Aspergillus species are common hyphal fungi. In addition to allergies and mycotoxicosis, Aspergillus species can cause various infections known as aspergillosis. Aspergillosis of the respiratory tract, central nervous system, skin and soft tissues is well described. However, musculoskeletal infections due to invasive aspergillosis are not well described. Fungal joint infection due to invasive aspergillosis is a rare form of septic arthritis. In this case report, a patient who admitted to our hospital for liver transplantation and developed knee joint arthritis caused by Aspergillus flavus/Aspergillus oryzae during this process was presented. A 28-year-old male patient with autoimmune hepatitis was admitted to hospital with decompensated liver cirrhosis and encephalopathy. The patient, who was awaiting an emergency liver transplant, developed pain, swelling and limitation of movement in his right knee and appropriate consultations and tests were requested. Three joint fluid cultures taken one day apart and nine days later were positive for fungal growth. Macroscopic examination of the mould growth and microscopic examination with lactophenol cotton blue suggested a species belonging to the A.flavus complex and the isolate was identified as A.flavus/A.oryzae by matrix-assisted laser desorption/ionisation mass spectrometry (MALDI-TOF MS) (EXS 2600, Zybio, China). As a result of ITS gene sequencing, the species was determined to be A.oryzae. As cases have been reported where A.flavus and A.oryzae species could not be distinguished by ITS gene sequencing, the pathogen was defined as A.flavus/oryzae. The patient died of liver disease during treatment with amphotericin B. There are few cases of arthritis caused by Aspergillus species in the literature. Aspergillus species found in joint infections are, Aspergillus fumigatus, A.flavus, Aspergillus niger and Aspergillus terreus species complexes, in order of frequency. A.flavus and A.oryzae are closely related. They are difficult to distinguish by conventional methods, MALDI-TOF MS or ITS region sequencing, which is commonly used for genus/species identification in fungi. The number of Aspergillus arthritis cases is low and the identification methods applied to the species reported as causative agents in most studies can identify at the species complex level. In addition, it can be assumed that species not previously reported as causative agents may be encountered as a result of developments in identification methods. In the few publications in the literature where A.flavus complex was reported as the causative agent of joint infections, it seems possible that some of the agents may be A.flavus and some may be A.oryzae, since the agents were identified at the complex level. There are a limited number of cases in the literature where A.oryzae is the causative agent, particularly in the respiratory tract. A PubMed search using the keywords \"A.oryzae infections, arthritis, osteomyelitis\" did not reveal any literature on joint infections caused by A.oryzae.

The authors report a singular case of post-operative exogenous fungal endophthalmitis caused by a non-pathogenic fungal agent: Aspergillus oryzae. A 75-year-old Caucasian woman with post-penetrating keratoplasty fungal endophthalmitis due to a nonpathogenic A. oryzae, resistant to the current azoles anti-fungal agents, was treated with subtotal vitrectomy, intravitreal injection, and systemic voriconazole therapy. Complete resolution of the endophthalmitis occurred after two subsequent intravitreal injections and a 2-month-long systemic delivery of voriconazole. The quick identification of the fungal agent allowed immediate and targeted therapy. In the article, the safety and efficacy of both systemic and intravitreal voriconazole treatments are discussed.

A-55-year-old man who have been working in a Sake (Japanese rice wine) brewer for 27 years, came to the outpatient clinic because cough, dyspnea, and wheeze gradually worsen. These symptoms occurred immediately after exposure to Aspergillus oryzae in the brewing process since age 43. A dust mask was required to reduce these symptoms, but that work was interrupted by exacerbation of these symptoms. These symptoms disappeared when he was away from the on-site work. The SMART therapy using combined inhaler of budesonide (ICS) with formoterol (LABA) was effective to reduce these symptoms. In serological test total IgE antibody and Aspergillus specific IgE antibodies increased, whereas Aspergillus precipitating antibody and Asp f 1 (a major allergen of Aspergillus fumigatus) specific IgE antibody were negative. Eosinophilia in peripheral blood was not observed, and FeNO was not increased. Values of peak expiratory flow was reduced by 20.8% after exposure to Aspergillus oryzae in that work. Lung function test including reversibility test was intact, but FEV1 was fluctuated up to 400mL (15.9%) in the clinical course. Based on these variable clinical manifestations, laboratory data, and lung function test findings, this case was diagnosed as adult-onset atopic (Aspergillus-sensitized) bronchial asthma without allergic bronchopulmonary aspergillosis. Involvement of eosinophilic inflammation is unknown. Allergen may be considered to be Aspergillus oryzae, because these symptoms do not occur in any environment without exposure to Aspergillus oryzae. This patient is the first case of occupational asthma related to Aspergillus oryzae in a Japanese rise wine brewer.

The filamentous fungus Aspergillus oryzae is used in soy sauce koji making due to its high productivity of hydrolytic enzymes. In this study, we compared the genomes and transcriptomes of an industrial strain RD2 and a strain with decreased fermentation performance TS2, aiming to explain their phenotypic differences at the molecular level. Under the regulation of conidiation and fermentation conditions, the enhanced hydrolytic enzyme production and flavor precursor formation in RD2 described a complete expression profile necessary to maintain desirable fermentation performance. By contrast, central carbon metabolism was up-regulated in TS2 for fast growth, suggesting a conflicting relationship between mycelium growth and fermentation performance. Accumulation of mutations also lowered the fermentation performance of TS2. Our study has deepened the understanding of the metabolism and related regulatory mechanisms in desirable koji fermentation. A list of potential molecular markers identified here could facilitate targeted strain maintenance and improvement for better koji fermentation.

Infective endocarditis (IE) is a severe disease with high mortality and morbidity. Prosthetic valve endocarditis is a life-threatening complication which can occur in less than 10% of patients with valve prosthesis. A fungal etiology of IE is rare and accounts for only 2-4% of all case of endocarditis, but is associated with a higher mortality and morbidity. Herein is reported the first case of fungal endocarditis of aortic valve prosthesis due to Aspergillus oryzae in a 67-year-old caucasian man who nine years previously underwent mitral and aortic valve replacement with mechanical prostheses, and tricuspid annuloplasty for acute IE due to Enterococcus spp. Seven months previously, the patient also underwent a redo cardiac procedure to replace a mitral valve prosthesis with a new mechanical device due to a leakage. Aspergillus oryzae showed impressive growth with strong and unexpected virulence in both local and systemic settings.

Aspergillus oryzae is widely used for the industrial production of enzymes. In A. oryzae metabolism, transporters appear to play crucial roles in controlling the flux of molecules for energy generation, nutrients delivery, and waste elimination in the cell. While the A. oryzae genome sequence is available, transporter annotation remains limited and thus the connectivity of metabolic networks is incomplete. In this study, we developed a metabolic annotation strategy to understand the relationship between the sequence, structure, and function for annotation of A. oryzae metabolic transporters. Sequence-based analysis with manual curation showed that 58 genes of 12,096 total genes in the A. oryzae genome encoded metabolic transporters. Under consensus integrative databases, 55 unambiguous metabolic transporter genes were distributed into channels and pores (7 genes), electrochemical potential-driven transporters (33 genes), and primary active transporters (15 genes). To reveal the transporter functional role, a combination of homology modeling and molecular dynamics simulation was implemented to assess the relationship between sequence to structure and structure to function. As in the energy metabolism of A. oryzae, the H(+)-ATPase encoded by the AO090005000842 gene was selected as a representative case study of multilevel linkage annotation. Our developed strategy can be used for enhancing metabolic network reconstruction.

Fungal peritonitis is a rare, but serious, complication of continuous ambulatory peritoneal dialysis (CAPD). We report a case of peritonitis caused by Aspergillus oryzae in a man on CAPD therapy who was treated successfully with amphotericin B and caspofungin, followed by itraconazole and removal of the peritoneal catheter. A oryzae was identified by using sequence analysis of the ribosomal DNA genes. Of 10 reported cases since 2003, the mortality rate was 30%. Removal of the CAPD catheter and systemic antimycotic therapy are essential to achieve clinical cure in patients with fungal CAPD-related peritonitis.

A 29-year-old female bakery shop assistant was occupationally sensitized to flour allergens and Aspergillus alpha-amylase (Asp o 2). The latter represents a strongly allergenic component of routinely used baking additives. The patient had repeatedly responded to the consumption of white bread with rhinitis, conjunctivitis, and, occasionally, wheal and flare reactions. She underwent allergologic investigations including oral challenge tests with commercially available bread loaves. Elevated specific IgE antibodies against bread extracts, Asp o 2, and flour allergens were detectable in her serum. The provocation test with bread resulted in a running nose together with a strong increase in nasal resistance. All symptoms subsided about 3 h after the challenge. None of the above symptoms could be observed when bread free of Aspergillus alpha-amylase was administered. This outcome provides evidence of a clinically relevant persistent allergenicity to Asp o 2 in bread.

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