Pesticide behavior in paddy fields and development of azole-resistant Aspergillus fumigatus : Should we be concerned?

Vaezi, Afsane; Fakhim, Hamed; Javidnia, Javad; Khodavaisy, Sadegh; Abtahian, Zahra; Vojoodi, M; Nourbakhsh, Fahimeh; Badali, Hamid

doi:10.1016/j.mycmed.2017.12.007

Cited by 32 publications

(27 citation statements)

References 31 publications

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“…Remarkably, this tight association of the 23 bp CYP51A promoter deletion with the high VRC resistance phenotype of group II isolates reached across species boundaries and was independent of their clinical (e.g., Nk2781, NkDI17) or environmental (e.g., Nk994, NkDir61) origin (Figure 4). Similar promoter mutations resulted in pan-azole, including VRC, resistance (Wiederhold et al, 2016) in clinical A. fumigatus isolates that were possibly selected for by excessive agricultural use of azole antifungals (Chowdhary et al, 2013;Faria-Ramos et al, 2014;Vaezi et al, 2018). Unfortunately, we were not able to confirm an association between VRC resistance and the 23 bp CYP51A promoter deletion in all N. falciformis isolates, for technical reasons.…”

Section: Cyp51a Cyp51b Cyp51cmentioning

confidence: 82%

“…The increasing incidence of IFs (Lortholary et al, 2010;Nucci et al, 2013;Tortorano et al, 2014) and reports of azole resistance caused by the widespread use of azole fungicides in agriculture (Chowdhary et al, 2013;Faria-Ramos et al, 2014;Vaezi et al, 2018) prompted us to study possible azole resistance mechanisms in Neocosmospora species of the FSSC.…”

Section: Introductionmentioning

confidence: 99%

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A 23 bp cyp51A Promoter Deletion Associated With Voriconazole Resistance in Clinical and Environmental Isolates of Neocosmospora keratoplastica

et al. 2020

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In the fungal pathogen Aspergillus fumigatus, resistance to azole antifungals is often linked to mutations in CYP51A, a gene that encodes the azole antifungal drug target lanosterol 14α-demethylase. The aim of this study was to investigate whether similar changes could be associated with azole resistance in a Malaysian Fusarium solani species complex (FSSC) isolate collection. Most (11 of 15) clinical FSSC isolates were Neocosmospora keratoplastica and the majority (6 of 10) of environmental isolates were Neocosmospora suttoniana strains. All 25 FSSC isolates had high minimum inhibitory concentrations (MICs) for itraconazole and posaconazole, low MICs for amphotericin B, and various (1 to >32 mg/l) voriconazole susceptibilities. There was a tight association between a 23 bp CYP51A promoter deletion and high (>32 mg/l) voriconazole MICs; of 19 FSSC strains sequenced, nine isolates had voriconazole MICs > 32 mg/l, and they all contained the 23 bp CYP51A promoter deletion, although it was absent in the ten remaining isolates with low (≤12 mg/l) voriconazole MICs. Surprisingly, this association between voriconazole resistance and the 23 bp CYP51A promoter deletion held true across species boundaries. It was randomly distributed within and across species boundaries and both types of FSSC isolates were found among environmental and clinical isolates. Three randomly selected N. keratoplastica isolates with low (≤8 mg/l) voriconazole MICs had significantly lower (1.3-7.5 times) CYP51A mRNA expression levels than three randomly selected N. keratoplastica isolates with high (>32 mg/l) voriconazole MICs. CYP51A expression levels, however, were equally strongly induced (∼6,500-fold) by voriconazole in two representative strains reaching levels, after 80 min of induction, that were comparable to those of CYP51B. Our results suggest that FSSC isolates with high voriconazole MICs have a 23 bp CYP51A promoter deletion that provides a potentially useful marker for voriconazole resistance in FSSC isolates. Early detection of possible voriconazole resistance is critical for choosing the correct treatment option for patients with invasive fusariosis.

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Section: Cyp51a Cyp51b Cyp51cmentioning

confidence: 82%

Section: Introductionmentioning

confidence: 99%

A 23 bp cyp51A Promoter Deletion Associated With Voriconazole Resistance in Clinical and Environmental Isolates of Neocosmospora keratoplastica

et al. 2020

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“…In recent years, an increased incidence of invasive aspergillosis (IA) has affected the lives of many immunocompromised patients [1]. It has been reported that some Aspergillus strains are resistant to azoles, polyenes and echinocandins, thus reducing the effectiveness of treatments [2]. Combinations of azoles and echinocandins against Aspergillus or azole-resistant Aspergillus are known to be effective for the treatment of serious infections [2,3].…”

Section: Introductionmentioning

confidence: 99%

“…It has been reported that some Aspergillus strains are resistant to azoles, polyenes and echinocandins, thus reducing the effectiveness of treatments [2]. Combinations of azoles and echinocandins against Aspergillus or azole-resistant Aspergillus are known to be effective for the treatment of serious infections [2,3]. Moreover, new imidazoles, such as lanoconazole and luliconazole, strongly inhibit the growth of Aspergillus spp.…”

Section: Introductionmentioning

confidence: 99%

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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“…However, new combinational therapies with clinically licensed drugs against fungal infections are being tested as potential alternatives (Fakhim et al 2018). The most recent concern about Aspergillus, especially A. fumigatus sensu stricto, is the emergence of acquired azole-resistance due to the high usage of azoles fungicides in agriculture and in an extensive range of construction materials, generating a positive selective pressure of azole-resistant strains (Vaezi et al 2018b), which may lead to therapeutic fails in case of infection. Thus, the indoor exposure to Aspergillus and especially to less susceptible or resistant isolates may pose a difficult medical problem in the management of patients with aspergillosis Snelders et al 2012;Kleinkauf et al 2013;Prigitano et al 2014;Perlin et al 2017).…”

Section: Introductionmentioning

confidence: 99%

Aspergillus collected in specific indoor settings: their molecular identification and susceptibility pattern

Simões

Caetano

Veríssimo

et al. 2019

International Journal of Environmental Health Research

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Exposure to Aspergillus conidia is an increased risk factor for the development of respiratory symptoms. The emergence of azole resistance in Aspergillus fumigatus is a major concern for the scientific community. The aim of this study was to perform the molecular identification of Aspergillus species collected from different occupational and nonoccupational indoor settings and to study the azole susceptibility profile of the collected Fumigati isolates. The selected Aspergillus isolates were identified as belonging to the sections Fumigati, Nigri Versicolores, Terrei, Clavati and Nidulantes. All the Aspergillus fumigatus were screened for azole resistance using an agar media supplemented with itraconazole, voriconazole and posaconazole. None of the tested isolates showed resistance to those azoles. Knowledge of Aspergillus epidemiology in specific indoor environments allows a better risk characterization regarding Aspergillus burden. This study allowed the analysis of the molecular epidemiology and the determination of the susceptibility pattern of Aspergillus section Fumigati found in the studied indoor settings. ARTICLE HISTORY

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Pesticide behavior in paddy fields and development of azole-resistant Aspergillus fumigatus : Should we be concerned?

Cited by 32 publications

References 31 publications

A 23 bp cyp51A Promoter Deletion Associated With Voriconazole Resistance in Clinical and Environmental Isolates of Neocosmospora keratoplastica

A 23 bp cyp51A Promoter Deletion Associated With Voriconazole Resistance in Clinical and Environmental Isolates of Neocosmospora keratoplastica

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

Aspergillus collected in specific indoor settings: their molecular identification and susceptibility pattern

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