ROS production during symbiotic infection suppresses pathogenesis-related gene expression.
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ABSTRACT:
SUBMITTER: Peleg-Grossman S
PROVIDER: S-EPMC3443923 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Epichloë festucae is an endophytic fungus which systemically colonizes temperate grasses to establish symbiotic associations. Maintaining symptomless infection is a key requirement for endophytes, a feature that distinguishes them from pathogenic fungi. While pathogenic fungi extend their hyphae by tip growth, hyphae of E. festucae systemically colonize the intercellular space of expanding host leaves via a unique mechanism of hyphal intercalary growth. This study reports that two homologous Rho GTPases, Cdc42 and RacA, have distinctive roles in the regulation of E. festucae growth in planta. Here we highlight the vital role of Cdc42 for intercalary hyphal growth, as well as involvement of RacA in regulation of hyphal network formation, and demonstrate the consequences of mutations in these genes on plant tissue infection. Functions of Cdc42 and RacA are mediated via interactions with BemA and NoxR respectively, which are expected components of the ROS producing NOX complex. Symbiotic defects found in the racA mutant were rescued by introduction of a Cdc42 with key amino acids substitutions crucial for RacA function, highlighting the significance of the specific interactions of these GTPases with BemA and NoxR for their functional differentiation in symbiotic infection.
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Project description:Pathogenesis-related proteins (PR proteins) play crucial roles in the plant defense system. A novel PRP gene was isolated from highly resistant soybean infected with Phytophthora sojae (P. sojae) and was named GmPRP (GenBank accession number: KM506762). The amino acid sequences of GmPRP showed identities of 74%, 73%, 72% and 69% with PRP proteins from Vitis vinifera, Populus trichocarpa, Citrus sinensis and Theobroma cacao, respectively. Quantitative real-time reverse transcription PCR (qRT-PCR) data showed that the expression of GmPRP was highest in roots, followed by the stems and leaves. GmPRP expression was upregulated in soybean leaves infected with P. sojae. Similarly, GmPRP expression also responded to defense/stress signaling molecules, including salicylic acid (SA), ethylene (ET), abscisic acid (ABA) and jasmonic acid (JA). GmPRP was localized in the cell plasma membrane and cytoplasm. Recombinant GmPRP protein exhibited ribonuclease activity and significant inhibition of hyphal growth of P. sojae 1 in vitro. Overexpression of the GmPRP gene in T2 transgenic tobacco and T2 soybean plants resulted in enhanced resistance to Phytophthora nicotianae (P. nicotianae) and P. sojae race 1, respectively. These results indicated that the GmPRP protein played an important role in the defense of soybean against P. sojae infection.
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Project description:Background: Preeclampsia (PE) is one of the leading causes of maternal and fetal morbidity and mortality worldwide. Placental oxidative stress has been identified as a major pathway to the development of PE. Ferroptosis is a new form of regulated cell death that is associated with iron metabolism and oxidative stress, and likely mediates PE pathogenesis. The aim of the study was to identify the key molecules involved in ferroptosis to further explore the mechanism of ferroptosis in PE. Methods: Gene expression data and clinical information were downloaded from the GEO database. The limma R package was used to screen differentially expressed genes (DEGs) and intersected with ferroptosis genes. The GO and KEGG pathways were then analyzed. Next, hub genes were identified via weighted gene co-expression network analysis (WGCNA). Receiver operating curves (ROCs) were performed for diagnostic and Pearson's correlation of hub genes and clinicopathological characteristics. Immunohistochemistry and Western blot analysis were used to verify the expression of hub genes. Results: A total of 3,142 DEGs were identified and 30 ferroptosis-related DEGs were obtained. In addition, ferroptosis-related pathways were enriched by GO and KEGG using DEGs. Two critical modules and six hub genes that were highly related to diagnosis of PE were identified through WGCNA. The analysis of the clinicopathological features showed that NQO1 and SRXN1 were closely correlated with PE characteristics and diagnosis. Finally, Western blot and immunohistochemistry analysis confirmed that the expression of the SRXN1 protein in the placental tissue of patients with PE was significantly elevated, while the expression of NQO1 was significantly decreased. Conclusions: SRXN1 and NQO1 may be key ferroptosis-related proteins in the pathogenesis of PE. The study may provide a theoretical and experimental basis for revealing the pathogenesis of PE and improving the diagnosis of PE.
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Project description:BackgroundParasitic infections can increase susceptibility to bacterial co-infections. This may be true for urogenital schistosomiasis and bacterial urinary tract co-infections (UTI). We previously reported that this co-infection is facilitated by S. haematobium eggs triggering interleukin-4 (IL-4) production and sought to dissect the underlying mechanisms. The interleukin-4-inducing principle from Schistosoma mansoni eggs (IPSE) is one of the most abundant schistosome egg-secreted proteins and binds to IgE on the surface of basophils and mast cells to trigger IL-4 release. IPSE can also translocate into host nuclei using a nuclear localization sequence (NLS) to modulate host transcription. We hypothesized that IPSE is the factor responsible for the ability of S. haematobium eggs to worsen UTI pathogenesis.MethodsMice were intravenously administered a single 25 μg dose of recombinant S. haematobium-derived IPSE, an NLS mutant of IPSE or PBS. Following IPSE exposure, mice were serially weighed and organs analyzed by histology to assess for toxicity. Twenty-four hours after IPSE administration, mice were challenged with the uropathogenic E. coli strain UTI89 by urethral catheterization. Bacterial CFU were measured using urine. Bladders were examined histologically for UTI-triggered pathogenesis and by PCR for antimicrobial peptide and pattern recognition receptor expression.ResultsUnexpectedly, IPSE administration did not result in significant differences in urine bacterial CFU. However, IPSE administration did lead to a significant reduction in UTI-induced bladder pathogenesis and the expression of anti-microbial peptides in the bladder. Despite the profound effect of IPSE on UTI-triggered bladder pathogenesis and anti-microbial peptide production, mice did not demonstrate systemic ill effects from IPSE exposure.ConclusionsOur data show that IPSE may play a major role in S. haematobium-associated urinary tract co-infection, albeit in an unexpected fashion. These findings also indicate that IPSE either works in concert with other IL-4-inducing factors to increase susceptibility of S. haematobium-infected hosts to bacterial co-infection or does not contribute to enhancing vulnerability to this co-infection.
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Project description:Aspergillus flavus is a soil-borne saprophyte and an opportunistic pathogen of both humans and plants. This fungus not only causes disease in important food and feed crops such as maize, peanut, cottonseed, and tree nuts but also produces the toxic and carcinogenic secondary metabolites (SMs) known as aflatoxins. Polyamines (PAs) are ubiquitous polycations that influence normal growth, development, and stress responses in living organisms and have been shown to play a significant role in fungal pathogenesis. Biosynthesis of spermidine (Spd) is critical for cell growth as it is required for hypusination-mediated activation of eukaryotic translation initiation factor 5A (eIF5A), and other biochemical functions. The tri-amine Spd is synthesized from the diamine putrescine (Put) by the enzyme spermidine synthase (Spds). Inactivation of spds resulted in a total loss of growth and sporulation in vitro which could be partially restored by addition of exogenous Spd. Complementation of the Δspds mutant with a wild type (WT) A. flavus spds gene restored the WT phenotype. In WT A. flavus, exogenous supply of Spd (in vitro) significantly increased the production of sclerotia and SMs. Infection of maize kernels with the Δspds mutant resulted in a significant reduction in fungal growth, sporulation, and aflatoxin production compared to controls. Quantitative PCR of Δspds mutant infected seeds showed down-regulation of aflatoxin biosynthetic genes in the mutant compared to WT A. flavus infected seeds. Expression analyses of PA metabolism/transport genes during A. flavus-maize interaction showed significant increase in the expression of arginine decarboxylase (Adc) and S-adenosylmethionine decarboxylase (Samdc) genes in the maize host and PA uptake transporters in the fungus. The results presented here demonstrate that Spd biosynthesis is critical for normal development and pathogenesis of A. flavus and pre-treatment of a Δspds mutant with Spd or Spd uptake from the host plant, are insufficient to restore WT levels of pathogenesis and aflatoxin production during seed infection. The data presented here suggest that future studies targeting spermidine biosynthesis in A. flavus, using RNA interference-based host-induced gene silencing approaches, may be an effective strategy to reduce aflatoxin contamination in maize and possibly in other susceptible crops.
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Project description:Alimentary oligofructose (OF) overload can induce several diseases in cattle, such as ruminal acidosis, laminitis, and synovitis. The role of blood polymorphonuclear neutrophil (PMN) remains unclear during OF overload. The aim of this study was to investigate the dynamic changes in reactive oxygen species (ROS) production and the expression profile of genes in blood PMN in a model of OF overload. Twelve clinically healthy and non-pregnant Chinese Holstein heifers, aged between 18 and 26 mo, weighing 335-403 kg, BCS (5-point scale) ranges 2.7-3.3 were used for the experiments. OF heifers (n = 6) received 17 g/kg of BW oligofructose dissolved in 2 L/100 kg of BW tap water and the CON heifers (n = 6) received 2 L/100 kg of BW tap water. Blood PMN was isolated for each heifer 0, 6, 12, 18, 24, 36, 48, 60, and 72 h after administration. PMN was analyzed either by endogenous and phorbol myristate acetate (PMA)-induced ROS production or by quantitative real-time PCR. After 12 h, PMA-induced ROS production decreased, which was sustained until 48 h. The expressions of inflammation markers (IL1α, IL1β, IL6, IL10, TNFα, STAT3, TLR4, MMP9, and HP) and eicosanoids (ALOX5, ALOX5AP, and PLA2G4A) were upregulated. The expression of adhesion and migration (CXCR2, CXCL8, CD62L, ITGA4, ITGAM, and ITGB2) in OF heifers was increased compared with CON heifers. The expression of oxidative stress (SOD2 and S100A8) was upregulated, while SOD1 and MPO were downregulated. In metabolism and receptor genes, the expressions of GRα and INSR decreased after 12 h, while Fas increased until 6 h and then decreased at 18 h. The expression of LDHA and PANX1 did not show any differences after OF overload. These findings indicate that OF overload induced systemic activation of PMN, which provides a step toward a better understanding of the role of innate immune responses in response to oral OF administration.
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