Laya Reddy, George R Thompson Iii, Natascha Tuznik, Tina A Zolfaghari, Joy Vongspanich Dray, Janneca Ames, Daniel Ho, Scott Crabtree, Jeffrey Fine, Machelle D Wilson, Muna Alnimri, Stuart H Cohen, Alan Koff
Coccidioides is an endemic fungus that causes infections ranging from mild respiratory illness to life-threatening disease, and immunocompromised hosts such as solid organ transplant recipients are at higher risk for disseminated infection and mortality. Our center administers fluconazole prophylaxis to kidney transplant recipients residing in geographic areas with higher incidences of coccidioidomycosis. However, because drug-drug interactions occur between triazoles and immunosuppressants used in transplant medicine, we undertook a study to ascertain whether fluconazole prophylaxis was associated with any important safety outcomes in kidney transplant recipients. This retrospective study evaluated patients who had undergone kidney transplantation between 2016 and 2019. Data on patient demographics, transplant-related clinical information, use of fluconazole prophylaxis (200 mg daily for 6-12 months post-transplant), and patient outcomes were obtained. The primary outcome was mean estimated glomerular filtration rate (eGFR) at 12 months, comparing those who received fluconazole prophylaxis to those who did not. Secondary outcomes included mean eGFR at 3 months, 6 months, and 9 months post-transplant, patient survival, biopsy-proven graft rejection, graft loss, or a new requirement for post-transplant dialysis, all within 12 months post-transplant. The mean eGFR at 12 months was similar between both groups, with 66.4 ml/min/1.73 m² in the fluconazole prophylaxis group vs. 64.3 ml/min/1.73 m² in the non-fluconazole prophylaxis group (P = 0.55). Secondary outcomes were similar across both groups. Multivariable linear regression found no significant association between fluconazole use and graft function. Fluconazole prophylaxis for prevention of coccidioidomycosis was not associated with adverse graft outcomes in kidney transplant recipients.
{"title":"Safety of fluconazole in kidney transplant recipients for prevention of coccidioidomycosis.","authors":"Laya Reddy, George R Thompson Iii, Natascha Tuznik, Tina A Zolfaghari, Joy Vongspanich Dray, Janneca Ames, Daniel Ho, Scott Crabtree, Jeffrey Fine, Machelle D Wilson, Muna Alnimri, Stuart H Cohen, Alan Koff","doi":"10.1093/mmy/myae017","DOIUrl":"10.1093/mmy/myae017","url":null,"abstract":"<p><p>Coccidioides is an endemic fungus that causes infections ranging from mild respiratory illness to life-threatening disease, and immunocompromised hosts such as solid organ transplant recipients are at higher risk for disseminated infection and mortality. Our center administers fluconazole prophylaxis to kidney transplant recipients residing in geographic areas with higher incidences of coccidioidomycosis. However, because drug-drug interactions occur between triazoles and immunosuppressants used in transplant medicine, we undertook a study to ascertain whether fluconazole prophylaxis was associated with any important safety outcomes in kidney transplant recipients. This retrospective study evaluated patients who had undergone kidney transplantation between 2016 and 2019. Data on patient demographics, transplant-related clinical information, use of fluconazole prophylaxis (200 mg daily for 6-12 months post-transplant), and patient outcomes were obtained. The primary outcome was mean estimated glomerular filtration rate (eGFR) at 12 months, comparing those who received fluconazole prophylaxis to those who did not. Secondary outcomes included mean eGFR at 3 months, 6 months, and 9 months post-transplant, patient survival, biopsy-proven graft rejection, graft loss, or a new requirement for post-transplant dialysis, all within 12 months post-transplant. The mean eGFR at 12 months was similar between both groups, with 66.4 ml/min/1.73 m² in the fluconazole prophylaxis group vs. 64.3 ml/min/1.73 m² in the non-fluconazole prophylaxis group (P = 0.55). Secondary outcomes were similar across both groups. Multivariable linear regression found no significant association between fluconazole use and graft function. Fluconazole prophylaxis for prevention of coccidioidomycosis was not associated with adverse graft outcomes in kidney transplant recipients.</p>","PeriodicalId":18586,"journal":{"name":"Medical mycology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10941972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139996794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hyphal pellet formation by Aspergillus species in liquid cultures is one of the main obstacles to high-throughput anti-Aspergillus reagent screening. We previously constructed a hyphal dispersion mutant of Aspergillus fumigatus by disrupting the genes encoding the primary cell wall α-1,3-glucan synthase Ags1 and putative galactosaminogalactan synthase Gtb3 (Δags1Δgtb3). Mycelial growth of the mutant in liquid cultures monitored by optical density was reproducible, and the dose-response of hyphal growth to antifungal agents has been quantified by optical density. However, Δags1Δgtb3 still forms hyphal pellets in some rich growth media. Here, we constructed a disruptant lacking all three α-1,3-glucan synthases and galactosaminogalactan synthase (Δags1Δags2Δags3Δgtb3), and confirmed that its hyphae were dispersed in all the media tested. We established an automatic method to monitor hyphal growth of the mutant in a 24-well plate shaken with a real-time plate reader. Dose-dependent growth suppression and unique growth responses to antifungal agents (voriconazole, amphotericin B, and micafungin) were clearly observed. A 96-well plate was also found to be useful for the evaluation of mycelial growth by optical density. Our method is potentially applicable to high-throughput screening for anti-Aspergillus agents.
{"title":"Real-time monitoring of mycelial growth in liquid culture using hyphal dispersion mutant of Aspergillus fumigatus.","authors":"Ken Miyazawa, Takashi Umeyama, Shogo Takatsuka, Yasunori Muraosa, Yasutaka Hoshino, Shigekazu Yano, Keietsu Abe, Yoshitsugu Miyazaki","doi":"10.1093/mmy/myae011","DOIUrl":"10.1093/mmy/myae011","url":null,"abstract":"<p><p>Hyphal pellet formation by Aspergillus species in liquid cultures is one of the main obstacles to high-throughput anti-Aspergillus reagent screening. We previously constructed a hyphal dispersion mutant of Aspergillus fumigatus by disrupting the genes encoding the primary cell wall α-1,3-glucan synthase Ags1 and putative galactosaminogalactan synthase Gtb3 (Δags1Δgtb3). Mycelial growth of the mutant in liquid cultures monitored by optical density was reproducible, and the dose-response of hyphal growth to antifungal agents has been quantified by optical density. However, Δags1Δgtb3 still forms hyphal pellets in some rich growth media. Here, we constructed a disruptant lacking all three α-1,3-glucan synthases and galactosaminogalactan synthase (Δags1Δags2Δags3Δgtb3), and confirmed that its hyphae were dispersed in all the media tested. We established an automatic method to monitor hyphal growth of the mutant in a 24-well plate shaken with a real-time plate reader. Dose-dependent growth suppression and unique growth responses to antifungal agents (voriconazole, amphotericin B, and micafungin) were clearly observed. A 96-well plate was also found to be useful for the evaluation of mycelial growth by optical density. Our method is potentially applicable to high-throughput screening for anti-Aspergillus agents.</p>","PeriodicalId":18586,"journal":{"name":"Medical mycology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140012914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Candida albicans is a dimorphic opportunistic pathogen in immunocompromised individuals. We have previously demonstrated that sodium houttuyfonate (SH), a derivative of medicinal herb Houttuynia cordata Thunb, was effective for antifungal purposes. However, the physical impediment of SH by C. albicans β-glucan may weaken the antifungal activity of SH. In this study, the interactions of SH with cell wall (CW), extracellular matrix (EM), CW β-glucan, and a commercial β-glucan zymosan A (ZY) were inspected by XTT assay and total plate count in a standard reference C. albicans SC5314 as well as two clinical fluconazole-resistant strains Z4935 and Z5172. After treatment with SH, the content and exposure of CW β-glucan, chitin, and mannan were detected, the fungal clearance by phagocytosis of RAW264.7 and THP-1 was examined, and the gene expressions and levels of cytokines TNF-ɑ and IL-10 were also monitored. The results showed that SH could be physically impeded by β-glucan in CW, EM, and ZY. This impediment subsequently triggered the exposure of CW β-glucan and chitin with mannan masked in a time-dependent manner. SH-induced β-glucan exposure could significantly enhance the phagocytosis and inhibit the growth of C. albicans. Meanwhile, the SH-pretreated fungal cells could greatly stimulate the cytokine gene expressions and levels of TNF-ɑ and IL-10 in the macrophages. In sum, the strategy that the instant physical impediment of C. albicans CW to SH, which can induce the exposure of CW β-glucan may be universal for C. albicans in response to physical deterrent by antifungal drugs.
白色念珠菌是免疫力低下人群中的一种二形机会性病原体。我们曾证实,药用植物 Houttuynia cordata Thunb 的衍生物 Sodium houttuyfonate(SH)对抗真菌有效。然而,白僵菌β-葡聚糖对 SH 的物理阻碍作用可能会削弱 SH 的抗真菌活性。本研究通过 XTT 检测法和平板总数检测了 SH 与细胞壁(CW)、细胞外基质(EM)、CW β-葡聚糖和商用 β-葡聚糖酶联免疫吸附素 A(ZY)之间的相互作用。用 SH 处理后,检测了 CW β-葡聚糖、几丁质和甘露聚糖的含量和暴露量,考察了 RAW264.7 和 THP-1 通过吞噬作用清除真菌的情况,并监测了细胞因子 TNF-ɑ 和 IL-10 的基因表达和水平。结果表明,在 CW、EM 和 ZY 中,β-葡聚糖可对 SH 产生物理阻碍作用。这种阻碍随后以时间依赖的方式引发了 CW β-葡聚糖和甲壳素的暴露,而甘露聚糖则被掩盖。SH 诱导的 β-葡聚糖暴露可显著增强白僵菌的吞噬能力并抑制其生长。同时,经 SH 漂洗的真菌细胞能极大地刺激巨噬细胞中细胞因子基因的表达,提高 TNF-ɑ 和 IL-10 的水平。总之,白僵菌CW对SH的瞬间物理阻碍可诱导CWβ-葡聚糖的暴露,这一策略可能是白僵菌对抗真菌药物物理阻遏的普遍反应。
{"title":"Physical impediment to sodium houttuyfonate conversely reinforces β-glucan exposure stimulated innate immune response to Candida albicans.","authors":"Qirui Wang, Zixu Wang, Chen Xu, Daqiang Wu, Tianming Wang, Changzhong Wang, Jing Shao","doi":"10.1093/mmy/myae014","DOIUrl":"10.1093/mmy/myae014","url":null,"abstract":"<p><p>Candida albicans is a dimorphic opportunistic pathogen in immunocompromised individuals. We have previously demonstrated that sodium houttuyfonate (SH), a derivative of medicinal herb Houttuynia cordata Thunb, was effective for antifungal purposes. However, the physical impediment of SH by C. albicans β-glucan may weaken the antifungal activity of SH. In this study, the interactions of SH with cell wall (CW), extracellular matrix (EM), CW β-glucan, and a commercial β-glucan zymosan A (ZY) were inspected by XTT assay and total plate count in a standard reference C. albicans SC5314 as well as two clinical fluconazole-resistant strains Z4935 and Z5172. After treatment with SH, the content and exposure of CW β-glucan, chitin, and mannan were detected, the fungal clearance by phagocytosis of RAW264.7 and THP-1 was examined, and the gene expressions and levels of cytokines TNF-ɑ and IL-10 were also monitored. The results showed that SH could be physically impeded by β-glucan in CW, EM, and ZY. This impediment subsequently triggered the exposure of CW β-glucan and chitin with mannan masked in a time-dependent manner. SH-induced β-glucan exposure could significantly enhance the phagocytosis and inhibit the growth of C. albicans. Meanwhile, the SH-pretreated fungal cells could greatly stimulate the cytokine gene expressions and levels of TNF-ɑ and IL-10 in the macrophages. In sum, the strategy that the instant physical impediment of C. albicans CW to SH, which can induce the exposure of CW β-glucan may be universal for C. albicans in response to physical deterrent by antifungal drugs.</p>","PeriodicalId":18586,"journal":{"name":"Medical mycology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139931943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xavier Brousse, Sébastien Imbert, Nahéma Issa, Edouard Forcade, Maxime Faure, Jeremy Chambord, Hanta Ramaroson, Hannah Kaminski, Pierre-Yves Dumas, Elodie Blanchard
To estimate the diagnostic performance of Mucorales polymerase chain reaction (PCR) in Bronchoalveolar lavage fluid (BALF) in routine practice. This was a single-center retrospective study including all consecutive patients >18 years who underwent Mucorales PCR assay in BALF between January 2021 and May 2022. Index testing was prospectively performed using the MycoGENIE Aspergillus spp.-Mucorales spp. PCR. The reference was the diagnosis of pulmonary mucormycosis by the Adjudication Committee. Mucorales PCR in BALF was performed for 938 patients and was positive for 21 of 938 (2.2%). Eleven pulmonary mucormycosis (including one disseminated) were diagnosed. Among them, one (9.1%) was classified as proven mucormycosis, three (27.3%) as probable, and seven (63.6%) as possible according to the EORTC/MSGERC 2019 criteria. The main host factor was hematological malignancy (10 of 11, 90.9%). Mucorales PCR was positive in serum for eight patients (72.7%). Three patients had positive PCR in BALF, but negative in serum. The mean cycle threshold value was significantly lower in mucormycosis than false-positive cases. Sensitivity was 72.7% (95% confidence interval [CI], 43.4-90.3%), and specificity was 98.6% (95% CI, 97.6-99.2%). The positive and negative predictive values were 38.1% (95% CI, 20.8-59.1%) and 99.7% (95% CI, 99.1-99.9%), respectively. Mucorales PCR in BALF showed good diagnostic performance for mucormycosis, particularly in combination with serum PCR. A positive result should be interpreted with caution, given the possibility of carriage in the airway. However, its high negative predictive value and specificity suggest the utility of Mucorales PCR in BALF in the diagnosis of pulmonary mucormycosis.
{"title":"Performance of Mucorales spp. qPCR in bronchoalveolar lavage fluid for the diagnosis of pulmonary mucormycosis.","authors":"Xavier Brousse, Sébastien Imbert, Nahéma Issa, Edouard Forcade, Maxime Faure, Jeremy Chambord, Hanta Ramaroson, Hannah Kaminski, Pierre-Yves Dumas, Elodie Blanchard","doi":"10.1093/mmy/myae006","DOIUrl":"10.1093/mmy/myae006","url":null,"abstract":"<p><p>To estimate the diagnostic performance of Mucorales polymerase chain reaction (PCR) in Bronchoalveolar lavage fluid (BALF) in routine practice. This was a single-center retrospective study including all consecutive patients >18 years who underwent Mucorales PCR assay in BALF between January 2021 and May 2022. Index testing was prospectively performed using the MycoGENIE Aspergillus spp.-Mucorales spp. PCR. The reference was the diagnosis of pulmonary mucormycosis by the Adjudication Committee. Mucorales PCR in BALF was performed for 938 patients and was positive for 21 of 938 (2.2%). Eleven pulmonary mucormycosis (including one disseminated) were diagnosed. Among them, one (9.1%) was classified as proven mucormycosis, three (27.3%) as probable, and seven (63.6%) as possible according to the EORTC/MSGERC 2019 criteria. The main host factor was hematological malignancy (10 of 11, 90.9%). Mucorales PCR was positive in serum for eight patients (72.7%). Three patients had positive PCR in BALF, but negative in serum. The mean cycle threshold value was significantly lower in mucormycosis than false-positive cases. Sensitivity was 72.7% (95% confidence interval [CI], 43.4-90.3%), and specificity was 98.6% (95% CI, 97.6-99.2%). The positive and negative predictive values were 38.1% (95% CI, 20.8-59.1%) and 99.7% (95% CI, 99.1-99.9%), respectively. Mucorales PCR in BALF showed good diagnostic performance for mucormycosis, particularly in combination with serum PCR. A positive result should be interpreted with caution, given the possibility of carriage in the airway. However, its high negative predictive value and specificity suggest the utility of Mucorales PCR in BALF in the diagnosis of pulmonary mucormycosis.</p>","PeriodicalId":18586,"journal":{"name":"Medical mycology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139642441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chromoblastomycosis (CBM), a chronic, granulomatous, suppurative mycosis of the skin and subcutaneous tissue, is caused by several dematiaceous fungi. The formation of granulomas, tissue proliferation, and fibrosis in response to these pathogenic fungi is believed to be intricately linked to host immunity. To understand this complex interaction, we conducted a comprehensive analysis of immune cell infiltrates, neutrophil extracellular traps (NETs) formation, and the fibrosis mechanism in 20 CBM lesion biopsies using immunohistochemical and immunofluorescence staining methods. The results revealed a significant infiltration of mixed inflammatory cells in CBM granulomas, prominently featuring a substantial presence of Th2 cells and M2 macrophages. These cells appeared to contribute to the production of collagen I and III in the late fibrosis mechanism, as well as NETs formation. The abundance of Th2 cytokines may act as a factor promoting the bias of macrophage differentiation toward M2, which hinders efficient fungal clearance while accelerates the proliferation of fibrous tissue. Furthermore, the expression of IL-17 was noted to recruit neutrophils, facilitating subsequent NETs formation within CBM granulomas to impede the spread of sclerotic cells. Understanding of these immune mechanisms holds promise for identifying therapeutic targets for managing chronic granulomatous CBM.
着色真菌病(CBM)是一种慢性、肉芽肿性、皮肤和皮下组织化脓性真菌病,由几种脱霉真菌引起。肉芽肿的形成、组织增生和纤维化与这些致病真菌的反应被认为与宿主免疫密切相关。为了了解这种复杂的相互作用,我们采用免疫组化和免疫荧光染色方法,对 20 例 CBM 病变活检组织中的免疫细胞浸润、中性粒细胞胞外陷阱(NET)形成和纤维化机制进行了全面分析。结果显示,CBM 肉芽肿中存在大量混合炎症细胞浸润,主要特征是大量存在 Th2 细胞和 M2 巨噬细胞。这些细胞似乎有助于后期纤维化机制中胶原蛋白 I 和 III 的生成以及 NET 的形成。Th2细胞因子的大量存在可能是促进巨噬细胞向M2分化的一个因素,它阻碍了真菌的有效清除,同时加速了纤维组织的增殖。此外,研究还发现,IL-17 的表达可招募中性粒细胞,促进随后 CBM 肉芽肿内 NET 的形成,从而阻碍硬化细胞的扩散。了解了这些免疫机制,就有望找到治疗慢性肉芽肿性 CBM 的靶点。
{"title":"Neutrophil extracellular traps (NETs) and Th-2 dominant immune responses in chronic granulomatous chromobalstomycosis.","authors":"Huan Huang, Minying Li, Mingfen Luo, Jinjin Zheng, Qian Li, Xiaoyue Wang, Yinghui Liu, Dongmei Li, Liyan Xi, Hongfang Liu","doi":"10.1093/mmy/myae008","DOIUrl":"10.1093/mmy/myae008","url":null,"abstract":"<p><p>Chromoblastomycosis (CBM), a chronic, granulomatous, suppurative mycosis of the skin and subcutaneous tissue, is caused by several dematiaceous fungi. The formation of granulomas, tissue proliferation, and fibrosis in response to these pathogenic fungi is believed to be intricately linked to host immunity. To understand this complex interaction, we conducted a comprehensive analysis of immune cell infiltrates, neutrophil extracellular traps (NETs) formation, and the fibrosis mechanism in 20 CBM lesion biopsies using immunohistochemical and immunofluorescence staining methods. The results revealed a significant infiltration of mixed inflammatory cells in CBM granulomas, prominently featuring a substantial presence of Th2 cells and M2 macrophages. These cells appeared to contribute to the production of collagen I and III in the late fibrosis mechanism, as well as NETs formation. The abundance of Th2 cytokines may act as a factor promoting the bias of macrophage differentiation toward M2, which hinders efficient fungal clearance while accelerates the proliferation of fibrous tissue. Furthermore, the expression of IL-17 was noted to recruit neutrophils, facilitating subsequent NETs formation within CBM granulomas to impede the spread of sclerotic cells. Understanding of these immune mechanisms holds promise for identifying therapeutic targets for managing chronic granulomatous CBM.</p>","PeriodicalId":18586,"journal":{"name":"Medical mycology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139692312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ayşe Sultan Karakoyun, Bram Spruijtenburg, Nevzat Unal, Eelco F J Meijer, Mete Sucu, Süleyha Hilmioğlu-Polat, Jacques F Meis, Theun de Groot, Macit Ilkit
Candida krusei also known as Pichia kudriavzevii is a potentially multidrug-resistant yeast because it is intrinsically resistant to fluconazole and develops acquired resistance to echinocandins and polyenes. Here, we aim to provide a better understanding of the epidemiology and transmission modes of C. krusei infections by comparing invasive bloodstream (n = 35) and non-invasive vaginal (n = 20) C. krusei isolates. The genetic relatedness of the isolates was assessed using a newly described short tandem repeat (STR) analysis and their sensitivity to eight antifungal compounds was evaluated by antifungal susceptibility testing using the CLSI microbroth dilution method. All C. krusei isolates revealed unique STR genotypes, indicating the absence of clonal transmission in the study group. Furthermore, no drug-resistant or non-wild-type isolates were identified. Our findings demonstrated high resolution of STR genotyping for the detection and simultaneous genetic analysis of multiple C. krusei strains in clinical samples and excellent in vitro activity of common antifungal agents against invasive strains.
{"title":"Molecular typing and antifungal susceptibility profile of Candida krusei bloodstream isolates from Türkiye.","authors":"Ayşe Sultan Karakoyun, Bram Spruijtenburg, Nevzat Unal, Eelco F J Meijer, Mete Sucu, Süleyha Hilmioğlu-Polat, Jacques F Meis, Theun de Groot, Macit Ilkit","doi":"10.1093/mmy/myae005","DOIUrl":"10.1093/mmy/myae005","url":null,"abstract":"<p><p>Candida krusei also known as Pichia kudriavzevii is a potentially multidrug-resistant yeast because it is intrinsically resistant to fluconazole and develops acquired resistance to echinocandins and polyenes. Here, we aim to provide a better understanding of the epidemiology and transmission modes of C. krusei infections by comparing invasive bloodstream (n = 35) and non-invasive vaginal (n = 20) C. krusei isolates. The genetic relatedness of the isolates was assessed using a newly described short tandem repeat (STR) analysis and their sensitivity to eight antifungal compounds was evaluated by antifungal susceptibility testing using the CLSI microbroth dilution method. All C. krusei isolates revealed unique STR genotypes, indicating the absence of clonal transmission in the study group. Furthermore, no drug-resistant or non-wild-type isolates were identified. Our findings demonstrated high resolution of STR genotyping for the detection and simultaneous genetic analysis of multiple C. krusei strains in clinical samples and excellent in vitro activity of common antifungal agents against invasive strains.</p>","PeriodicalId":18586,"journal":{"name":"Medical mycology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139642440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Milbemycin oximes are macrocyclic lactones that have a broad spectrum of activity against nematode infection in animals. They are known to block drug efflux, which increases the susceptibility of fungi to azoles. We investigated the effects of milbemycin on the azole susceptibility of fungi (Aspergillus fumigatus, Candida albicans, C. auris, Cryptococcus neoformans, and Trichophyton rubrum). To screen for changes in azole susceptibility, fungal growth was tested on a culture medium containing 1 μg/ml milbemycin. The results showed that milbemycin increased the azole susceptibility of azole-resistant strains of C. albicans, C. auris, C. neoformans, and T. rubrum. Thus, milbemycin might be useful against antifungal drug-resistant strains.
{"title":"Is milbemycin a game changer against antifungal drug-resistant mycoses?","authors":"Rui Kano, Tsuyoshi Yamada, Takashi Tamura, Koichi Makimura","doi":"10.1093/mmy/myae003","DOIUrl":"10.1093/mmy/myae003","url":null,"abstract":"<p><p>Milbemycin oximes are macrocyclic lactones that have a broad spectrum of activity against nematode infection in animals. They are known to block drug efflux, which increases the susceptibility of fungi to azoles. We investigated the effects of milbemycin on the azole susceptibility of fungi (Aspergillus fumigatus, Candida albicans, C. auris, Cryptococcus neoformans, and Trichophyton rubrum). To screen for changes in azole susceptibility, fungal growth was tested on a culture medium containing 1 μg/ml milbemycin. The results showed that milbemycin increased the azole susceptibility of azole-resistant strains of C. albicans, C. auris, C. neoformans, and T. rubrum. Thus, milbemycin might be useful against antifungal drug-resistant strains.</p>","PeriodicalId":18586,"journal":{"name":"Medical mycology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139576176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fungal flora in coastal/inland beach sand and recreational water is a neglected field of study, despite its potential impact on human health. A joint International Society for Human and Animal Mycology/European Confederation for Medical Mycology (ISHAM/ECMM) working group was formed in 2019 with the task to set up a vast international initiative aimed at studying the fungal contamination of beaches and bathing waters. Here we review the importance of the topic, and list the main results and achievements from 12 scientific publications. Fungal contamination exists at different levels, and the genera most frequently found were Aspergillus spp., Candida spp., Fusarium spp., and Cryptococcus spp., both in sand and in water. A site-blind median was found to be 89 colony-forming units of fungi per gram of sand in coastal/inland freshwaters. This threshold has been used for the sand quality criterion of the blue flag in Portugal. Additionally, our data were considered pivotal and therefore used for the first inclusion of fungi as a biological taxon of interest in water quality and sand monitoring recommendations of the World Health Organization's new guidelines on recreational water quality (Vol.1-Chap7). The findings of the consortium also suggest how environmental conditions (climate, salinity, soil pH, nitrogen, etc.) influence microbial communities in different regions, and that yeast species like Candida glabrata, Clavispora lusitaniae, and Meyerozyma guilliermondii have been identified as potential fungal indicators of fecal contamination. Climate change and natural disasters may affect fungal populations in different environments, and because this is still a field of study under exploration, we also propose to depict the future challenges of research and unmet needs.
{"title":"Knowledge and regulation on fungal contamination of sand and water: Progress report and perspectives.","authors":"Jean-Pierre Gangneux, Joao Brandao, Ester Segal","doi":"10.1093/mmy/myad137","DOIUrl":"10.1093/mmy/myad137","url":null,"abstract":"<p><p>Fungal flora in coastal/inland beach sand and recreational water is a neglected field of study, despite its potential impact on human health. A joint International Society for Human and Animal Mycology/European Confederation for Medical Mycology (ISHAM/ECMM) working group was formed in 2019 with the task to set up a vast international initiative aimed at studying the fungal contamination of beaches and bathing waters. Here we review the importance of the topic, and list the main results and achievements from 12 scientific publications. Fungal contamination exists at different levels, and the genera most frequently found were Aspergillus spp., Candida spp., Fusarium spp., and Cryptococcus spp., both in sand and in water. A site-blind median was found to be 89 colony-forming units of fungi per gram of sand in coastal/inland freshwaters. This threshold has been used for the sand quality criterion of the blue flag in Portugal. Additionally, our data were considered pivotal and therefore used for the first inclusion of fungi as a biological taxon of interest in water quality and sand monitoring recommendations of the World Health Organization's new guidelines on recreational water quality (Vol.1-Chap7). The findings of the consortium also suggest how environmental conditions (climate, salinity, soil pH, nitrogen, etc.) influence microbial communities in different regions, and that yeast species like Candida glabrata, Clavispora lusitaniae, and Meyerozyma guilliermondii have been identified as potential fungal indicators of fecal contamination. Climate change and natural disasters may affect fungal populations in different environments, and because this is still a field of study under exploration, we also propose to depict the future challenges of research and unmet needs.</p>","PeriodicalId":18586,"journal":{"name":"Medical mycology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139403535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amjad N Kanj, Irene Riestra Guiance, Theodore J Kottom, Kyle J Schaefbauer, Malay Choudhury, Andrew H Limper, Joseph H Skalski
Overgrowth of the fungus Wallemia mellicola in the intestines of mice enhances the severity of asthma. Wallemia mellicola interacts with the immune system through Dectin-2 expressed on the surface of myeloid and intestinal epithelial cells. Using Dectin-2-deficient mice, we show that the interaction of W. mellicola with Dectin-2 is essential for the gut-lung pathways, enhancing the severity of asthma in mice with W. mellicola intestinal dysbiosis. These findings offer better insight into dysbiosis-associated inflammation and highlight the role pattern recognition receptors have in immune recognition of commensal fungi in the gut, leading to alterations in immune function in the lungs.
{"title":"The intestinal commensal fungus Wallemia mellicola enhances asthma in mice through Dectin-2.","authors":"Amjad N Kanj, Irene Riestra Guiance, Theodore J Kottom, Kyle J Schaefbauer, Malay Choudhury, Andrew H Limper, Joseph H Skalski","doi":"10.1093/mmy/myae004","DOIUrl":"10.1093/mmy/myae004","url":null,"abstract":"<p><p>Overgrowth of the fungus Wallemia mellicola in the intestines of mice enhances the severity of asthma. Wallemia mellicola interacts with the immune system through Dectin-2 expressed on the surface of myeloid and intestinal epithelial cells. Using Dectin-2-deficient mice, we show that the interaction of W. mellicola with Dectin-2 is essential for the gut-lung pathways, enhancing the severity of asthma in mice with W. mellicola intestinal dysbiosis. These findings offer better insight into dysbiosis-associated inflammation and highlight the role pattern recognition receptors have in immune recognition of commensal fungi in the gut, leading to alterations in immune function in the lungs.</p>","PeriodicalId":18586,"journal":{"name":"Medical mycology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10898867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139707161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ding Li, Lin Wang, Zhihong Zhao, Changsen Bai, Xichuan Li
Followed by Candida albicans, Candida glabrata ranks as the second major species contributing to invasive candidiasis. Given the higher medical burden and lower susceptibility to azoles in C. glabrata infections, identifying these infections is critical. From 2016 to 2021, patients with deep-seated candidiasis due to C. glabrata and non-glabrata Candida met the criteria to be enrolled in the study. Clinical data were randomly divided into training and validation cohorts. A predictive model and nomogram were constructed using R software based on the stepwise algorithm and logistic regression. The performance of the model was assessed by the area under the receiver operating characteristic curve and decision curve analysis (DCA). A total of 197 patients were included in the study, 134 of them infected with non-glabrata Candida and 63 with C. glabrata. The predictive model for C. glabrata infection consisted of gastrointestinal cancer, co-infected with bacteria, diabetes mellitus, and kidney dysfunction. The specificity was 84.1% and the sensitivity was 61.5% in the validation cohort when the cutoff value was set to the same as the training cohort. Based on the model, treatment for patients with a high-risk threshold was better than 'treatment for all' in DCA, while opting low-risk patients out of treatment was also better than 'treatment for none' in opt-out DCA. The predictive model provides a rapid method for judging the probability of infections due to C. glabrata and will be of benefit to clinicians making decisions about therapy strategies.
{"title":"A novel model for predicting deep-seated candidiasis due to Candida glabrata among cancer patients: A 6-year study in a cancer center of China.","authors":"Ding Li, Lin Wang, Zhihong Zhao, Changsen Bai, Xichuan Li","doi":"10.1093/mmy/myae010","DOIUrl":"10.1093/mmy/myae010","url":null,"abstract":"<p><p>Followed by Candida albicans, Candida glabrata ranks as the second major species contributing to invasive candidiasis. Given the higher medical burden and lower susceptibility to azoles in C. glabrata infections, identifying these infections is critical. From 2016 to 2021, patients with deep-seated candidiasis due to C. glabrata and non-glabrata Candida met the criteria to be enrolled in the study. Clinical data were randomly divided into training and validation cohorts. A predictive model and nomogram were constructed using R software based on the stepwise algorithm and logistic regression. The performance of the model was assessed by the area under the receiver operating characteristic curve and decision curve analysis (DCA). A total of 197 patients were included in the study, 134 of them infected with non-glabrata Candida and 63 with C. glabrata. The predictive model for C. glabrata infection consisted of gastrointestinal cancer, co-infected with bacteria, diabetes mellitus, and kidney dysfunction. The specificity was 84.1% and the sensitivity was 61.5% in the validation cohort when the cutoff value was set to the same as the training cohort. Based on the model, treatment for patients with a high-risk threshold was better than 'treatment for all' in DCA, while opting low-risk patients out of treatment was also better than 'treatment for none' in opt-out DCA. The predictive model provides a rapid method for judging the probability of infections due to C. glabrata and will be of benefit to clinicians making decisions about therapy strategies.</p>","PeriodicalId":18586,"journal":{"name":"Medical mycology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139692311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}