Article
Multidisciplinary Sciences
Yaojun Tong, Jingyu Zhang, Nuo Sun, Xiang-Ming Wang, Qi Wei, Yu Zhang, Ren Huang, Yingying Pu, Huanqin Dai, Biao Ren, Gang Pei, Fuhang Song, Guoliang Zhu, Xinye Wang, Xuekui Xia, Xiangyin Chen, Lan Jiang, Shenlin Wang, Liming Ouyang, Ning Xie, Buchang Zhang, Yuanying Jiang, Xueting Liu, Richard Calderone, Fan Bai, Lixin Zhang, Gil Alterovitz
Summary: This study reveals a novel approach of reversing multidrug resistance in Candida albicans by using berberine to exploit the overexpressed drug efflux pump Mdr1p for its own transport, leading to compromised mitochondrial function and selective elimination of multidrug-resistant cells. Berberine treatment prolonged the survival time of mice with Mdr1p overexpressed candidiasis, suggesting a potential direction for anti-MDR drug discovery.
Article
Microbiology
Masakazu Niimi, Kyoko Niimi, Koichi Tanabe, Richard D. Cannon, Erwin Lamping
Summary: Overexpression of ATP-binding cassette (ABC) transporters is the main cause of drug resistance in fungal pathogens. Milbemycins, enniatin B, beauvericin, and FK506 are potential broad-spectrum fungal multidrug efflux pump inhibitors. Investigating naturally generated inhibitor-resistant mutants can provide insights into the structure-activity relationships in ABC transporters.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Immunology
Jie Tu, Tianbao Zhu, Qingwen Wang, Wanzhen Yang, Yahui Huang, Defeng Xu, Na Liu, Chunquan Sheng
Summary: Candida auris is a serious public health threat that has caused a global epidemic due to its multi-drug resistance, remarkable transmissibility, and high mortality. A novel benzoanilide antifungal agent, compound A1, was discovered through a comprehensive strategy involving phenotypic screening, hit optimization, antifungal assays, and mechanism exploration. Compound A1 showed potent efficacy against Candida auris infection both in vitro and in vivo. Mechanistic investigation revealed that compound A1 inhibited the biosynthesis of virulence factors and fungal cell walls by blocking glycosylphosphatidylinositol (GPI) and GPI-anchored proteins. Therefore, compound A1 represents a promising lead compound for combating drug-resistant candidiasis.
EMERGING MICROBES & INFECTIONS
(2023)
Article
Immunology
Collins K. Boahen, Roy Oelen, Kieu Le, Mihai G. Netea, Lude Franke, Monique G. P. van der Wijst, Vinod Kumar
Summary: Both gene expression and protein concentrations are regulated by genetic variants. Exploring the regulation of eQTLs and pQTLs simultaneously in a context- and cell-type dependent manner may help unravel the mechanistic basis for genetic regulation of pQTLs. By conducting meta-analysis of Candida albicans-induced pQTLs from two population-based cohorts and intersecting the results with Candida-induced cell-type specific expression association data (eQTL), we found systematic differences between pQTLs and eQTLs, indicating the limitation of using eQTLs as a proxy for pQTLs. Additionally, our study identified SNPs affecting protein networks and implicated specific genomic loci through colocalization of pQTLs and eQTLs signals.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Chemistry, Medicinal
Martina Raschig, Bernardo Ramirez-Zavala, Johannes Wiest, Marco Saedtler, Marcus Gutmann, Ulrike Holzgrabe, Joachim Morschhauser, Lorenz Meinel
Summary: Increasing resistance to antifungal drugs poses a challenge to anti-infective therapies and contributes to mortality in infections caused by drug-resistant Candida species and strains. This study explores the use of naturally occurring molecules as lead structures for the development of new antifungal agents. The synthesized azobenzene derivatives showed inhibitory effects on both fluconazole-susceptible and fluconazole-resistant Candida species, indicating their potential therapeutic value.
ARCHIV DER PHARMAZIE
(2023)
Article
Microbiology
Yoshihiro Ojima, Naoki Yokota, Yuki Tanibata, Shinsuke Nerome, Masayuki Azuma
Summary: This study investigated the mechanism of toxicity of Toyocamycin (TM) and its analogs to Candida albicans. It was found that the absence of purine nucleoside transport activity from Saccharomyces cerevisiae (S. cerevisiae) made it less susceptible to TM and its analogs. However, when the concentrative nucleoside transporter (CNT) of Candida albicans (C. albicans) was expressed in S. cerevisiae, the sensitivity to TM and its analogs was restored. In addition, introducing human CNT3 into S. cerevisiae also made it sensitive to TM and its analogs. These findings enhance our understanding of the mechanisms of action of adenosine analogs toward Candida pathogens and human cells.
MICROBIOLOGY SPECTRUM
(2022)
Article
Dentistry, Oral Surgery & Medicine
Cesar Augusto Abreu-Pereira, Marlise Inez Klein, Carmelia Isabel Vitorino Lobo, Ana Luiza Gorayb Pereira, Claudia Carolina Jordao, Ana Claudia Pavarina
Summary: This study evaluated the effectiveness of DNase I combined with antimicrobial photodynamic therapy against biofilms formed by a fluconazole-resistant Candida albicans strain. The results showed that DNase treatment combined with aPDT could significantly reduce cell viability and the components of the biofilm.
Article
Microbiology
Valentin Borgeat, Danielle Brandalise, Frederic Grenouillet, Dominique Sanglard
Summary: Candida lusitaniae is an opportunistic pathogen in humans that can rapidly acquire multidrug resistance, with the ABC transporter CDR1 playing an important role in azole resistance.
Article
Biophysics
Baohuan Wu, Sixiang Sai, Keke Li, Xingchen Sun, Jingtian Han, Baocheng Tian
Summary: This study designed maleimide functionalized, voriconazole (VCZ) loaded mixed micelles (Mal-VCZ-MM) for effective hydrophobic ophthalmic drug delivery, leading to significantly higher antifungal effect compared to free VCZ solution and VCZ-loaded micelles.
COLLOIDS AND SURFACES B-BIOINTERFACES
(2022)
Article
Nanoscience & Nanotechnology
Feng Gu, Shan Hu, Yunjian Wu, Changyu Wu, Ying Yang, Bing Gu, Hong Du
Summary: This study successfully detected the drug resistance of non-Candida albicans using SERS technology combined with OPLS-DA analysis. The method is non-destructive to the cell wall and easy to operate, showing promising clinical application potential.
INTERNATIONAL JOURNAL OF NANOMEDICINE
(2022)
Article
Ophthalmology
Ahmad Masoumi, Mohammad Soleimani, Momeneh Azizkhani, Alireza Izadi, Kasra Cheraqpour, Seyed Ali Tabatabaei, Sadegh Khodaveisi, Mehdi Aminzadeh
Summary: This retrospective study analyzed the clinical features, predisposing factors, and management of Candida spp. induced keratitis. The results showed that corneal thinning was found in 63.0% of the eyes, while corneal perforation occurred in 29.6% of the eyes. Corneal thinning and perforation were more common in Candida albicans compared to non-albicans spp. The most common predisposing factors were topical steroid use, previous corneal transplantation, and preexisting ocular surface disease. Glue application and therapeutic penetrating keratoplasty were required for some cases. Local immunosuppression and ocular surface disease play a significant role in Candida keratitis. Candida albicans appears to be more invasive than non-albicans spp.
OCULAR IMMUNOLOGY AND INFLAMMATION
(2023)
Article
Integrative & Complementary Medicine
Zhijun Han, Xiaofen Tan, Juan Sun, Tianming Wang, Guiming Yan, Changzhong Wang, Kelong Ma
Summary: This study established a murine model of UC with C. albicans colonization and comprehensively examined the major bioactive constituents and potential mechanism of SHD against UC with fungal dysbiosis using systems pharmacology and in vivo transcriptomics. The results indicated that SHD could be a candidate for the treatment of fungal dysbiosis-associated UC via TLR4-NF-kappa B and PI3K-Akt signaling pathways.
Article
Microbiology
Sudisht K. K. Sah, Soumyaroop Bhattacharya, Anshuman Yadav, Farha Husain, Aissatou B. K. T. Ndiaye, Michael D. D. Kruppa, Jeffrey J. J. Hayes, Elena Rustchenko
Summary: The researchers identified factors that decrease Candida albicans susceptibility to antifungal drugs and found that certain genes on chromosome 2 play a role in regulating cell wall composition and drug susceptibility.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Microbiology
Teresa R. O'Meara, Matthew J. O'Meara
Summary: The study focused on building a comprehensive and unbiased co-expression network for Candida albicans, known as CalCEN, using data from RNA sequencing runs. This network was successfully used to predict gene function and identified a novel cell cycle regulator, CCJ1. The tool provides a valuable resource for future analyses of gene function in C. albicans.
Article
Pharmacology & Pharmacy
Ting-Lun Yang, Chien-Ming Hsieh, Ling-Jei Meng, Tsuimin Tsai, Chin-Tin Chen
Summary: In this study, oleic acid-based self micro-emulsifying delivery systems (OA-SMEDDS) were developed for delivering clotrimazole (CLT) to enhance its efficacy and reduce toxicity. The results showed that CLT-loaded OA-SMEDDS had a higher drug loading capacity and maintained good storage stability. It also exhibited a significantly lower minimum inhibitory concentration (MIC50) in Candida albicans compared to CLT dissolved in DMSO. Furthermore, CLT-loaded OA-SMEDDS could effectively prevent biofilm formation and destroy the intact biofilm structure of Candida albicans. Evaluation of CLT-loaded OA-SMEDDS gel demonstrated its superior antifungal properties compared to commercially available products in inhibiting wild-type and drug-resistant species of Candida.
Article
Microbiology
Muneyoshi Kimura, Yuki Asano-Mori, Takashi Sakoh, Masahiro Abe, Keigo Ueno, Yasutaka Hoshino, Shigeki Nakamura, Takashi Umeyama, Satoshi Yamagoe, Yoshitsugu Miyazaki, Masaru Baba, Chikako Okada, Sho Ogura, Takashi Mitsuki, Kyosuke Yamaguchi, Mitsuhiro Yuasa, Daisuke Kaji, Kosei Kageyama, Aya Nishida, Yuki Taya, Kazuya Ishiwata, Shinsuke Takagi, Hisashi Yamamoto, Go Yamamoto, Naoyuki Uchida, Atsushi Wake, Shuichi Taniguchi, Hideki Araoka
Summary: Limited data are available on breakthrough fungemia in patients with hematological disorders. This study reviewed cases of breakthrough fungemia among adult patients with hematological diseases between 2008 and 2019. The results demonstrate the clinical characteristics and mortality factors associated with breakthrough fungemia in this patient population.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Microbiology
Hazim O. Khalifa, Vit Hubka, Akira Watanabe, Minoru Nagi, Yoshitsugu Miyazaki, Takashi Yaguchi, Katsuhiko Kamei
Summary: This study evaluated the prevalence of antifungal resistance, genetic mechanisms associated with resistance, and genotyping of Candida krusei. The results showed that most isolates were susceptible to most drugs, but a small portion showed resistance. Overexpression of ABC1 gene and FKS1 HS1 mutations were the main mechanisms of resistance. Genotyping confirmed the existence of two main subpopulations.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Microbiology
Ryosuke Yamamuro, Muneyoshi Kimura, Yuki Asano-Mori, Masahiro Abe, Shigeki Nakamura, Takashi Umeyama, Satoshi Yamagoe, Yoshitsugu Miyazaki, Sho Ogura, Takashi Sakoh, Takashi Mitsuki, Kyosuke Yamaguchi, Mitsuhiro Yuasa, Daisuke Kaji, Kosei Kageyama, Aya Nishida, Yuki Taya, Kazuya Ishiwata, Shinsuke Takagi, Hisashi Yamamoto, Go Yamamoto, Naoyuki Uchida, Atsushi Wake, Shuichi Taniguchi, Hideki Araoka
Summary: There are limited studies on the clinical course of rare/cryptic species-induced invasive aspergillosis (IA) in allo-HSCT recipients. In this retrospective study, it was found that more than half of the proven IA cases were caused by rare/cryptic species. Surgical treatment could be an important option for the management of IA caused by these rare/cryptic species.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Microbiology
Masakazu Niimi, Kyoko Niimi, Koichi Tanabe, Richard D. Cannon, Erwin Lamping
Summary: Overexpression of ATP-binding cassette (ABC) transporters is the main cause of drug resistance in fungal pathogens. Milbemycins, enniatin B, beauvericin, and FK506 are potential broad-spectrum fungal multidrug efflux pump inhibitors. Investigating naturally generated inhibitor-resistant mutants can provide insights into the structure-activity relationships in ABC transporters.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Infectious Diseases
Takuro Koshikawa, Masahiro Abe, Minoru Nagi, Yoshitsugu Miyazaki, Hiromu Takemura
Summary: This study investigates the biofilm-forming capabilities of Candida species under different oxygen conditions. The results show that C. albicans favors aerobic conditions to form biofilms, while C. tropicalis demonstrates higher biofilm formation ability and promotes hyphal growth under microaerobic conditions.
JOURNAL OF INFECTION AND CHEMOTHERAPY
(2022)
Article
Microbiology
Marie Yamashita, Mahoko Ikeda, Ito Kato, Yuki Ohama, Mizuo Ando, Masako Ikemura, Daisuke Jubishi, Yoshiaki Kanno, Koh Okamoto, Takashi Umeyama, Shigeki Nakamura, Yoshitsugu Miyazaki, Shu Okugawa, Kyoji Moriya
Summary: Prototheca wickerhamii infection in the pharyngeal mucosa of a 53-year-old immunocompetent female was reported. The initial misdiagnosis as cryptococcosis was corrected after DNA sequencing identified P. wickerhamii. The infection did not worsen during antifungal treatment.
ANNALS OF CLINICAL MICROBIOLOGY AND ANTIMICROBIALS
(2022)
Article
Microbiology
Jasper E. James, Jacinta Santhanam, Latiffah Zakaria, Nuraini Mamat Rusli, Mariahyati Abu Bakar, Satinee Suetrong, Jariya Sakayaroj, Mohd Fuat Abdul Razak, Erwin Lamping, Richard D. Cannon
Summary: Fusarium infections are common in humans and economically important plants, with the Fusarium solani species complex (FSSC) being the most frequent cause in humans. This study analyzed the genotypic and phenotypic characteristics of FSSC isolates from Malaysia and identified eight different species. The taxonomic relationships were resolved phylogenetically, but a more precise MLST scheme is needed for reliable species assignment of FSSC isolates.
Article
Infectious Diseases
Shigeru Kohno, Koichi Izumikawa, Takahiro Takazono, Taiga Miyazaki, Minoru Yoshida, Katsuhiko Kamei, Kenji Ogawa, Shuichi Taniguchi, Koichi Akashi, Kazuhiro Tateda, Hiroshi Mukae, Yoshitsugu Miyazaki, Fumito Okada, Yoshinobu Kanda, Hiroshi Kakeya, Junko Suzuki, Shun-ichi Kimura, Mitsukazu Kishida, Miyuki Matsuda, Yoshihito Niki
Summary: The study showed that isavuconazole demonstrated good efficacy and safety in treating Japanese patients with chronic pulmonary aspergillosis and cryptococcosis, which are currently not indicated for the drug.
JOURNAL OF INFECTION AND CHEMOTHERAPY
(2023)
Article
Microbiology
Jasper E. James, Jacinta Santhanam, Richard D. Cannon, Erwin Lamping
Summary: In this study, the transcriptional response of F. keratoplasticum to voriconazole exposure was assessed. Upregulated ergosterol biosynthesis gene duplicates were found, indicating the presence of an alternative ergosterol biosynthesis salvage pathway. The study also suggested the induction of additional sterol biosynthesis pathways and the expression of ABC efflux pumps in fusaria. The role of FkSR and FkAtrR in coordinating the response of FSSC species to azole antifungal exposure was also investigated. Genome mining provided a better understanding of antifungal drug resistance mechanisms in fusaria.
Review
Pharmacology & Pharmacy
Yoshio Takesue, Yuki Hanai, Kazutaka Oda, Yukihiro Hamada, Takashi Ueda, Toshihiko Mayumi, Kazuaki Matsumoto, Satoshi Fujii, Yoshiko Takahashi, Yoshitsugu Miyazaki, Toshimi Kimura
Summary: Increased adverse effects of Voriconazole, an antifungal drug, are observed in Asians due to the high rate of poor metabolizers. This therapeutic drug monitoring (TDM) guideline provides recommendations according to ethnic group.
CLINICAL THERAPEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Maryam Alhumaidi, Lea-Marie Nentwig, Hadiar Rahman, Lutz Schmitt, Andrew Rudrow, Andrzej Harris, Cierra Dillon, Lucas Restrepo, Erwin Lamping, Nidhi Arya, Suresh V. Ambudkar, John S. Choy, John Golin
Summary: In this study, the structure-function relationship of the conserved gates and gating regions in ABC multidrug transporters was investigated. The findings reveal that the gating region residues not only play a role in molecular gating but also in allosteric regulation, conformational switching, and protein folding.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Infectious Diseases
Yuto Suga, Noriyuki Watanabe, Kaima Suzuki, Sachie Koyama, Yoshitada Taji, Hiroto Hirano, Takahiro Hayashi, Masahiro Abe, Yoshitsugu Miyazaki, Yasutaka Baba, Hiroki Kurita, Kotaro Mitsutake, Yasuhiro Ebihara
Summary: Herein, we present a case of otitis externa caused by Malassezia slooffiae complicated with mastoiditis. The patient had fever and severe otorrhea, and was diagnosed with otitis media and mastoiditis based on clinical manifestations and imaging findings. The infection was successfully treated with liposomal amphotericin B and voriconazole.
JOURNAL OF INFECTION AND CHEMOTHERAPY
(2023)
Review
Immunology
Keigo Ueno, Soichiro Tsuge, Kiminori Shimizu, Yoshitsugu Miyazaki
Summary: Cryptococcosis is a potentially lethal fungal infection caused by Cryptococcus neoformans and C. gattii species complexes. Currently, there is no commercially available prophylactic vaccine and the protective immunity is still under investigation. Whole-cell vaccines, including modified highly immunostimulating strains, have shown effectiveness in prolonging life and suppressing fungal burden in mice, and cross-reactivity to other fungal pathogens. These findings provide valuable insights for vaccine development. In this review, we discuss the advantages and disadvantages of whole-cell vaccines against cryptococcosis.
MICROBIOLOGY AND IMMUNOLOGY
(2023)
Article
Mycology
Naobumi Tochigi, Sota Sadamoto, Shinji Oura, Yasuko Kurose, Yoshitsugu Miyazaki, Kazutoshi Shibuya
Summary: The study aimed to develop an AI-based histological diagnostic system for automated identification of mucormycosis and aspergillosis. By analyzing the angle of independent hyphae and tortuosity of each hypha, the system successfully distinguished between the two diseases.
MEDICAL MYCOLOGY JOURNAL
(2022)
Article
Mycology
Madoka Tateno, Takashi Umeyama, Tatsuya Inukai, Shogo Takatsuka, Yasutaka Hoshino, Satoshi Yamagoe, Somay Yamagata Murayama, Keiko Ishino, Yoshitsugu Miyazaki
Summary: In this study, the researchers successfully introduced the A. fumigatus cyp51A gene into A. lentulus using the CRISPR/Cas9 system, and found that Cyp51A is involved in the azole resistance of A. lentulus. This finding may contribute to the understanding of the resistance mechanism and the development of new antifungal drugs.
MEDICAL MYCOLOGY JOURNAL
(2022)