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Plenodomus lingam (Leptosphaeria maculans) and P. biglobosus (L. biglobosa) are fungi causing Phoma leaf spot/stem canker, an international damaging disease of oilseed rape (Brassica napus) and other brassicas. In Europe, fungicides used for disease management are mainly sterol 14α‐demethylase (CYP51) inhibitors (DMIs/azoles); quinone‐outside inhibitors (QoIs) and succinate dehydrogenase inhibitors (SDHIs) are also used. Decreased DMI sensitivity has emerged in Australian and eastern European P. lingam populations and is mediated by CYP51 promoter inserts resulting in target site overexpression. In this study using in vitro sensitivity testing, we report decreased DMI (prothioconazole‐desthio, mefentrifluconazole) sensitivity in modern western European P. lingam isolates (collected 2022–2023) compared to older baseline (1992–2005) isolates. Around 85% of modern western European P. lingam isolates collected, for which the CYP51 promoter region was sequenced, carried a promoter insert, but target site alterations were not detected. Six different CYP51 promoter inserts were identified, most commonly a 237 bp fragment of the Sahana transposable element. Inserts were associated with an approximately 3‐ to 10‐fold decrease in sensitivity to the DMIs tested. In contrast to P. lingam, PCR screening revealed CYP51 promoter inserts were absent in modern western European P. biglobosus isolates (2021–2023). Combined data indicate P. lingam isolates lacking an insert were similarly (or slightly more) sensitive to the DMIs tested for P. biglobosus, whereas those carrying an insert were slightly less sensitive than P. biglobosus. No evidence for substantive sensitivity shifts to the QoI (pyraclostrobin) or SDHI (boscalid) fungicides tested was obtained for either Plenodomus species. [ABSTRACT FROM AUTHOR]

Acclimatized fungal diseases in wheat crops pose a severe threat to world wheat production. Zymoseptoria tritici, which causes Septoria tritici blotch (STB), is known as a devastating latent necrotrophic fungal pathogen that causes a significant yield loss, especially in Europe and in other wheat-growing countries. This fungal pathogen developed rapid resistance against new and old fungicides and has become a major threat to future wheat crops. Strobilurines and Azoles are the main group of contact and systemic fungicides along with succinate dehydrogenase inhibitors with reliable results to control the Z. tritici all over the world. However, many reports from Europe described the presence of resistance in Z. tritici against these fungicides. In the present study, a total of 102 isolates of Z. tritici were collected from five regions (Central Anatolia, Southeastern Anatolia, Marmara, Aegean, and the Mediterranean) of 19 provinces of Turkey to check the presence of target-site mutation at a molecular level to these two main fungicides. Azole target-site mutation in the CYP51 gene was checked by sanger sequencing while the strobilurin resistance mutation in the Cytb gene was confirmed by using PCR–RFLP using the FnuHI restriction enzyme. The obtained results from the two genes revealed some target-site mutations, however no known amino acid changes that cause resistance against these two main group fungicides in Turkish isolates have been detected. We concluded that the severe infection of STB pathogen in Turkish wheat growing may be still manageable with these fungicides although the resistance tests must be conducted for certainity. [ABSTRACT FROM AUTHOR]

Definition: Ramularia leaf spot (RLS), caused by the fungus Ramularia collo-cygni, has recently become widespread in Europe. Succinate dehydrogenase inhibitor (SDHI) and demethylation inhibitor (DMI) fungicides are mainly applied for disease control on barley fields, but pathogen isolates with a reduced sensitivity can cause difficulties. There is an urgent need for new spring barley cultivars that are more resistant to RLS development and can inhibit R. collo-cygni epidemics. [ABSTRACT FROM AUTHOR]

Septoria tritici blotch (STB; Zymoseptoria tritici) is the most important leaf disease of wheat in Northern and Western Europe. The problem of fungicide resistance in Z. tritici populations is challenging future control options. In order to investigate differences in azole performances against STB, 55 field trials were carried out during four seasons (2015–2018). These trials were undertaken in ten different countries across Europe covering a diversity of climatic zones and agricultural practices. During all four seasons, four single azoles (epoxiconazole, prothioconazole, tebuconazole and metconazole) were tested. Increasing variability in the performances of these azoles against STB was observed across Europe. The efficacy of the tested azoles varied considerably across the continent and between countries. The shifts in disease control from these commonly used azoles were confirmed by increasing EC50 values for epoxiconazole, prothioconazole-desthio and metconazole. The sensitivity towards tebuconazole remained relatively low across the four years. The frequencies of CYP51 mutations varied substantially across Europe, with a clear pattern of significantly decreasing frequencies of D134G, V136A and S524T in the local Z. tritici populations from west to east. In contrast, no major differences were seen for CYP51 mutations V136C, A379 and I381V. The four azoles showed different levels of cross-resistance, which again depended on specific CYP51 mutations. Across the four seasons, the single azoles increased the yields between 9 and 11% on average. [ABSTRACT FROM AUTHOR]

Azole resistance in Aspergillus fumigatus (AFM) is increasing and often associated with cyp51 alterations. We evaluated the activity of isavuconazole and other mold-active azoles against 731 AFM isolates causing invasive aspergillosis collected in Europe (EU; n = 449) and North America (NA; n = 282). Isolates were submitted to CLSI susceptibility testing and epidemiological cutoff value (ECV) criteria. A posaconazole ECV of 0.5 mg/L was used as no CLSI ECV was determined. Azole non-wild-type (NWT) isolates were submitted for cyp51 sequencing by whole genome sequencing. Overall, isavuconazole activity (92.7%/94.0% WT in EU/NA) was comparable to other azoles (WT rate range, 90.9%-96.4%/91.8%-98.6%, respectively), regardless of the region. A total of 79 (10.8%) azole NWT isolates were detected, and similar rates of these isolates were noted in EU (10.7%) and NA (11.0%). Although most AFM were WT to azoles, increasing azole NWT rates were observed in NA (from 6.0% in 2017 to 29.3% in 2021). Azole NWT rates varied from 4.9% (2019) to 20.6% (2018) in EU without an observed trend. cyp51 alterations occurred in 56.3%/54.8% of azole NWT from EU/NA, respectively. The cyp51A TR 34 /L98H alteration was observed only in EU isolates (72.0% of EU isolates), while cyp51A I242V occurred only in NA isolates (58.3%). Isavuconazole remained active (MIC, ≤1 mg/L) against 18.5/47.1% of azole NWT AFM exhibiting cyp51 alterations in EU/NA, along with voriconazole (29.6/82.4%; MIC, ≤1 mg/L) and posaconazole (48.1/88.2%; MIC, ≤0.5 mg/L). Fourteen different cyp51 alterations were detected in 44 of 79 NWT isolates. The in vitro activity of the azoles varied in AFM that displayed cyp51 alterations. IMPORTANCE A few microbiology laboratories perform antifungal susceptibility testing locally for systemically active antifungal agents. The identification of emerging azole-resistant Aspergillus fumigatus is worrisome. As such, there is a critical role for antifungal surveillance in tracking emerging resistance among both common and uncommon opportunistic fungi. Differences in the regional prevalence and antifungal resistance of these fungi render local epidemiological knowledge essential for the care of patients with a suspected invasive fungal infection., Competing Interests: The authors declare no conflict of interest.

Azoles reacting in tandem: The ortho‐stereodirecting effect is the key to the stereoselective synthesis of (Z)‐N‐alkenylazoles I through the tosylhydrazide‐mediated Pd‐catalyzed cross‐coupling reaction of α‐N‐azoleacetophenones with ortho‐substituted aryl halides and nonaflates (see scheme). Additionally, the preorganization of the alkene allowed for the development of an auto‐tandem reaction involving an intramolecular CH arylation leading to pyrroloisoquinolines II. [ABSTRACT FROM AUTHOR]

This review summarises recent investigations into the molecular mechanisms responsible for the decline in sensitivity to azole (imidazole and triazole) fungicides in European populations of the Septoria leaf blotch pathogen, Mycosphaerella graminicola. The complex recent evolution of the azole target sterol 14α-demethylase (MgCYP51) enzyme in response to selection by the sequential introduction of progressively more effective azoles is described, and the contribution of individual MgCYP51 amino acid alterations and their combinations to azole resistance phenotypes and intrinsic enzyme activity is discussed. In addition, the recent identification of mechanisms independent of changes in MgCYP51 structure correlated with novel azole cross-resistant phenotypes suggests that the further evolution of M. graminicola under continued selection by azole fungicides could involve multiple mechanisms. The prospects for azole fungicides in controlling European M. graminicola populations in the future are discussed in the context of these new findings. Copyright © 2012 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Azole-resistant strains of Aspergillus have been reported from European and Asian countries at varying frequencies. Based on the limited rates of isolation of Aspergillus from clinical samples in routine practice and the limited number of the screening studies carried out so far, the true prevalence of triazole resistance and the rate of multiazole-resistant strains remain partly unknown. Also, available data are mostly for A. fumigatus (complex), thus the situation for non- fumigatus Aspergilli is less clear. In general, exposure of Aspergillus to antifungal agents via medical or environmental (agricultural) use of these compounds appears to have the possible major impact on acquisition of triazole resistance. Azole resistance in Aspergillus remains to be further elucidated by continued surveillance studies. Based on the possible association with agricultural azole use, environmental sampling appears significant as well. [ABSTRACT FROM AUTHOR]

The article offers information on Azole fungicides which are used to control the septoria leaf blotch microorganism in wheat, a foliar disease of mycosphaerella graminicola. It states that mycosphaerella graminicola is a wheat plant pathogen that has evolved resistance to fungicides. Furthermore, Azole fungicides are the most effective agents in controlling fungal pathogens for both humans and plants in Great Britain and Europe.

• Over 2,000 moulds collected worldwide from 2010−2017 were susceptibility tested. • Azoles displayed 98.7% categorical agreement when tested against A. fumigatus. • Azole non-wildtype rates of A. fumigatus were higher in Europe. • Azole non-wildtype A. fumigatus increased in Europe from 0% to 5% in 2017. • Posaconazole and amphotericin B were the most active agents against Mucorales. The epidemiology of invasive filamentous fungal diseases requires monitoring due to changes in susceptibility patterns of new and established antifungal agents that may affect clinical practices. We evaluated the activity of posaconazole against 2,157 invasive moulds collected worldwide from 2010−2017. The isolates included 1,775 Aspergillus spp. and 382 non- Aspergillus moulds, including 81 Fusarium spp., 62 Mucorales group, and 57 Scedosporium spp. Isolates were tested using the CLSI reference broth microdilution method. Posaconazole showed similar activity to itraconazole and voriconazole against A. fumigatus. Applying published ECV, 98.0% of the A. fumigatus and 97.7% to 100.0% of other common Aspergillus species were wildtype to posaconazole. Categorical agreement between posaconazole and the other azoles tested against A. fumigatus was 98.7%. Notably, most of the Aspergillus spp. isolates recovered from this large collection were wildtype to echinocandins and all azoles. Posaconazole non-wildtype rates of A. fumigatus varied across the different geographic regions, with 2.1% in Europe, 2.2% in North America, 1.8% in Latin America, and 0.7% in the Asia-Pacific region. The frequency of azole non-wildtype A. fumigatus isolates from Europe increased steadily from 2010−2017 for all 3 triazoles (0.0%−5.0%). The azole non-wildtype A. fumigatus rates from the other geographic areas were stable over time. Fusarium and/or Scedosporium spp. isolates were highly resistant to azoles and echinocandins. Posaconazole and amphotericin B were the most active agents against the Mucorales. Posaconazole was very active against most species of Aspergillus and was comparable to itraconazole and voriconazole against the less common moulds. Posaconazole should provide a useful addition to the anti-mould grouping of antifungal agents. [ABSTRACT FROM AUTHOR]

The increasing prevalence of uncommon fungal species and higher antifungal resistance has turned antifungal susceptibility testing into an important monitoring tool. In response, we evaluated the activity of isavuconazole against 522 clinical mold isolates collected worldwide in 2017–2018, including 436 Aspergillus spp. isolates and 86 non- Aspergillus molds. The MIC values using Clinical and Laboratory Standards Institute methods for isavuconazole versus Aspergillus ranged from 0.015 mg/L to >8 mg/L. Isavuconazole showed comparable activity to itraconazole, posaconazole, and voriconazole against A. fumigatus species complex. Most of the Aspergillus spp. isolates tested (>90%) were wild type to all azoles and echinocandins. Eleven isolates were non–wild type to isavuconazole and the other 3 azoles, and 10 of those isolates were from Europe. The azoles and echinocandins showed poor activity against Fusarium and Scedosporium spp. Isavuconazole exhibited excellent activity against most species of Aspergillus and was comparable to itraconazole, posaconazole, and voriconazole against the less common molds. [ABSTRACT FROM AUTHOR]

Background: Sterol demethylation inhibitors (DMIs) have been widely used to manage agronomically important fungal diseases in wheat, but reports of DMI-resistant pathogens continue to mount. Parastagonospora nodorum shows a wide range of sensitivity to DMIs, but until now no molecular mechanisms have been identified to explain these differences. The aim of this study was to correlate the DMI sensitivity of a global collection of P. nodorum isolates with mutations in the CYP51 gene that encodes the target of DMI fungicides., Results: Two non-synonymous mutations connected to DMI resistance in other plant pathogenic fungi were detected for the first time in the CYP51 gene of P. nodorum. The two mutations occurred at amino acid position 144, which is homologous to position 137 in other pathogens. The Y144F mutation was detected in China, Denmark, Sweden and Switzerland while the Y144H mutation was found in China and Switzerland. Both mutations were correlated with significantly reduced sensitivity to the DMI fungicide propiconazole., Conclusion: CYP51 mutations conferred reduced sensitivity against DMIs in field populations of P. nodorum originating from China, Denmark, Sweden and Switzerland. © 2016 Society of Chemical Industry., (© 2016 Society of Chemical Industry.)