Chronic Illness Associated with Mold and Mycotoxins:  Is Naso-Sinus Fungal Biofilm the Culprit?

Brewer, Joseph H.; Thrasher, Jack D.; Hooper, Dennis G.

doi:10.3390/toxins6010066

Cited by 22 publications

(14 citation statements)

References 77 publications

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“…In vivo findings show that in sinus aspergillomas, A. fumigatus may grow as a typical biofilm characterized by hyphae anchored within an extracellular matrix. Similar biofilms have also been observed on contact lenses in fungal keratitis, in bronchoalveolar lavage fluids of chronic pulmonary aspergillosis and in neutropenic cancer patients with IA [6,7]. Without adequate therapy, these diseases result in long-term suffering of patients.…”

Section: Introductionsupporting

confidence: 61%

Synergistic effects of vorinostat (SAHA) and azoles against Aspergillus species and their biofilms

Yin

2020

BMC Microbiol

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Background: Invasive aspergillosis is a fungal infection that occurs mainly in immunocompromised patients. It is responsible for a high degree of mortality and is invariably unresponsive to conventional antifungal treatments. Histone deacetylase inhibitors can affect the cell cycle, apoptosis and differentiation. The histone deacetylase inhibitor vorinostat (SAHA) has recently received approval for the treatment of cutaneous T cell lymphoma. Here, we investigated the interactions of SAHA and itraconazole, voriconazole, and posaconazole against Aspergillus spp. in vitro using both planktonic cells and biofilms. Results: We investigated 20 clinical strains using broth microdilution checkerboard methods. The results showed synergy between SAHA and itraconazole, voriconazole, and posaconazole against 60, 40, and 25% of tested isolates of planktonic Aspergillus spp., respectively. Similar synergy was also observed against Aspergillus biofilms. The expression of the azole-associated multidrug efflux pumps MDR1, MDR2, MDR3 and MDR4, as well as that of HSP90, was measured by RT-PCR. The results indicated that the molecular mechanism of the observed synergistic effects in Aspergillus fumigatus may be partly associated with dampened expression of the efflux pump genes and, furthermore, that HSP90 suppression may be a major contributor to the observed synergistic effects of the drugs.Conclusions: SAHA has potential as a secondary treatment to enhance the effects of azoles against both biofilm and planktonic cells of Aspergillus spp. in vitro. This effect occurs mostly by inhibition of HSP90 expression.

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Section: Introductionsupporting

confidence: 61%

Synergistic effects of vorinostat (SAHA) and azoles against Aspergillus species and their biofilms

Yin

2020

BMC Microbiol

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“…Living and/or working in a water-damage building has been associated with the presence of toxicogenic fungi and of their mycotoxins (especially aflatoxin, ochratoxin and trichothecenes) in nasal wash and with an increased concentration of mycotoxins in urine [135,136]. Mycotoxin toxicity may be aggravated by the formation of fungal biofilm in sinus [137].…”

Section: Chronic Mycotoxicosis and Other Pathologies Associated With mentioning

confidence: 99%

“…Mycotoxin toxicity may be aggravated by the formation of fungal biofilm in sinus [137]. Mycotoxins have also been shown to accumulate in lungs, spleen and lymph nodes [135], as well as in placenta, umbilical cord blood and breast milk in symptomatic pregnant women, which might be responsible for side effects on fetus or new-born [138]. Despite the established deletary role of mycotoxins in animal models, epidemiological evidences struggle to establish a link between mycotoxins and respiratory health effects.…”

Section: Chronic Mycotoxicosis and Other Pathologies Associated With mentioning

confidence: 99%

Immune responses to airborne fungi and non-invasive airway diseases

2014

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Inhalation of fungal particles is a ubiquitous way of exposure to microorganisms during human life; however, this exposure may promote or exacerbate respiratory diseases only in particular exposure conditions and human genetic background. Depending on the fungal species and form, fungal particles can induce symptoms in the lung by acting as irritants, aeroallergens or pathogens causing infection. Some thermophilic species can even act in all these three ways (e.g. Aspergillus, Penicillium), mesophilic species being only involved in allergic and/or non-allergic airway diseases (e.g. Cladosporium, Alternaria, Fusarium). The goal of the present review is to present the current knowledge on the interaction between airborne fungal particles and the host immune system, to illustrate the differences of immune sensing of different fungal species and to emphasise the importance of conducting research on non-conventional mesophilic fungal species. Indeed, the diversity of fungal species we inhale and the complexity of their composition have a direct impact on fungal particle recognition and immune system decision to tolerate or respond to those particles, eventually leading to collateral damages promoting airway pathologies.

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“…Aflatoxins and Ochratoxin A ( Figure 1 & Figure 2) [1], persistent and thermostable natural mycotoxins produced by fungi [2] [3], are found in different foodstuffs such as peanuts, corn, coffee beans and spices [4]. Aflatoxins are composed mainly of G2, B2, G1 andB1toxins; the latter has been classified as a carcinogen [5].…”

Section: Introductionmentioning

confidence: 99%

Challenging the Expiry Dates of Two Mycotoxins Standards: Afla and Ochra A

Aridi¹,

Baydoun²,

Sukhn³

2017

MSCE

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Objectives: To challenge the expiry dates of low concentration high purity mycotoxins standards. Literature Review: Aflatoxins (AFs) and Ochratoxin A (OTA) are persistent mycotoxins with adverse effects on humans. Mycotoxins standards are purchased to determine mycotoxin concentrations in food and may be stocked in some laboratories beyond expiry dates causing laboratories financial losses. Methods: Certified mycotoxins standards were purchased over the years from the same supplier at times and at other times from two different suppliers for quality control purposes. For AFs, six chromatographic runs for each of the mycotoxins standards were done to compare the difference among these standards having the following expiry dates (2008, 2012, 2013 and 2018). AFs standards purchased/obtained from two different suppliers in 2016 and expiring in 2018 were also compared. For OTA, the difference of concentration obtained between two years (2010 and 2018) was tested. All samples were run on a HPLC equipped with a fluorescence detector. Linearity of calibration curves and the points of lowest detection were determined for AFs components and for OTA from the unexpired mycotoxins standards. Results: At a 0.05 significance level and using non parametric tests, the statistical test revealed a p of 0.166, 0.153, 0.358 and 0.03 for B1, G1, B2 and G2 respectively among years for standards from same supplier and 0.037, 0.109, 0.182 and 0.182 for B1, G1, B2 and G2 respectively for unexpired standards from two different suppliers. For OTA, a p of 0.109 was obtained for standards of different expiry dates purchased from different suppliers. Conclusion: High purity low concentration mycotoxin standards purchased a decade ago (i.e. expired) did not differ from those purchased this current year (still valid). Hence, the expiry date can be renewed reducing the laboratories expenses. Manufacturers are urged to reconsider the expiry dates.

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Chronic Illness Associated with Mold and Mycotoxins: Is Naso-Sinus Fungal Biofilm the Culprit?

Cited by 22 publications

References 77 publications

Synergistic effects of vorinostat (SAHA) and azoles against Aspergillus species and their biofilms

Synergistic effects of vorinostat (SAHA) and azoles against Aspergillus species and their biofilms

Immune responses to airborne fungi and non-invasive airway diseases

Challenging the Expiry Dates of Two Mycotoxins Standards: Afla and Ochra A

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