scholarly journals Redox, amino acid, and fatty acid metabolism intersect with bacterial virulence in the gut

2018 ◽  
Vol 115 (45) ◽  
pp. E10712-E10719 ◽  
Author(s):  
Reed Pifer ◽  
Regan M. Russell ◽  
Aman Kumar ◽  
Meredith M. Curtis ◽  
Vanessa Sperandio

The gut metabolic landscape is complex and is influenced by the microbiota, host physiology, and enteric pathogens. Pathogens have to exquisitely monitor the biogeography of the gastrointestinal tract to find a suitable niche for colonization. To dissect the important metabolic pathways that influence virulence of enterohemorrhagicEscherichia coli(EHEC), we conducted a high-throughput screen. We generated a dataset of regulatory pathways that control EHEC virulence expression under anaerobic conditions. This unraveled that the cysteine-responsive regulator, CutR, converges with the YhaO serine import pump and the fatty acid metabolism regulator FadR to optimally control virulence expression in EHEC. CutR activates expression of YhaO to increase activity of the YhaJ transcription factor that has been previously shown to directly activate the EHEC virulence genes. CutR enhances FadL, which is a pump for fatty acids that represses inhibition of virulence expression by FadR, unmasking a feedback mechanism responsive to metabolite fluctuations. Moreover, CutR and FadR also augment murine infection byCitrobacter rodentium, which is a murine pathogen extensively employed as a surrogate animal model for EHEC. This high-throughput approach proved to be a powerful tool to map the web of cellular circuits that allows an enteric pathogen to monitor the gut environment and adjust the levels of expression of its virulence repertoire toward successful infection of the host.

2020 ◽  
Author(s):  
Silu Wang ◽  
Madelyn J. Ore ◽  
Else K. Mikkelsen ◽  
Julie Lee-Yaw ◽  
Sievert Rohwer ◽  
...  

AbstractMitochondrial (mtDNA) and nuclear (nDNA) genes interact to govern metabolic pathways of mitochondria. When differentiated populations interbreed at secondary contact, incompatibilities between mtDNA of one population and nDNA of the other could result in low fitness of hybrids. Hermit Warblers (S. occidentalis abbreviated as HEWA) and inland Townsend’s Warblers (Setophaga townsendi, abbreviated as i-TOWA) exhibit distinct mtDNA haplotypes and a few nDNA regions of high differentiation, whereas coastal TOWA (c-TOWA) displays a mix of these genetic patterns consistent with ancient hybridization of HEWA and i-TOWA. Of the few highly-differentiated nDNA regions between i-TOWA and HEWA, two of these regions (on chromosome 5 and Z, respectively) are also differentiated between c-TOWA and i-TOWA, similar to the mtDNA pattern. These two nDNA regions are associated with mitochondrial fatty acid metabolism. Moreover, these nDNA regions are correlated with mtDNA ancestries among sites, a pattern consistent with mito-nuclear co-adaptation. Such mito-nuclear coevolution might be driven by climate-related selection, because the mito-nuclear ancestry is correlated with climatic conditions among sampling sites. These results suggest that cryptic differentiation in this species complex has been shaped by climate-correlated adaptation associated with mito-nuclear fatty acid metabolism.


2021 ◽  
Vol 11 ◽  
Author(s):  
Genghua Chen ◽  
Jiahui Chen ◽  
Jingwen Wu ◽  
Xueyi Ren ◽  
Limin Li ◽  
...  

Sex-linked dwarf (SLD) chicken, which is caused by a recessive mutation of the growth hormone receptor (GHR), has been widely used in the Chinese broiler industry. However, it has been found that the SLD chicken has more abdominal fat deposition than normal chicken. Excessive fat deposition not only reduced the carcass quality of the broilers but also reduced the immunity of broilers to diseases. To find out the key genes and the precise regulatory pathways that were involved in the GHR mutation-induced excessive fat deposition, we used high-fat diet (HFD) and normal diet to feed the SLD chicken and normal chicken and analyzed the differentially expressed genes (DEGs) among the four groups. Results showed that the SLD chicken had more abdominal fat deposition and larger adipocytes size than normal chicken and HFD can promote abdominal fat deposition and induce adipocyte hypertrophy. RNA sequencing results of the livers and abdominal fats from the above chickens revealed that many DEGs between the SLD and normal chickens were enriched in fat metabolic pathways, such as peroxisome proliferator-activated receptor (PPAR) signaling, extracellular matrix (ECM)-receptor pathway, and fatty acid metabolism. Importantly, by constructing and analyzing the GHR-downstream regulatory network, we found that suppressor of cytokine signaling 2 (SOCS2) and cytokine-inducible SH2-containing protein (CISH) may involve in the GHR mutation-induced abdominal fat deposition in chicken. The ectopic expression of SOCS2 and CISH in liver-related cell line leghorn strain M chicken hepatoma (LMH) cell and immortalized chicken preadipocytes (ICP) revealed that these two genes can regulate fatty acid metabolism, adipocyte differentiation, and lipid droplet accumulation. Notably, overexpression of SOCS2 and CISH can rescue the hyperactive lipid metabolism and excessive lipid droplet accumulation of primary liver cell and preadipocytes that were isolated from the SLD chicken. This study found some genes and pathways involved in abdominal fat deposition of the SLD chicken and reveals that SOCS2 and CISH are two key genes involved in the GHR mutation-induced excessive fat deposition of the SLD chicken.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Peng Zhang ◽  
Yuqiang Zhu ◽  
Shengjun Zhou

Abstract Background Cucumber (Cucumis sativus L.) is a widely planted vegetable crop that suffers from various pathogen infections. Powdery mildew (PM) is typical disease caused by Sphaerotheca fuliginea infection and destroys the production of cucumber. However, the metabolic responses to S. fuliginea infection are largely unknown. Results In our study, a PM resistant variety ‘BK2’ and a susceptible variety ‘H136’ were used to screen differentially accumulated metabolites (DAMs) and differentially expressed genes (DEGs) under S. fuliginea infection. Most of DEGs and DAMs were enriched in several primary and secondary metabolic pathways, including flavonoid, hormone, fatty acid and diterpenoid metabolisms. Our data showed that many flavonoid-related metabolites were significantly accumulated in BK2 rather than H136, suggesting an essential role of flavonoids in formation of resistant quality. Changes in expression of CYP73A, CYP81E1, CHS, F3H, HCT and F3’M genes provided a probable explanation for the differential accumulation of flavonoid-related metabolites. Interestingly, more hormone-related DEGs were detected in BK2 compared to H136, suggesting a violent response of hormone signaling pathways in the PM-resistant variety. The number of fatty acid metabolism-related DAMs in H136 was larger than that in BK2, indicating an active fatty acid metabolism in the PM-susceptible variety. Conclusions Many differentially expressed transcription factor genes were identified under S. fuliginea infection, providing some potential regulators for the improvement of PM resistance. PM resistance of cucumber was controlled by a complex network consisting of various hormonal and metabolic pathways.


1990 ◽  
Vol 29 (01) ◽  
pp. 28-34 ◽  
Author(s):  
F. C. Visser ◽  
M. J. van Eenige ◽  
G. Westera ◽  
J. P. Roos ◽  
C. M. B. Duwel

Changes in myocardial metabolism can be detected externally by registration of time-activity curves after administration of radioiodinated fatty acids. In this scintigraphic study the influence of lactate on fatty acid metabolism was investigated in the normal human myocardium, traced with 123l-17-iodoheptadecanoic acid (123l-17-HDA). In patients (paired, n = 7) lactate loading decreased the uptake of 123l-17-HDA significantly from 27 (control: 22-36) to 20 counts/min/pixel (16-31; p <0.05 Wilcoxon). The half-time value increased to more than 60 rriin (n = 5), oxidation decreased from 61 to 42%. Coronary vasodilatation, a well-known side effect of lactate loading, was studied separately in a dipyridamole study (paired, n = 6). Coronary vasodilatation did not influence the parameters of the time-activity curve. These results suggest that changes in plasma lactate level as occurring, among other effects, during exercise will influence the parameters of dynamic 123l-17-HDA scintigraphy of the heart.


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