Probing Bacterial-Toxin Inhibition with Synthetic Glycopolymers Prepared by Tandem Post-Polymerization Modification: Role of Linker Length and Carbohydrate Density

Bacteria inhabit diverse environmental niches and consequently must modulate their metabolism to adapt to stress. The nucleotide second messengers guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate (pppGpp) (collectively referred to as (p)ppGpp) are essential for survival during nutrient starvation. (p)ppGpp is synthesized by the RelA-SpoT homologue (RSH) protein family and coordinates the control of cellular metabolism through its combined effect on over 50 proteins. While the role of (p)ppGpp has largely been associated with nutrient limitation, recent studies have shown that (p)ppGpp and related nucleotides have a previously underappreciated effect on different aspects of bacterial physiology, such as maintaining cellular homeostasis and regulating bacterial interactions with a host, other bacteria, or phages. (p)ppGpp produced by pathogenic bacteria facilitates the evasion of host defenses such as reactive nitrogen intermediates, acidic pH, and the complement system. Additionally, (p)ppGpp and pyrophosphorylated derivatives of canonical adenosine nucleotides called (p)ppApp are emerging as effectors of bacterial toxin proteins. Here, we review the RSH protein family with a focus on its unconventional roles during host infection and bacterial competition.

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Haemolytic activity and cellular toxicity of SBA-15-type silicas: elucidating the role of the mesostructure, surface functionality and linker length

Journal of Materials Chemistry B ◽

10.1039/c4tb01901f ◽

2015 ◽

Vol 3 (13) ◽

pp. 2714-2724 ◽

Cited By ~ 13

Author(s):

Małgorzata Ferenc ◽

Nadia Katir ◽

Katarzyna Miłowska ◽

Mosto Bousmina ◽

Jean-Pierre Majoral ◽

...

Keyword(s):

Haemolytic Activity ◽

Cellular Toxicity ◽

Linker Length ◽

Surface Functionality

Haemolytic activity and cellular toxicity of native, amino-, mercapto-, and carboxy-terminated SBA-15-type silicates were investigated.

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Melatonin restores Muc2 depletion induced by V. vulnificus VvpM via melatonin receptor 2 coupling with Gαq

Journal of Biomedical Science ◽

10.1186/s12929-019-0606-x ◽

2020 ◽

Vol 27 (1) ◽

Cited By ~ 1

Author(s):

Young-Min Lee ◽

Jong Pil Park ◽

Young Hyun Jung ◽

Hyun Jik Lee ◽

Jun Sung Kim ◽

...

Keyword(s):

Recombinant Protein ◽

Mouse Models ◽

Functional Role ◽

Bacterial Toxin ◽

Intestinal Epithelial ◽

Melatonin Receptor ◽

Intestinal Mucin ◽

Infection Treatment ◽

Regulatory Effects

Abstract Background Melatonin (5-methoxy-N-acetyltryptamine), a hormone produced in the pineal gland, has a variety of biological functions as an antioxidant, but a functional role of melatonin in the regulation of intestinal mucin (Muc) production during bacterial infection has yet to be described in detail. In this study, we investigate the effects of melatonin during Muc2 repression elicited by the Gram-negative bacterium V. vulnificus. Methods Mucus-secreting human HT29-MTX cells were used to study the functional role of melatonin during Muc2 depletion induced by the recombinant protein (r) VvpM produced by V. vulnificus. The regulatory effects of melatonin coupling with melatonin receptor 2 (MT2) on the production of reactive oxygen species (ROS), the activation of PKCδ and ERK, and the hypermethylation of the Muc2 promoter as induced by rVvpM were examined. Experimental mouse models of V. vulnificus infection were used to study the role of melatonin and how it neutralizes the bacterial toxin activity related to Muc2 repression. Results Recombinant protein (r) VvpM significantly reduced the level of Muc2 in HT29-MTX cells. The repression of Muc2 induced by rVvpM was significantly restored upon a treatment with melatonin (1 μM), which had been inhibited by the knockdown of MT2 coupling with Gαq and the NADPH oxidase subunit p47 phox. Melatonin inhibited the ROS-mediated phosphorylation of PKCδ and ERK responsible for region-specific hypermethylation in the Muc2 promoter in rVvpM-treated HT29-MTX cells. In the mouse models of V. vulnificus infection, treatment with melatonin maintained the level of Muc2 expression in the intestine. In addition, the mutation of the VvpM gene from V. vulnificus exhibited an effect similar to that of melatonin. Conclusions These results demonstrate that melatonin acting on MT2 inhibits the hypermethylation of the Muc2 promoter to restore the level of Muc2 production in intestinal epithelial cells infected with V. vulnificus.

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Role of Linker Length and Antigen Density in Nanoparticle Peptide Vaccine

ACS Omega ◽

10.1021/acsomega.8b03391 ◽

2019 ◽

Vol 4 (3) ◽

pp. 5547-5555 ◽

Cited By ~ 4

Author(s):

Chintan H. Kapadia ◽

Shaomin Tian ◽

Jillian L. Perry ◽

J. Christopher Luft ◽

Joseph M. DeSimone

Keyword(s):

Peptide Vaccine ◽

Linker Length

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Somatostatin and muscarinic inhibition of canine enteric endocrine cells: cellular mechanisms

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1987.253.5.g684 ◽

1987 ◽

Vol 253 (5) ◽

pp. G684-G689

Author(s):

D. L. Barber ◽

M. Gregor ◽

A. H. Soll

Keyword(s):

Endocrine Cell ◽

Binding Protein ◽

Calcium Ionophore ◽

Bacterial Toxin ◽

Camp Accumulation ◽

Gtp Binding Protein ◽

Camp Content ◽

Gtp Binding ◽

Peptide Release

Using a recently developed canine primary enteric endocrine cell culture system, we have investigated the role of adenosine 3',5'-cyclic monophosphate (cAMP) in mediating the release of neurotensin and enteroglucagon. Epinephrine-stimulated peptide release was concomitant with an increase in cAMP accumulation. Carbachol and somatostatin (SRIF) markedly inhibited the epinephrine effect on both peptide release and cAMP content. The addition of 3-isobutyl-1-methylxanthine potentiated epinephrine-stimulated peptide release without altering the relative inhibition by carbachol and SRIF, suggesting that these agents did not inhibit endocrine cell function by increasing phosphodiesterase activity. To determine the role of cAMP production in mediating inhibition of peptide release, cells were incubated with the bacterial toxin, pertussis toxin (PT). In cultures pretreated with PT, carbachol inhibition of both peptide release and cAMP accumulation was completely reversed. In contrast, SRIF inhibition of cAMP content was completely reversed after PT treatment, but inhibition of peptide release was only partially reversed. Additionally, toxin treatment only partially reversed SRIF inhibition of forskolin- and calcium ionophore-stimulated peptide release. These data suggest that muscarinic cholinergic inhibition of neurotensin and enteroglucagon release is mediated entirely through the guanine nucleotide-binding protein (Ni) or a similar toxin-sensitive, GTP-binding protein. SRIF-inhibited peptide release is mediated partially through a toxin-sensitive substrate, as evidenced by PT reversal of reduced cAMP levels. SRIF may also inhibit neurotensin and enteroglucagon release by a cAMP-independent pathway that is not coupled to Ni or a similar PT-sensitive, GTP-binding protein.

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Insights on intermolecular FMN-heme domain interaction and the role of linker length in cytochrome P450cin fusion proteins

Biological Chemistry ◽

10.1515/hsz-2020-0134 ◽

2020 ◽

Vol 401 (11) ◽

pp. 1249-1255

Author(s):

Ketaki D. Belsare ◽

Anna Joëlle Ruff ◽

Ronny Martinez ◽

Ulrich Schwaneberg

Keyword(s):

Fusion Protein ◽

Enzyme System ◽

Cytochrome P450s ◽

Similar Amount ◽

Domain Interaction ◽

P450 Bm3 ◽

Linker Length ◽

Heme Domain

AbstractCytochrome P450s are an important group of enzymes catalyzing hydroxylation, and epoxidations reactions. In this work we describe the characterization of the CinA–CinC fusion enzyme system of a previously reported P450 using genetically fused heme (CinA) and FMN (CinC) enzyme domains from Citrobacter braaki. We observed that mixing individually inactivated heme (-) with FMN (-) domain in the CinA-10aa linker - CinC fusion constructs results in recovered activity and the formation of (2S)-2β-hydroxy,1,8-cineole (174 µM), a similar amount when compared to the fully functional fusion protein (176 µM). We also studied the effect of the fusion linker length in the activity complementation assay. Our results suggests an intermolecular interaction between heme and FMN parts from different CinA–CinC fusion protein similar to proposed mechanisms for P450 BM3 on the other hand, linker length plays a crucial influence on the activity of the fusion constructs. However, complementation assays show that inactive constructs with shorter linker lengths have functional subunits, and that the lack of activity might be due to incorrect interaction between fused enzymes.

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Bacteria in Carcinogenesis and Cancer Prevention: A Review Study

International Journal of Cancer Management ◽

10.5812/ijcm.107956 ◽

2021 ◽

Vol 14 (2) ◽

Author(s):

Negin Nokhandani ◽

Arash Poursheikhani ◽

Mahdyieh Naghavi Alhosseini ◽

Homa Davoodi

Keyword(s):

Cancer Therapy ◽

Cancer Prevention ◽

Tumor Therapy ◽

Toxin Production ◽

Human Condition ◽

Alternative Methods ◽

Bacterial Toxin ◽

Different Origins ◽

Bacteriolytic Therapy

Context: Although conventional therapies improve the conditions of patients with cancer, adverse side effects, and resistance to different therapies have convinced scientists to use alternative methods to overcome these problems. One of the most promising research directions is the application of specific types of bacteria and their components to prevent and treat different cancers. Apart from the ability of bacteria to modulate immune responses, various particular properties such as toxin production and anaerobic lifestyle, have made them one of the potential candidates to help cancer therapy. Evidence Acquisition: In this review, the latest information on the role of bacteria in carcinogenesis and cancer prevention in PubMed, Google scholar, and Science Direct databases in 2020 were considered using a combination of keywords “bacteria”, “carcinogenesis”, “cancer” and “prevention”. Results: Bacteria-cancer interactions can be studied in 2 areas of bacteria and carcinogenesis and the other bacteria and cancer treatment or prevention. In this review, bacterial carcinogenicity has been mentioned with 3 main mechanisms: bacterial toxin, bacterial metabolites, and chronic inflammation caused by bacteria. Bacterial-mediated tumor therapy (BMTT) is briefly discussed in 8 mechanisms including tumor-targeting bacterial therapy, gene therapy and vectors, bacterial products, arginine metabolism, magnetotactic bacteria, combination bacteriolytic therapy (COBALT), immunomodulation of bacteria in cancer, and immune survival. Conclusions: The importance of bacteria in terms of diversity in their interaction with humans, as well as their components that can affect homeostasis and the immune system, has made them a powerful factor in describing the human condition in health and disease. These important elements can be used in the prevention and treatment of many complex diseases with different origins like cancer. The present study can provide an overview of the role of bacteria in cancer development or prevention and potential approaches for bacteria in cancer therapy.

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ER bodies are induced by Pseudomonas syringae and negatively regulate immunity

Molecular Plant-Microbe Interactions ◽

10.1094/mpmi-11-20-0330-sc ◽

2021 ◽

Author(s):

Jose Rufian ◽

James Elmore ◽

Eduardo R Bejarano ◽

Carmen R. Beuzón ◽

Gitta Coaker

Keyword(s):

Immune Responses ◽

Pseudomonas Syringae ◽

Bacterial Infections ◽

De Novo ◽

Cell Types ◽

Beet Armyworm ◽

Bacterial Toxin ◽

Main Components ◽

New Evidence

ER bodies are endoplasmic reticulum-derived organelles present in plants belonging to the Brassicales order. In Arabidopsis thaliana, ER bodies are ubiquitous in cotyledons and roots, and present only in certain cell types in rosette leaves. However, both wounding and jasmonic acid treatment induce the formation of ER bodies in leaves. Formation of this structure is dependent on the transcription factor NAI1. The main components of the ER bodies are β-glucosidases (BGLUs), enzymes that hydrolyze specialized compounds. In Arabidopsis, PYK10 (BGLU23) and BGLU18 are the most abundant ER body proteins. In this work, we found that ER bodies are downregulated as a consequence of the immune responses induced by bacterial flagellin perception. Arabidopsis mutants defective in ER body formation show enhanced responses upon flagellin perception and enhanced resistance to bacterial infections. Furthermore, the bacterial toxin coronatine induces the formation of de novo ER bodies in leaves and its virulence function is partially dependent on this structure. Finally, we show that performance of the polyphagous beet armyworm herbivore, Spodoptera exigua, increases in plants lacking ER bodies. Altogether, we provide new evidence for the role of the ER bodies in plant immune responses.

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