The methionine biosynthesis regulator AaMetR contributes to oxidative stress tolerance and virulence in Alternaria alternata

Gai, Yunpeng; Liu, Bing; Ma, Hongshen; Li, Lei; Chen, Xinglong; Moenga, Susan M.; Riely, Brendan K.; Fayyaz, Amna; Wang, Mingshuang; Li, Hongye

doi:10.1016/j.micres.2018.11.007

Cited by 41 publications

(44 citation statements)

References 50 publications

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“…fumigatus led to decrease virulence in both pathogens, which is consistent with previous literature published, in which C . neoformans met3Δ and met6Δ mutants are avirulent in animal model, reinforcing the idea that sulfur assimilation maybe an important feature for fungal pathogenesis 22,23,59,61,62 . Despite the clear connection among sulfur assimilation, sulfur amino acid biosynthesis, and virulence, very little is known about the interrelation of these biological processes and their regulatory mechanisms in C .…”

Section: Introductionsupporting

confidence: 54%

“…fumigatus deletion of metR ( CYS3 homologue) is essential for pulmonary aspergillosis dissemination, similar to our data in G . mellonella and previous work where a functional sulfur amino acid biosynthesis is important for virulence 22,23,59,74 . Likely, the inability to synthesize sulfur amino acids plays multiples roles on C .…”

Section: Discussionmentioning

confidence: 87%

“…In the plant pathogen A . alternate , methionine and cysteine deficiency led to increased sensitivity to H 2 O 2 , suggesting that these auxotrophs affect oxidative stress response 59 .…”

Section: Discussionmentioning

confidence: 99%

“…Elements of the sulfur regulatory pathway have been uncovered in Alternaria alternate , Aspergillus fumigatus , and Mycobacterium . The first is considered a plant pathogen and the last two, human pathogens 59–61 . The deletion of metR from A .…”

Section: Introductionmentioning

confidence: 99%

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The regulation of the sulfur amino acid biosynthetic pathway in Cryptococcus neoformans: the relationship of Cys3, Calcineurin, and Gpp2 phosphatases

Melo

Martho

Roberto

et al. 2019

Sci Rep

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Cryptococcosis is a fungal disease caused by C . neoformans . To adapt and survive in diverse ecological niches, including the animal host, this opportunistic pathogen relies on its ability to uptake nutrients, such as carbon, nitrogen, iron, phosphate, sulfur, and amino acids. Genetic circuits play a role in the response to environmental changes, modulating gene expression and adjusting the microbial metabolism to the nutrients available for the best energy usage and survival. We studied the sulfur amino acid biosynthesis and its implications on C . neoformans biology and virulence. CNAG_04798 encodes a BZip protein and was annotated as CYS3 , which has been considered an essential gene. However, we demonstrated that CYS3 is not essential, in fact, its knockout led to sulfur amino acids auxotroph. Western blots and fluorescence microscopy indicated that GFP-Cys3, which is expressed from a constitutive promoter, localizes to the nucleus in rich medium (YEPD); the addition of methionine and cysteine as sole nitrogen source (SD–N + Met/Cys) led to reduced nuclear localization and protein degradation. By proteomics, we identified and confirmed physical interaction among Gpp2, Cna1, Cnb1 and GFP-Cys3. Deletion of the calcineurin and GPP2 genes in a GFP-Cys3 background demonstrated that calcineurin is required to maintain Cys3 high protein levels in YEPD and that deletion of GPP2 causes GFP-Cys3 to persist in the presence of sulfur amino acids. Global transcriptional profile of mutant and wild type by RNAseq revealed that Cys3 controls all branches of the sulfur amino acid biosynthesis, and sulfur starvation leads to induction of several amino acid biosynthetic routes. In addition, we found that Cys3 is required for virulence in Galleria mellonella animal model.

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Section: Introductionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 87%

“…In the plant pathogen A . alternate , methionine and cysteine deficiency led to increased sensitivity to H 2 O 2 , suggesting that these auxotrophs affect oxidative stress response 59 .…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The regulation of the sulfur amino acid biosynthetic pathway in Cryptococcus neoformans: the relationship of Cys3, Calcineurin, and Gpp2 phosphatases

Melo

Martho

Roberto

et al. 2019

Sci Rep

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“…By contrast, MetR, a known TF involved in oxidative stress tolerance and pathogenicity 30 , displayed a head-to-head binding model (Fig. 2d ).…”

Section: Resultsmentioning

confidence: 98%

A compendium of DNA-binding specificities of transcription factors in Pseudomonas syringae

et al. 2020

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Pseudomonas syringae is a Gram-negative and model pathogenic bacterium that causes plant diseases worldwide. Here, we set out to identify binding motifs for all 301 annotated transcription factors (TFs) of P. syringae using HT-SELEX. We successfully identify binding motifs for 100 TFs. We map functional interactions between the TFs and their targets in virulence-associated pathways, and validate many of these interactions and functions using additional methods such as ChIP-seq, electrophoretic mobility shift assay (EMSA), RT-qPCR, and reporter assays. Our work identifies 25 virulence-associated master regulators, 14 of which had not been characterized as TFs before.

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Transcriptomic and metabolomic analyses provide evidence on the biocontrol mechanism responsible for the inhibition of Botrytis cinerea and Alternaria alternata by Bacillus velezensis in kiwifruit

Zeng,

Li,

Leng

et al. 2024

Food Frontiers

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Botrytis cinerea and Alternaria alternata are major pre‐ and postharvest plant pathogens of kiwifruit and responsible for significant economic losses. Although synthetic fungicides are the main source of controlling these pathogens, their use can lead to pathogen resistance, pollution of the environment, and their residues on agricultural produce can represent a health risk to humans. Bacillus velezensis is an ecofriendly bacterium with biocontrol potential. The objectives of the present study were to determine the efficacy of B. velezensis against B. cinerea and A. alternata, both of which are pre‐ and postharvest pathogens of kiwifruit, and investigate the mechanisms responsible for its biocontrol activity using transcriptomic and metabolomic methodology. Dual cultures of B. velezensis and either B. cinerea or A. alternata versus single cultures were used to conduct a transcriptomic and metabolomic analyses to provide insight into the mechanism by which B. velezensis inhibits B. cinerea and A. alternata. A total of 2499 and 3248 differentially expressed genes (DEGs) were identified in the B. velezensis/B. cinerea and B. velezensis/A. alternata comparisons, respectively. Genes related to sporulation, virulence, and hydrolase activity were downregulated in B. cinerea and A. alternata. Genes associated with MAPK signaling and the TCA cycle were also downregulated. Our study provides new insights into mechanism underlying the inhibition of B. cinerea and A. alternata by B. velezensis. Our results also demonstrate the potential of B. velezensis as a biocontrol agent against these two major pathogens of kiwifruit.

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The methionine biosynthesis regulator AaMetR contributes to oxidative stress tolerance and virulence in Alternaria alternata

Cited by 41 publications

References 50 publications

The regulation of the sulfur amino acid biosynthetic pathway in Cryptococcus neoformans: the relationship of Cys3, Calcineurin, and Gpp2 phosphatases

The regulation of the sulfur amino acid biosynthetic pathway in Cryptococcus neoformans: the relationship of Cys3, Calcineurin, and Gpp2 phosphatases

A compendium of DNA-binding specificities of transcription factors in Pseudomonas syringae

Transcriptomic and metabolomic analyses provide evidence on the biocontrol mechanism responsible for the inhibition of Botrytis cinerea and Alternaria alternata by Bacillus velezensis in kiwifruit

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