cfu/g as 0, while q3 of 6.7 × 10³and 1.3 × 10⁴, respectively (Fig. 2). Conclusion Both the antifungal compounds demonstrated a remarkable in vivo efficacy against C. albicans with a significant improvement in survival and a reduction in the organ-fungal burden.","PeriodicalId":18325,"journal":{"name":"Medical mycology journal","volume":"66 1","pages":""},"PeriodicalIF":1.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72535708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P051 A case of recalcitrant sporotrichosis by infection of Sporothrix globosa","authors":"Eun-seon jeong, J. Yim, H. Kwon, J. Choi, Dong-Yeon Shin, Jayoung Kim","doi":"10.1093/mmy/myac072.P051","DOIUrl":"https://doi.org/10.1093/mmy/myac072.P051","url":null,"abstract":"Abstract Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM Objectives Sporotrichosis is the leading subcutaneous mycosis caused by the Sporothrix (S.) schenckii complex. S. globosa is the causative organism of fixed sporotrichosis in Korea. The preferred regimen of cutaneous sporotrichosis is itraconazole for 3-6 months, however, there were few studies for recalcitrant sporotrichosis. Methods In 2018, we performed a histological examination of a patient who suffered sporotrichosis for 3 years and cultured part of the specimen. Despite various regimens for years, improvement and exacerbation were repeated, so we took another skin biopsy and cultured it in 2021. Isolates from the 2018 and 2021 lesions were identified as S. globosa by ribosomal DNA ITS sequencing (GenBank accession number: MH499862 and MH499863). The in vitro antifungal sensitivity tests were performed by broth microdilution method according to CLSI M38-A2 guidelines or Sensititre YeastOne® manufacturer's instructions. They were incubated at 30°C in a non-CO2 incubator for 7 days. Results In 2018, histologically, we observed chronic inflammatory granuloma comprising lymphocytes, histiocytes, and giant cells, and several spores with periodic acid-Schiff (PAS) staining. Microscopic findings and ITS sequences of rRNA gene were identical with S. globosa. The antifungal susceptibility profile in 2018 revealed sensitive to terbinafine (0.125 μg/ml), and moderate to high MIC values for amphotericin B (2 μg/ml), itraconazole (>16 μg/ml), voriconazole (>16 μg/ml), and echinocandins (>16 μg/ml). Treatment with terbinafine, itraconazole, or amphotericin B, the skin lesions were partially improved, but were not cured. In 2021, we took another skin biopsy and culture specimen. Histopathological and mycological examination results were the same as before. The antifungal susceptibility profile revealed sensitive to itraconazole (0.5/ml), and high MIC for others. Clinically, skin lesions were not improved with the use of itraconazole 200 mg/d. Itraconazole 400 mg/d with local heating induced moderate improvement. There was no evidence of immune deficiency. Conclusion We experienced recalcitrant sporotrichosis that did not respond to itraconazole and terbinafine, and the sensitivity of antifungal was changed. In this case, the combination treatment including local heating, saturated KI may be considered, and frequent antifungal susceptibility tests are needed.","PeriodicalId":18325,"journal":{"name":"Medical mycology journal","volume":"6 1","pages":""},"PeriodicalIF":1.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72641838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P365 Upsurge of Mucormycosis in COVID-19—a retrospective study in a tertiary care hospital in Punjab","authors":"S. Mohan","doi":"10.1093/mmy/myac072.P365","DOIUrl":"https://doi.org/10.1093/mmy/myac072.P365","url":null,"abstract":"Abstract Poster session 3, September 23, 2022, 12:30 PM - 1:30 PM Objectives Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been linked to a variety of opportunistic bacterial and fungal infections. Mucorales have been reported as the main fungal pathogens to exist as co-infection with COVID-19. Factors that contribute to a higher incidence of Mucormycosis or Mucorales to germinate in COVID-19 patients are high glucose levels in their blood (diabetes, steroid-induced hyperglycemia), low oxygen content (hypoxia), high iron levels, and decreased phagocytic activity of neutrophils due to immunosuppression because of cytokine storm in SARS-CoV-2 infection. Mucormycosis is an angioinvasive disease caused by order Mucorales and genus Rhizopus, Mucor, Rhizomucor, Cunnighamella, and Lichthemia. The most common species amongst all is Rhizopus arrhizus which is responsible for 90% cases of Rhino-Orbital Cerebral form and accounts for 60% cases of mucormycosis cases in India. Methods A retrospective study was conducted at Christian Medical College and Hospital, Ludhiana from May 1, 2021 to February 28, 2022 for a duration of 10 months. Most of the samples obtained were necrotic bone/tissue or mucosa from the rhino-cerebral part. The obtained sample was inoculated on Sabouraud's Dextrose Agar (SDA) at 22°C as well as 37°C followed by 40% KOH examination. The tubes were routinely checked once in a week and Lactophenol Cotton Blue (LPCB) preparation was made from teasing the isolate once it becomes culture positive. Results Total 29 samples were smear-positive for broad, sparsely septate hyphae in KOH examination under the microscope. Out of those 29 cases, 18 (62.06%) patients were COVID-19 positive (either RTPCR positive, TrueNat PCR positive, or Rapid Antigen positive), 5 patients were COVID-19 negative and COVID-19 testing was not done in 6 patients. Out of 29 smear-positive cases, 17 (58.62%) were culture positive for Mucorales, 7 (24.13%) grew contaminants namely Aspergillus species (mainly Aspergillus flavus), Penicillium species, bacterial contamination, and 5 (17.24%) were culture negative. Amongst 17 cases of Mucorales, 9 (52.94%) were Rhizopus species, 6 (35.29%) were Mucor species and 2 (11.76%) were Rhizomucor species. Amongst the culture-positive cases for Mucorales, 13 (72.22%) cases were COVID-19 positive. Conclusion COVID-19 has thrown the entire globe into chaos, and there is still no specific cure for this viral illness. Patients are susceptible to secondary fungal infections such as Mucormycosis as a result of the infection, immunosuppression, previous comorbidities, and medicines. Mucormycosis infection is severe because of its rapid disease progression and angioinvasive nature. As a result, researchers and healthcare practitioners should take immediate steps to control this mucormycosis infection by understanding its impact and severity, particularly in COVID-19 patient","PeriodicalId":18325,"journal":{"name":"Medical mycology journal","volume":"18 1","pages":""},"PeriodicalIF":1.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79859547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P118 Pentraxin-3 interacts with Aspergillus fumigatus conidia to regulate pro-inflammatory cytokine production","authors":"S. Dellière, S. Wong, C. Chauvin, J. Bayry, A. Carvalho, A. Inforzato, V. Aimanianda","doi":"10.1093/mmy/myac072.P118","DOIUrl":"https://doi.org/10.1093/mmy/myac072.P118","url":null,"abstract":"Abstract Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM Objectives Long pentraxin-3 (PTX3) is a soluble pattern-recognition receptor secreted by phagocytes and non-immune cells at sites of inflammation. It has been reported to have a nonredundant role in the immune response against Aspergillus fumigatus. Indeed, PTX3 knock-out mice show an increased susceptibility to invasive pulmonary aspergillosis (IPA) with a higher mortality rate. In humans, PTX3 genetic deficiency or single nucleotide polymorphism has also been associated with an increased risk of IPA. However, the way in which PTX3 interacts with A. fumigatus and its mechanism of action has yet to be elucidated. The aim of the study was to investigate potential A. fumigatus ligands for PTX3 and the impact of A. fumigatus opsonization by PTX3 on modulating the immune response. Methods Aspergillus fumigatus conidia, the infective morphotype, were incubated with PTX3 with or without human serum, stained with anti-PTX3 antibody, and studied by immunofluorescence. Identification of potential fungal ligands for PTX3 was performed by ELISA. Fixed conidia and germinated conidia were opsonized with different serum factors and co-incubated with human monocyte-derived macrophages (hMDM) for 24 h at 37°C. Culture supernatants were collected, and pro-/anti-inflammatory cytokines were measured by sandwich ELISA. Results PTX3 did not bind A. fumigatus conidia directly but in the presence of human serum, purified collectins [surfactant protein D (SP-D) or C1q], and complement products (C3b). Pre-opsonization of conidia with these complement proteins or SP-D stimulated proinflammatory cytokine secretion by hMDM upon interaction (Fig. 1a). In contrast, secondary opsonization of complement proteins or SP-D opsonized conidia with PTX3 significantly reduced pro-inflammatory cytokines and increased anti-inflammatory cytokine secretion from hMDM. PTX3 opsonized PFA-fixed germinating conidia significantly reduced pro-inflammatory cytokine and increased anti-inflammatory cytokines secretion from hMDM (Fig. 1b). Conclusion PTX3 is an acute phase protein expressed in response to pro-inflammatory stimuli during infection and that is increased in bronchoalveolar lavage of patients with aspergillosis. Our recent data with A. fumigatus suggest that PTX3 is an immunoregulatory protein that reduces pro-inflammatory response. Although an inflammatory response is necessary to fight against fungal pathogens, the tissue damage associated with enhanced inflammation can be deleterious and facilitate A. fumigatus infection.","PeriodicalId":18325,"journal":{"name":"Medical mycology journal","volume":"141 1","pages":""},"PeriodicalIF":1.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80564472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P133 Post-COVID-19 recurrent fungal urinary tract infections: A case series","authors":"Siddhant Shetty, U. Agrawal, M. Kruthi, Amar Kardale, Camilla Rodrigues, V. Joshi, A. Hegde, A. Sunavala","doi":"10.1093/mmy/myac072.P133","DOIUrl":"https://doi.org/10.1093/mmy/myac072.P133","url":null,"abstract":"Abstract Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM Background COVID-19 has opened a pandora's box of opportunistic infections and immune alteration. We hereby present a series of patients with recurrent fungal urinary tract infections triggered by an episode of COVID-19. Description Case 1: A 66-year-old male, diabetic, known chronic kidney disease, had moderate COVID-19 in September 2020 needing remdesivir and steroids; 2 months later, he was treated for a fungal UTI elsewhere. In May 2021, he presented with right-sided pyelonephritis, hydroureter, and pyonephrosis. DJ stenting was done and cultures grew C. tropicalis. Record of anti-fungal susceptibility from the fluconazole resistance and was hence treated with 21 days of micafungin with significant improvement. Despite 3 weeks of directed anti-fungal treatment, he had recurrent episodes of candiduria with azotemia. Cystoscopy and selective sampling yielded C. tropicalis from the right pelvi-calyceal system, but as he was unwilling for nephrostomy and local antibiotic instillation he was started on anidulafungin and long-term 5-flucytosine suppression. Case 2: A 61-year-old male, diabetic, with uncontrolled sugars, had severe COVID-19 in September 2020 needing oxygen, remdesivir, and steroids; 1 month later, presented with right-sided flank pain and four episodes of painless passage of fleshy tissue per urethra in the last 1 year (Fig. 2). He had multiple episodes of bacterial UTIs which were treated, with complete resolution. The fleshy mass showed septate fungal elements and culture grew Aspergillus flavus sensitive to voriconazole, itraconazole, and posaconazole. He received multiple prolonged courses of voriconazole and caspofungin prior to presenting to us. CT revealed right-sided pyelonephritis with dilated pelvi-calyceal system. The patient was started on 2 weeks of micafungin followed by a prolonged course of voriconazole and 5-flucytosine with close clinical and therapeutic drug monitoring. Case 3: A 68-year-old female, diabetic, had moderate COVID-19 in April 2021, and was given remdesivir and steroids. She was admitted 1 month later with UTI (Pyelonephritis with early forming renal abscess) with urine culture growing CR Klebsiella p. (OXA-48) and C. glabrata for which she was given ceftazidime-A, vibactam, and voriconazole and underwent bilateral DJ stenting followed by stent removal after 1 month along with switching to micafungin in view of repeated candiduria on treatment. She has developed multiple UTIs in the subsequent months with C. auris being isolated twice and bacterial UTIs, treated with antibiotics and micafungin. Subsequent CT revealed retroperitoneal fibrosis encasing the ureters causing obstruction, a biopsy was inconclusive but was empirically started on methotrexate for IgG4 disease. Discussion The proposed immune alteration mechanism of COVID-19 of decreased phagocytic function, uncontrolled sugars, and steroid-related neutrophil dysfunction predispo","PeriodicalId":18325,"journal":{"name":"Medical mycology journal","volume":"60 1","pages":""},"PeriodicalIF":1.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80578013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P440 General protocol applied to the identification and production of new biomarkers with potential use for the diagnosis of histoplasmosis","authors":"Juan David Puerta Arias, J. P. Isaza, E. Moreno, I. Berrio, Luz Elena Cano Restrepo, Tonny W. Naranjo","doi":"10.1093/mmy/myac072.P440","DOIUrl":"https://doi.org/10.1093/mmy/myac072.P440","url":null,"abstract":"Abstract Poster session 3, September 23, 2022, 12:30 PM - 1:30 PM Objective To identify and produce novel biomarkers with potential use for the specific diagnosis of H. capsulatum infection. Methods Here, we design a novel strategy to search and select new Candidate genes for biomarkers that integrates the use of a computational analysis model that includes the application of bioinformatic tools such as OrthoMCL, BLASTp, TargetP, and SignalP, applied on a local collection of proteome database obtained manually from GenBank-NCBI, and the analysis of previously published biological and experimental data sets, including a secreted proteome database obtained from pathogenic yeast-phase H. capsulatum culture filtrates, a Histoplasma yeast and mycelial transcriptomes database, and a urine-peptides database from Histoplasma-immunoassay-positive patients. For the synthesis of the Candidates, an internal protocol for the production of recombinant proteins in prokaryotic and eukaryotic systems was applied. Obtaining polyclonal antibodies (PAb) specific for each biomarker was carried out by adapting a rapid immunization protocol for BALB/c mice. Finally, the computational model was experimentally validated, evaluating the reactivity and specificity of PAb anti-Histoplasma with fungus culture extracts and samples from patients with histoplasmosis. Results Using the computational analysis model, 2 Candidate genes for diagnostic biomarkers were identified. Subsequently, the construction of expression vector for each Candidate and the production of these genes were achieved using a standardized protocol for the production of recombinant proteins. Polyclonal antibodies (PAb) anti-histoplasma were obtained and shown to be reactive against purified H. capsulatum-antigens. Finally, we confirmed the presence of these antigens in yeast culture extracts of H. capsulatum and demonstrated the immunoreactivity of anti-Histoplasma PAb with urine samples from patients previously diagnosed with histoplasmosis. Conclusion The generation of novel strategies that combine data analysis, computational tools, and transcriptomic and proteomic techniques could be very useful for the identification of new biomarker genes and the development of microbiological diagnostic tests for important pathogens.","PeriodicalId":18325,"journal":{"name":"Medical mycology journal","volume":"50 1","pages":""},"PeriodicalIF":1.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83546983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"S8.5c MLST genotyping and phylogenetics of AD-hybrids","authors":"M. Cogliati, Min Chen, Jianping Xu, Megan Hitchcock, J. Chung, Dong-Hoon Yang, V. Rickerts, Marie Desnos Ollivier, João Inácio Silva, W. Meyer, M. Florek, U. Nawrot, Patricia Escandón, A. Puime, F. Roger, S. Bertout","doi":"10.1093/mmy/myac072.S8.5c","DOIUrl":"https://doi.org/10.1093/mmy/myac072.S8.5c","url":null,"abstract":"Abstract S8.5 Genotyping of Cryptococcus neoformans and C. gattii, September 23, 2022, 3:00 PM - 4:30 PM Objectives In a previous study a set of new molecular-type specific primers were designed to apply the standard ISHAM consensus multi-locus sequence typing (MLST) scheme to Cryptococcus neoformans AD hybrids. In the present study, we report the preliminary results of the investigation by MLST of a large number of AD hybrids with the aim to identify the circulating genotypes, their phylogenesis, and population genetics. Methods A total of 50 AD-hybrid isolates from different parts of the world and from different sources were genotyped by MLST. Minimum spanning trees using GoeBurst algorithm were generated by comparing hybrid genotypes and by comparing separately either allele-A and allele-D portions of the hybrid genotypes to the haplotypes recorded in the MLST global database. Results Analysis identified 32 hybrid genotypes grouped in three distinct main clusters (CC12, CC21, and CC30) including 12 isolates each. Both CC12 and CC21 clusters included isolates from different countries and continents but the former grouped only isolates with mating type aADalpha whereas the latter those with mating type alphaADa. Cluster CC30 included only isolates from Ivory Coasts. Heterozygous allelic combinations in each of the seven MLST loci presented two or three combinations more frequent than the other ones. In some isolates, one or more alleles were not amplified after multiple attempts, and therefore, they were considered as lacking. A total of 22 MLST profiles were identified by analyzing separately the allele-A combinations of the hybrids. Comparison with all MLST profiles of VNI, VNII, and VNB included in the MLST global database showed that the allele-A portion of the hybrid genotypes was grouped in few VNI or VNB clusters. In none of the investigated hybrids, the allele-A portion originated from VNII genotypes. Similarly, when the MLST profile of allele-D portion of hybrids was compared to all VNIV genotypes present in the global MLST database, few clusters were identified but, in this case, mostly originated from genotypes not yet found among VNIV haplotypes. Conclusions These preliminary results suggest that the AD hybrids here investigated originated from the mating of A haploids very common in both clinical and environmental isolates and D haploids that are not circulating at present or are very rare. Therefore, it is likely that hybrids originated in the environment where VNIV genotypic diversity is higher and suitable AD combinations can occur. Sequencing of further AD hybrids is in progress to confirm these results.","PeriodicalId":18325,"journal":{"name":"Medical mycology journal","volume":"1 1","pages":""},"PeriodicalIF":1.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89960903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"S3.4d The role of NLRP3 inflammasome in host defense during Talaromyces marneffei infection","authors":"Lu Sha, Wu Jinquan, Xing Liyan, Xiaoxia Zhou","doi":"10.1093/mmy/myac072.S3.4d","DOIUrl":"https://doi.org/10.1093/mmy/myac072.S3.4d","url":null,"abstract":"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.","PeriodicalId":18325,"journal":{"name":"Medical mycology journal","volume":"49 1","pages":""},"PeriodicalIF":1.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90105875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P172 First report of Aspergillus tamarii producing influenza associated invasive pulmonary Aspergillosis","authors":"M. Sahu, Sourabh Chakraborty, Geethu Joe, Rahul Doshi, R. Soman","doi":"10.1093/mmy/myac072.P172","DOIUrl":"https://doi.org/10.1093/mmy/myac072.P172","url":null,"abstract":"Abstract Poster session 2, September 22, 2022, 12:30 PM - 1:30 PM Objective Multiple infections can occur after 2009, pandemic influenza, including fungal and bacterial infections, but data from India are limited. To our knowledge, this is the first reported case of influenza-associated invasive pulmonary aspergillosis (IAPA), caused by Aspergillus tamarii, after infection with pandemic (H1N1) 2009 which was preceded by COVID-19, 20 months before. Methods and Results A 33-year-old male, known asthmatic, had been hospitalized elsewhere in August 2020 with COVID-19 pneumonia for 50 days and had been on mechanical ventilation for 37 days. He had no residual respiratory symptoms 3 months after recovery from COVID-19. He was admitted to Jupiter Hospital in April 2022 with fever, cough, and dyspnea for 8 days, which developed after a cold bath in a temple. HRCT (chest) showed ground glass opacities (GGOs), crazy paving, nodules, and traction bronchiectasis. Review of previous HRCT showed that only GGOs were present (Fig. 1). At admission, the nasopharyngeal swab was positive for pandemic (H1N1) 2009 in the filmarray respiratory panel and no other pathogen was detected. He was treated with oseltamivir. Expectorated sputum examination showed a heavy load of thin septate hyphae, with acute angle branching, resembling Aspergilllus species (Fig. 2). Serum galactomannan was positive (1.8). Based on these features he was diagnosed as a case of probable IAPA and initiated posaconazole (PCZ) treatment. Sputum fungal culture was positive and was identified by MALDI TOF MS as A. tamarii. A. tamarii has been rarely encountered as a human pathogen. Case reports of its involvement in eyelid infection, keratitis, invasive sinonasal infection, and onychomycosis exist. Sensititre MICs were 0.0625 mcg/ml, 0.125 mcg/ml, 0.0625 mcg/ml, and 0.125 mcg/mL for itraconazole, voriconazole, PCZ, and for isavuconazole (ISVCZ) respectively. The usually obtained PCZ trough level with standard dose is 1.2 mg/l which generates AUC of 200R. The usually obtained ISVC) trough level with standard dose is 3 mg/l which generates AUC of 100R. The PKPD index, AUC/MIC of 100, is needed with both these azoles for a therapeutic effectR. Therefore, it would be possible to treat this infection with any of these azoles. PCZ was continued in view of the easy availability of therapeutic drug monitoring (TDM) to assure adequate drug exposure, lower cost, and clinical improvement which had already occurred. Conclusion An infection due to a rare Aspergillus species needs correct identification, MIC determination, and PKPD consideration for appropriate drug selection and management.","PeriodicalId":18325,"journal":{"name":"Medical mycology journal","volume":"1 1","pages":""},"PeriodicalIF":1.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90205506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P102 Nuclear magnetic resonance -based identification of metabolites in dermatophytes","authors":"Anupam Das, Bikash Baishya, Suresh Chandra Ahirwar, Vikramjeet Singh, M. Sen, V. Mittal, J. Agarwal","doi":"10.1093/mmy/myac072.P102","DOIUrl":"https://doi.org/10.1093/mmy/myac072.P102","url":null,"abstract":"Abstract Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM Objectives Nuclear magnetic resonance (NMR) spectroscopy provides a holistic snapshot of the metabolome of an organism. There is a dearth of studies till date that had exploited NMR metabolomic platform to study dermatophytes, despite its potential for rapid identification and subsequent application of the knowledge in performing faster antifungal susceptibility of dermatophytes. Here we attempted to study the frequency of various species of dermatophytes in clinically suspected cases of dermatophytosis and perform NMR-based identification of metabolites in the culture suspensions/cell extracts of T. mentagrophyte and T. rubrum. Methods This was a hospital-based prospective study conducted in the isolates obtained from clinically suspected cases of Dermatophytosis in the patients. Skin, nails, and hair samples of patients suspected with superficial fungal infections were processed for dermatophytes using conventional microbiological methods. NMR-based identification of metabolites was carried out in cell extracts prepared from the culture suspensions of T. mentagrophytes and T. rubrum obtained during the study from a subset of the clinical isolates from the samples. Results Dermatophytes were isolated in 85.88% (219/255) cases, with T. mentagrophyte being isolated in 65% (143/219) of isolates, followed by T. rubrum in 31.5% (69/219) isolates. In NMR study was done in the standard ATCC strains (T. mentagrophyte ATCC9533 and T. rubrum ATCC28188) and representative clinical isolates of both the species. Overall, 24 metabolites were identified in T. rubrum and 23 metabolites in T. mentagrophyte amongst which 22 metabolites were common to both fungus, however, ‘4-hydroxyproline’ and ‘acetate’ was found specific to T. rubrum, and ‘allantoin’ was found specific to T. mentagrophyte. Conclusion T. mentagrophyte was the predmominant dermatophyte species in the study. Amongst the number of metabolites detected in T. rubrum and T. mentagrophyte, ‘4-hydroxyproline’ and ‘acetate’ was found specific to T. rubrum, and ‘allantoin’ was found specific to T. mentagrophyte. These specific metabolites could be useful for as early identification of these dermatophytes as well early determination of antifungal susceptibility by using metabolic endpoints, further large-scale study will be helpful in this regard.","PeriodicalId":18325,"journal":{"name":"Medical mycology journal","volume":"24 1","pages":""},"PeriodicalIF":1.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90303673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}