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Involvement of the opportunistic pathogen Aspergillus tubingensis in osteomyelitis of the maxillary bone: a case report.

ABSTRACT: BACKGROUND: Aspergillus tubingensis is a black Aspergillus belonging to the Aspergillus section Nigri, which includes species that morphologically resemble Aspergillus niger. Recent developments in species determination have resulted in clinical isolates presumed to be Aspergillus niger being reclassified as Aspergillus tubingensis by sequencing. We present a report of a patient with an osteomyelitis of the maxillary bone with a probable invasive Aspergillus tubingensis infection. CASE PRESENTATION: We describe an immune compromised patient suffering from osteomyelitis of the maxillary bone after tooth extraction. The osteomyelitis probably resulted in dentogenic pansinusitis presenting as an acute ethmoiditis. Histologic examination of biopsy samples showed osteomyelitis, and inflammation of the surrounding connective tissue. Cultures of the alveolar wound grew Aspergillus tubingensis. The patient was treated with liposomal amphoterocin B, which was changed to oral treatment with voriconazole based on susceptibility testing (MIC for voriconazole was 1 ?g/ml). CONCLUSION: This case shows that Aspergillus tubingensis may have the potential to cause severe invasive infections in immunocompromised hosts. A larger proportion of Aspergillus tubingensis isolates are less susceptible to azoles compared to Aspergillus niger. Therefore, correct species identification and susceptibility testing is crucial for the choice of anti-fungal treatment, screening of azole resistance, and characterization of the pathogenic potential of the various species within Aspergillus section Nigri.

SUBMITTER: Bathoorn E

PROVIDER: S-EPMC3565948 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Involvement of the opportunistic pathogen Aspergillus tubingensis in osteomyelitis of the maxillary bone: a case report.

Bathoorn Erik E Escobar Salazar Natalia N Sepehrkhouy Shahrzad S Meijer Martin M de Cock Hans H Haas Pieter-Jan PJ

BMC infectious diseases 20130201

<h4>Background</h4>Aspergillus tubingensis is a black Aspergillus belonging to the Aspergillus section Nigri, which includes species that morphologically resemble Aspergillus niger. Recent developments in species determination have resulted in clinical isolates presumed to be Aspergillus niger being reclassified as Aspergillus tubingensis by sequencing. We present a report of a patient with an osteomyelitis of the maxillary bone with a probable invasive Aspergillus tubingensis infection.<h4>Case ...[more]

PMID: 23374883

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Project description:BackgroundDespite of the presence of sulfhydryl oxidases (SOXs) in the secretomes of industrially relevant organisms and their many potential applications, only few of these enzymes have been biochemically characterized. In addition, basic functions of most of the SOX enzymes reported so far are not fully understood. In particular, the physiological role of secreted fungal SOXs is unclear.ResultsThe recently identified SOX from Aspergillus tubingensis (AtSOX) was produced, purified and characterized in the present work. AtSOX had a pH optimum of 6.5, and showed a good pH stability retaining more than 80% of the initial activity in a pH range 4-8.5 within 20 h. More than 70% of the initial activity was retained after incubation at 50 °C for 20 h. AtSOX contains a non-covalently bound flavin cofactor. The enzyme oxidised a sulfhydryl group of glutathione to form a disulfide bond, as verified by nuclear magnetic resonance spectroscopy. AtSOX preferred glutathione as a substrate over cysteine and dithiothreitol. The activity of the enzyme was totally inhibited by 10 mM zinc sulphate. Peptide- and protein-bound sulfhydryl groups in bikunin, gliotoxin, holomycin, insulin B chain, and ribonuclease A, were not oxidised by the enzyme. Based on the analysis of 33 fungal genomes, SOX enzyme encoding genes were found close to nonribosomal peptide synthetases (NRPS) but not with polyketide synthases (PKS). In the phylogenetic tree, constructed from 25 SOX and thioredoxin reductase sequences from IPR000103 InterPro family, AtSOX was evolutionary closely related to other Aspergillus SOXs. Oxidoreductases involved in the maturation of nonribosomal peptides of fungal and bacterial origin, namely GliT, HlmI and DepH, were also evolutionary closely related to AtSOX whereas fungal thioreductases were more distant.ConclusionsAtSOX (55 kDa) is a fungal secreted flavin-dependent enzyme with good stability to both pH and temperature. A Michaelis-Menten behaviour was observed with reduced glutathione as a substrate. Based on the location of SOX enzyme encoding genes close to NRPSs, SOXs could be involved in the secondary metabolism and act as an accessory enzyme in the production of nonribosomal peptides.

Project description:Aspergillus nidulans is an opportunistic fungal pathogen in patients with immunodeficiency, and virulence of A. nidulans isolates has mainly been studied in the context of chronic granulomatous disease (CGD), with characterization of clinical isolates obtained from non-CGD patients remaining elusive. This study therefore carried out a detailed biological characterization of two A. nidulans clinical isolates (CIs), obtained from a patient with breast carcinoma and pneumonia and from a patient with cystic fibrosis that underwent lung transplantation, and compared them to the reference, nonclinical FGSC A4 strain. Both CIs presented increased growth in comparison to that of the reference strain in the presence of physiologically relevant carbon sources. Metabolomic analyses showed that the three strains are metabolically very different from each other in these carbon sources. Furthermore, the CIs were highly susceptible to cell wall-perturbing agents but not to other physiologically relevant stresses. Genome analyses identified several frameshift variants in genes encoding cell wall integrity (CWI) signaling components. Significant differences in CWI signaling were confirmed by Western blotting among the three strains. In vivo virulence studies using several different models revealed that strain MO80069 had significantly higher virulence in hosts with impaired neutrophil function than the other strains. In summary, this study presents detailed biological characterization of two A. nidulanssensu stricto clinical isolates. Just as in Aspergillus fumigatus, strain heterogeneity exists in A. nidulans clinical strains that can define virulence traits. Further studies are required to fully characterize A. nidulans strain-specific virulence traits and pathogenicity.IMPORTANCE Immunocompromised patients are susceptible to infections with opportunistic filamentous fungi from the genus Aspergillus Although A. fumigatus is the main etiological agent of Aspergillus species-related infections, other species, such as A. nidulans, are prevalent in a condition-specific manner. A. nidulans is a predominant infective agent in patients suffering from chronic granulomatous disease (CGD). A. nidulans isolates have mainly been studied in the context of CGD although infection with A. nidulans also occurs in non-CGD patients. This study carried out a detailed biological characterization of two non-CGD A. nidulans clinical isolates and compared the results to those with a reference strain. Phenotypic, metabolomic, and genomic analyses highlight fundamental differences in carbon source utilization, stress responses, and maintenance of cell wall integrity among the strains. One clinical strain had increased virulence in models with impaired neutrophil function. Just as in A. fumigatus, strain heterogeneity exists in A. nidulans clinical strains that can define virulence traits.

Dataset Information

Involvement of the opportunistic pathogen Aspergillus tubingensis in osteomyelitis of the maxillary bone: a case report.

Publications

Involvement of the opportunistic pathogen Aspergillus tubingensis in osteomyelitis of the maxillary bone: a case report.

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