Aspergillus-specific antibodies are diagnostic indicators of allergic bronchopulmonary aspergillosis (ABPA) and chronic pulmonary aspergillosis (CPA). Tests for detecting Aspergillus-specific antibodies were not used clinically in Japan, and the production of the Aspergillus precipitin test was discontinued. Thus, alternative tests for diagnosing aspergillosis are urgently needed. We retrospectively evaluated 64 patients with suspected ABPA and CPA who underwent precipitin antibody testing. Serum Aspergillus IgG levels were measured and compared using the Bordier Aspergillus fumigatus ELISA and the Platelia Aspergillus IgG (Bio-Rad) kits. Of the participants, 18 were diagnosed with CPA, and 8 were diagnosed with ABPA. Both the Bordier and Bio-Rad kits showed high sensitivity and specificity for CPA and ABPA. The area under the receiver operating characteristic curves for the Bordier and Bio-Rad kits were 0.97 and 0.95, respectively, for CPA, and 0.89 and 0.91, respectively, for ABPA. In contrast to the Bordier kit, the Bio-Rad kit showed relatively low anti-Aspergillus IgG levels and lower sensitivity to non-fumigatus Aspergillus infections. The Aspergillus-specific IgG ELISA tests showed sufficient diagnostic accuracy. Therefore, these assays are recommended as alternatives to the precipitin kit for diagnosing aspergillosis in clinical settings in Japan.

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Candida albicans, the most common pathogenic fungus, can form biofilms on the surface of medical devices and often causes bloodstream infections. Biofilms have a complex structure composed of microorganisms and a surrounding extracellular matrix. Biofilms are difficult to treat because they are resistant to antifungal drugs and the host environment. Nearly one in four patients with candidemia have a polymicrobial infection. These polymicrobial biofilms, especially those comprising cross-kingdom species of fungi and bacteria, can lead to long hospital stays and high mortality rates. This review outlines the unique interactions of dual-species biofilms with Candida albicans and the clinically important bacteria Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli.

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Chronic pulmonary aspergillosis (CPA) represents a spectrum of lung disorders caused by local proliferation of Aspergillus hyphae in individuals with non-systemic or mildly systemic immunodepression or altered pulmonary integrity due to underlying disease. While long-term systemic antifungal treatment is still the mainstay for management, surgery is considered mainly in rarer invasive disease manifestations such as sinusitis and osteomyelitis. Optimal application of existing antifungal agents with suitable pharmacokinetic properties is important for the treatment of diseases such as CPA, which requires long-term use. Appropriate management of side effects by therapeutic drug monitoring, maintenance of adherence, and assessment of drug resistance to Aspergillus can provide safe and effective treatment in the future. Most available antifungal agents for the management of mycoses in humans have disadvantages that can limit their use in clinical practice. By contrast, second generation antifungals such as triazoles have advantages of extended antifungal spectrum and availability in both oral and intravenous formulations. Isavuconazole, a new extended spectrum triazole, has been shown to be effective against Aspergillus. The safety profile and excellent pharmacokinetic characteristics of isavuconazole make it an attractive option for treatment of invasive fungal infections including CPA. With this drug now available in Japan, new evidence is expected to expand treatment options. This review focuses on the selection of antifungal agents based on national and international guidelines and the characteristics of each agent for their appropriate use in CPA.

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Candida species are common human pathogens that cause a wide range of diseases ranging from superficial to invasive candidiasis. However, basic studies focusing on the mechanisms underlying these diseases are limited. This article reviews our previous research on the mechanisms of superficial and invasive candidiasis, the virulence of Candida species, and Candida species fitness to hosts. Regarding invasive candidiasis, we focused on two types of infections: ocular candidiasis and endogenous candidiasis from the gastrointestinal tract. Using an established ocular candidiasis mouse model, along with retrospective epidemiological research, we found a strong association between Candida albicans and ocular candidiasis. Regarding endogenous candidiasis, research using Candida auris indicated that invasive strains had a higher capability for gastrointestinal tract colonization and showed greater dissemination compared with non-invasive strains. In terms of superficial candidiasis, we focused on the defense mechanism in vulvovaginal candidiasis. The results suggested that stimulated invariant natural killer T cells played a protective role against C. albicans vaginal infection and might be a therapeutic target for vulvovaginal candidiasis. Concerning Candida species fitness, we focused on environmental factors, particularly oxygen concentration, and evaluated biofilm formation under various oxygen concentrations, revealing that each Candida species favored different oxygen concentrations. In particular, Candida tropicalis showed greater biofilm formation under hypoxic conditions. Our research revealed several insights for understanding the exact mechanisms of candidiasis, which might lead to better control of Candida species infections and appropriate treatment.

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The hyphal surface of cells of filamentous fungi is covered with cell wall, which is mainly composed of polysaccharides. Since the cell wall is the first structure to come in contact with the infection host, the environment, and the fungus itself, the elucidation of the cell wall structure and biogenesis is essential for understanding fungal ecology. Among filamentous fungi, the genus Aspergillus is an important group in the industrial, food, and medical fields. It is known that Aspergillus species form hyphal pellets in shake liquid culture. The authors previously found the role of α-1,3-glucan in hyphal aggregation in Aspergillus species. In addition, extracellular polysaccharide galactosaminogalactan contributed to hyphal aggregation as well, and dual disruption of biosynthesis genes of α-1,3-glucan and galactosaminogalactan resulted in complete hyphal dispersion in shake liquid culture. The characteristic of mycelia to form pellets under liquid culture conditions was the main reason why the growth measurement methods used for unicellular organisms could not be applied. We reported that hyphal growth of the dual disruption mutant could be measured by optical density. A real-time plate reader could be used to determine the growth curve of the mycelial growth of the dual disruption mutant. This measurement approach not only provides basic microbiological insights in filamentous fungi, but also has the potential to be applied to high-throughput screening of anti-Aspergillus drugs.

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