The Fungal CYP51s: Their Functions, Structures, Related Drug Resistance, and Inhibitors

Zhang, Jingxiang; Li, Liping; Lv, Quan-Zhen; Yan, Lan; Wang, Yan; Jiang, Yuanying

doi:10.3389/fmicb.2019.00691

Cited by 133 publications

(96 citation statements)

References 184 publications

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Section: Other Genes In Pd Pathogenicitymentioning

confidence: 99%

“…Fungal CYP51s belong to the cytochrome P450 monooxygenase (CYP) superfamily and are essential for ergosterol synthesis in fungal membranes [96]. Fungal CYP51s, such as PdCYP51A and PdCYP51B from Pd, are known for their involvement in resistance to fungicides inhibiting ergosterol synthesis, but increasing evidence shows that some of them also play a role in fungal growth and virulence [96]. A recent study showed that overexpression of PdCYP51B increased Pd virulence on citrus fruit compared with the wild type strain, indicating that PdCYP51B contributes to Pd pathogenicity possibly by regulating ergosterol synthesis in Pd membranes [97].…”

Section: Other Genes In Pd Pathogenicitymentioning

confidence: 99%

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Citrus Postharvest Green Mold: Recent Advances in Fungal Pathogenicity and Fruit Resistance

et al. 2020

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As the major postharvest disease of citrus fruit, postharvest green mold is caused by the necrotrophic fungus Penicillium digitatum (Pd), which leads to huge economic losses worldwide. Fungicides are still the main method currently used to control postharvest green mold in citrus fruit storage. Investigating molecular mechanisms of plant–pathogen interactions, including pathogenicity and plant resistance, is crucial for developing novel and safer strategies for effectively controlling plant diseases. Despite fruit–pathogen interactions remaining relatively unexplored compared with well-studied leaf–pathogen interactions, progress has occurred in the citrus fruit–Pd interaction in recent years, mainly due to their genome sequencing and establishment or optimization of their genetic transformation systems. Recent advances in Pd pathogenicity on citrus fruit and fruit resistance against Pd infection are summarized in this review.

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Section: Other Genes In Pd Pathogenicitymentioning

confidence: 99%

Section: Other Genes In Pd Pathogenicitymentioning

confidence: 99%

Citrus Postharvest Green Mold: Recent Advances in Fungal Pathogenicity and Fruit Resistance

et al. 2020

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“…PQS could also be found within key genes linked to virulence and drug resistance in these fungi. In A. fumigatus, PQS could be found in cyp51A, cyp51B, atrF, and fsk1 (involved in resistance to azoles and echinocandins) [60][61][62], laeA, gliN and gliP, (involved in toxin and metabolite biosynthesis) [63,64], pksP, arp2, abr1, arb2, and ayg1 (involved in the production of the virulence factor DHN-melanin) [65], in addition to numerous important transcription factors (meaB, hapX, pacC) [66]. Similarly, in C. neoformans, PQS could be found in genes linked to azole resistance (afr1) [67], melanin production (lac2) [68], and transcription factors (pacC/rim101).…”

Section: Genes In a Fumigatus That Are Upregulated During Fungal Germentioning

confidence: 99%

Cross kingdom analysis of putative quadruplex-forming sequences in fungal genomes: novel antifungal targets to ameliorate fungal pathogenicity?

Warner

Bohálová

Brázda

et al. 2020

Preprint

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Fungi contribute to upwards of 1.5 million human deaths annually, are involved in the spoilage of up to a third of food crops, and have a devastating effect on plant and animal biodiversity. Moreover, this already significant issue is exacerbated by a rise in antifungal resistance and a critical requirement for novel drug targets. Quadruplexes are four-stranded secondary structures in nucleic acids which can regulate processes such as transcription, translation, replication, and recombination. They are also found in genes linked to virulence in microbes, and quadruplex-binding ligands have been demonstrated to eliminate drug resistant pathogens. Using a computational approach, we identified putative quadruplex-forming sequences (PQS) in 1362 genomes across the fungal kingdom and explored their potential involvement in virulence, drug resistance, and pathogenicity. Here we present the largest analysis of PQS in fungi and identified significant heterogeneity of these sequences throughout phyla, genera, and species. Moreover, PQS were genetically conserved. Notably, loss of PQS in cryptococci and aspergilli was associated with pathogenicity. PQS in the clinically important pathogens Aspergillus fumigatus, Cryptococcus neoformans, and Candida albicans were located within genes (particularly coding regions), mRNA, repeat regions, mobile elements, tRNA, ncRNA, rRNA, and the centromere. Genes containing PQS in these organisms were found to be primarily associated with metabolism, nucleic acid binding, transporter activity, and protein modification. Finally, PQS were found in over 100 genes associated with virulence, drug resistance, or key biological processes in these pathogenic fungi and were found in genes which were highly upregulated during germination, hypoxia, oxidative stress, iron limitation, and in biofilms. Taken together, quadruplexes in fungi could present interesting novel targets to ameliorate fungal virulence and overcome drug resistance.

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“…Being involved in the sterol metabolism (16,17), the hemoprotein CYP51 is considered to be essential and, therefore, a promising drug target against different trypanosomatids (18,19,20). Ketoconazole is one of the broadly used compounds which binds to the active site of CYP51 and inhibits its activity (21). The genome of T. brucei s.l.…”

Section: Endogenous Hemoproteins Activity Depends On Hphbrmentioning

confidence: 99%

Heme-deficient metabolism and impaired cellular differentiation as an evolutionary trade-off for human infectivity in Trypanosoma brucei gambiense

Horáková

Lecordier

Cunha

et al. 2020

Preprint

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Resistance to African trypanosomes in humans relies on targeting of a trypanosome lytic factor 1 (TLF1) to trypanosome haptoglobin-hemoglobin receptor (HpHbR). While TLF1 avoidance by the inactivation of the HpHbR contributes to Trypanosoma brucei gambiense human infectivity, the evolutionary trade-off of this adaptation is unknown. Both T. b. gambiense with inactive HpHbR, as well as a genetically engineered T.b.brucei HpHbR knock-out show only trace levels of intracellular heme and lack the downstream hemoprotein activities, thereby providing an extraordinary example of aerobic parasite proliferation in the absence of heme. We further show that HpHbR facilitates the developmental progression by inducing PAD-1 expression that is associated with the formation of cell cycle-arrested stumpy forms in T. b.brucei . Accordingly, T. b. gambiense was found to be poorly competent for slender-to-stumpy differentiation unless a functional HpHbR receptor derived from T. b. brucei was genetically restored.

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The Fungal CYP51s: Their Functions, Structures, Related Drug Resistance, and Inhibitors

Cited by 133 publications

References 184 publications

Citrus Postharvest Green Mold: Recent Advances in Fungal Pathogenicity and Fruit Resistance

Citrus Postharvest Green Mold: Recent Advances in Fungal Pathogenicity and Fruit Resistance

Cross kingdom analysis of putative quadruplex-forming sequences in fungal genomes: novel antifungal targets to ameliorate fungal pathogenicity?

Heme-deficient metabolism and impaired cellular differentiation as an evolutionary trade-off for human infectivity in Trypanosoma brucei gambiense

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