scholarly journals Two Nimrod receptors, NimC1 and Eater, synergistically contribute to bacterial phagocytosis in Drosophila melanogaster

2018 ◽  
Author(s):  
Claudia Melcarne ◽  
Elodie Ramond ◽  
Jan Dudzic ◽  
Andrew J Bretscher ◽  
Éva Kurucz ◽  
...  
Keyword(s):  
Blood Cells ◽  
Ex Vivo ◽  
Gram Negative Bacteria ◽  
Null Mutant ◽  
Transmembrane Receptors ◽  
Gram Negative ◽  
Latex Beads ◽  
Cellular Immune

AbstractEater and NimC1 are transmembrane receptors of the Drosophila Nimrod family, specifically expressed in hemocytes, the insect blood cells. Previous ex vivo and in vivo RNAi studies have pointed to their role in the phagocytosis of bacteria. Here, we have created a novel null mutant in NimC1 to re-evaluate the role of NimC1, alone or in combination with Eater, in the cellular immune response. We show that NimC1 functions as an adhesion molecule ex vivo, but in contrast to Eater is not required for hemocyte sessility in vivo. Ex vivo phagocytosis assays and electron microscopy experiments confirmed that Eater is the main phagocytic receptor for Gram-positive, but not Gram-negative bacteria, and contributes to microbe tethering to hemocytes. Surprisingly, the NimC1 deletion did not impair phagocytosis of bacteria, nor their adhesion to the hemocytes. However, phagocytosis of both types of bacteria was almost abolished in NimC11;eater1 hemocytes. This indicates that both receptors contribute synergistically to the phagocytosis of bacteria, but that Eater can bypass the requirement for NimC1. Finally, we uncovered that NimC1, but not Eater, is essential for uptake of latex beads and zymosan particles. We conclude that Eater and NimC1 are the two main receptors for phagocytosis of bacteria in Drosophila, and that each receptor likely plays distinct roles in microbial uptake.

scholarly journals Thymosin alpha 1 mitigates cytokine storm in blood cells from COVID-19 patients

2020 ◽  
Author(s):  
Claudia Matteucci ◽  
Antonella Minutolo ◽  
Emanuela Balestrieri ◽  
Vita Petrone ◽  
Marialaura Fanelli ◽  
...  
Keyword(s):  
Immune System ◽  
Blood Cells ◽  
Ex Vivo ◽  
Cell Subset ◽  
Adverse Outcomes ◽  
Cytokine Signaling ◽  
Cytokine Storm ◽  
Thymosin Alpha 1

Abstract COVID-19 is characterized by immune-mediated lung injury and complex alterations of the immune system, such as lymphopenia and cytokine storm, that have been associated with adverse outcomes underlining a fundamental role of host response in SARS-CoV-2 infection and the pathogenesis of the disease. Thymosin alpha 1 (Tα1) is one of the molecules used in the management of COVID-19, since it is known to restore the homeostasis of the immune system during infections and cancer. Here we captured the interconnected biological processes regulated by Tα1 in CD8+ T cells under inflammatory conditions. Genes associated with cytokine signaling and production were found up-regulated in blood cells from COVID-19 patients and the ex-vivo treatment with Tα1 mitigated cytokines expression and inhibited lymphocytes activation in CD8+ T cell subset specifically, suggesting the potential role of Tα1 in modulating the immune response homeostasis and the cytokine storm in vivo.

scholarly journals Resistance to antibiotics in Gram-negative bacteria isolated from broiler carcasses

2002 ◽  
Vol 54 (1) ◽  
pp. 1-7
Author(s):  
M.A.S. Moreira ◽  
C.A. Moraes
Keyword(s):  
Antibiotic Resistance ◽  
Resistant Bacteria ◽  
Processing Plant ◽  
Growth Promoter ◽  
Gram Negative Bacteria ◽  
Beta Lactams ◽  
Gram Negative ◽  
Low Levels

One hundred and ninety-seven isolates of Gram-negative bacteria, comprising 10 genera, were isolated from poultry carcasses at a processing plant in order to investigate resistance to low levels of antibiotics. The samples were taken just after evisceration and before inspection. Most of the isolates were of Samonella and Escherichia. Other genera present were Enterobacter, Serratia, Klebsiella, Kluyvera, Erwinia, Citrobacter, Pseudomonas and Aeromonas. Distinct profiles of antibiotic resistance were detected. Resistance to more than two antibiotics predominated and spanned several classes of antibiotics. Salmonellae and escherichiae were mainly resistant to the aminoglycosides, followed by tetracycline, nitrofuran, sulpha, macrolide, chloramphenicol, quinolones and beta-lactams. Most isolates were sensitive to 30mug/ml olaquindox, the growth promoter in use at the time of sampling. However, many were resistant to a level of 10mug/ml and 13mug/ml olaquindox, levels present in the gut due to the dilution in the feed. The results suggest a possible role of low level administration of antibiotics to broilers in selecting multi-resistant bacteria in vivo.

The role of complement and CD14 in the Gram-negative bacteria induced inflammatory reaction: In vitro evidence and design of an in vivo porcine model

2007 ◽  
Vol 44 (1-3) ◽  
pp. 182
Author(s):  
Bernt Christian Hellerud ◽  
Ebbe B. Thorgersen ◽  
Albert Castellheim ◽  
Erik W. Nielsen ◽  
Anne Pharo ◽  
...  
Keyword(s):  
Inflammatory Reaction ◽  
Porcine Model ◽  
Gram Negative Bacteria ◽  
Gram Negative

Relationship between Adaptive Changing of Lysophosphatidylethanolamine Content in the Bacterial Envelope and Ampicillin Sensitivity of Yersinia pseudotuberculosis

2018 ◽  
Vol 28 (5) ◽  
pp. 236-239
Author(s):  
Nina Sanina ◽  
Lyudmila Pomazenkova ◽  
Svetlana Bakholdina ◽  
Natalia Chopenko ◽  
Anna Zabolotnaya ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Culture Medium ◽  
Bacterial Resistance ◽  
Yersinia Pseudotuberculosis ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Control Value ◽  
And Function

The low permeability of porin channels is the possible reason for Gram-negative bacterial resistance to antibiotics. The adaptive accumulation of lysophosphatidylethanolamine (LPE) in <i>Yersinia pseudotuberculosis</i> induces conformational changes of OmpF porin that may hinder the transport of antibiotics through this channel. The present study was aimed to test whether the changes in LPE content affect the resistance of bacteria to ampicillin. The addition of glucose to the culture medium was shown to simultaneously increase the level of LPE and minimum inhibitory concentration (MIC) for ampicillin of <i>Y. pseudotuberculosis</i> cells 6- and 2-fold, respectively. However, the coadministration of glucose and polyphenol extract from buckwheat husks reduced the content of LPE 2-fold and restored MIC to the control value. Thus, PBEH can be used as antibiotic adjuvant to improve an antibiotic’s ability to cross the outer membrane. The present work demonstrated: (i) the role of adaptive changes in the lipid composition of <i>Y. pseudotuberculosis</i> in<i></i> the development of antibiotic resistance, and (ii) the promising use of PBEH in combination therapy to increase the susceptibility of Gram-negative bacteria to the conventional β-lactam antibiotics, probably attenuating in vivo a previously demonstrated effect of LPE on the conformation and function of the OmpF channel.

scholarly journals Physiological role of the previously unexplained benzenetriol dioxygenase homolog in the Burkholderia sp. strain SJ98 4-nitrophenol catabolic pathway

2021 ◽  
Author(s):  
Juan Liu ◽  
Ying Xu ◽  
Shi-Kai Deng ◽  
Lei Liu ◽  
Jun Min ◽  
...  
Keyword(s):  
Industrial Revolution ◽  
Physiological Role ◽  
Nitroaromatic Compounds ◽  
Gram Negative Bacteria ◽  
Natural Ecosystems ◽  
Gram Negative ◽  
Benzenetriol Dioxygenase ◽  
Nitrophenol Degradation

4-Nitrophenol, a priority pollutant, is degraded by Gram-positive and Gram-negative bacteria, via 1,2,4-benzenetriol (BT) and hydroquinone (HQ), respectively. All enzymes involved in the two pathways have been functionally identified. So far, all Gram-negative 4-nitrophenol utilizers are from genera Pseudomonas and Burkholderia. But it remains a mystery why pnpG, an apparently superfluous BT 1,2-dioxygenase encoding gene, always coexists in the catabolic cluster (pnpABCDEF) encoding 4-nitrophenol degradation via HQ. Here, the physiological role of pnpG in Burkholderia sp. strain SJ98 was investigated. Deletion and complementation experiments established that pnpG is essential for strain SJ98 growing on 4-nitrocatechol rather than 4-nitrophenol. During 4-nitrophenol degradation by strain SJ98 and its two variants (pnpG deletion and complementation strains), 1,4-benzoquinone and HQ were detected, but neither 4-nitrocatechol nor BT was observed. When the above three strains (the wild-type and complementation strains with 2,2’-dipyridyl) were incubated with 4-nitrocatechol, BT was the only intermediate detected. The results established the physiological role of pnpG that encodes BT degradation in vivo. Biotransformation analyses showed that the pnpA-deleted strain was unable to degrade both 4-nitrophenol and 4-nitrocatechol. Thus the previously characterized 4-nitrophenol monooxygenase PnpASJ98 is also essential for the conversion of 4-nitrocatechol to BT. Among 775 available genomes in Pseudomonas and Burkholderia, as many as 89 genomes were found to contain putative pnpBCDEFG. The paucity of pnpA (3 in 775 genomes) implies that the extension of BT and HQ pathways enabling degradation of 4-nitrophenol and 4-nitrocatechol is more rare and recent, and likely due to the release of xenobiotic nitroaromatic compounds. IMPORTANCE An apparently superfluous gene (pnpG) encoding BT 1,2-dioxygenase is always found in the catabolic clusters involved in 4-nitrophenol degradation via HQ by Gram-negative bacteria. Our experiments reveal that pnpG is not essential for 4-nitrophenol degradation in Burkholderia sp. strain SJ98, but instead enables its degradation of 4-nitrocatechol via BT. The presence of pnpG genes broadens the range of growth substrates to include 4-nitrocatechol or BT, intermediates from microbial degradation of many aromatic compounds in natural ecosystems. In addition, the existence of pnpCDEFG in 11.6% of the aforementioned two genera suggests that the ability to degrade BT and HQ simultaneously is ancient. The extension of BT and HQ pathways including 4-nitrophenol degradation seems to be an adaptive evolution for responding to synthetic nitroaromatic compounds entering the environment since the industrial revolution.

The Role of Polyphenols in the Modulation of Plasma Non-Enzymatic Antioxidant Capacity (NEAC)

2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito
Keyword(s):  
Antioxidant Capacity ◽  
Dietary Intervention ◽  
Ex Vivo ◽  
The Body ◽  
Dietary Polyphenols ◽  
Enzymatic Antioxidant ◽  
Endogenous Antioxidant

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.

scholarly journals The antimicrobial potential of cannabidiol

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Mark A. T. Blaskovich ◽  
Angela M. Kavanagh ◽  
Alysha G. Elliott ◽  
Bing Zhang ◽  
Soumya Ramu ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Modern Medicine ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
New Class ◽  
Clostridioides Difficile ◽  
Excellent Activity ◽  
Induce Resistance ◽  
First Time

AbstractAntimicrobial resistance threatens the viability of modern medicine, which is largely dependent on the successful prevention and treatment of bacterial infections. Unfortunately, there are few new therapeutics in the clinical pipeline, particularly for Gram-negative bacteria. We now present a detailed evaluation of the antimicrobial activity of cannabidiol, the main non-psychoactive component of cannabis. We confirm previous reports of Gram-positive activity and expand the breadth of pathogens tested, including highly resistant Staphylococcus aureus, Streptococcus pneumoniae, and Clostridioides difficile. Our results demonstrate that cannabidiol has excellent activity against biofilms, little propensity to induce resistance, and topical in vivo efficacy. Multiple mode-of-action studies point to membrane disruption as cannabidiol’s primary mechanism. More importantly, we now report for the first time that cannabidiol can selectively kill a subset of Gram-negative bacteria that includes the ‘urgent threat’ pathogen Neisseria gonorrhoeae. Structure-activity relationship studies demonstrate the potential to advance cannabidiol analogs as a much-needed new class of antibiotics.

scholarly journals Animal Models in the Evaluation of the Effectiveness of Phage Therapy for Infections Caused by Gram-Negative Bacteria from the ESKAPE Group and the Reliability of Its Use in Humans

2021 ◽  
Vol 9 (2) ◽  
pp. 206
Author(s):  
Martyna Cieślik ◽  
Natalia Bagińska ◽  
Andrzej Górski ◽  
Ewa Jończyk-Matysiak
Keyword(s):  
Animal Models ◽  
Phage Therapy ◽  
Animal Experiments ◽  
Species Group ◽  
Effectiveness Evaluation ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Enterobacter Species ◽  
The Individual

The authors emphasize how extremely important it is to highlight the role played by animal models in an attempt to determine possible phage interactions with the organism into which it was introduced as well as to determine the safety and effectiveness of phage therapy in vivo taking into account the individual conditions of a given organism and its physiology. Animal models in which phages are used make it possible, among other things, to evaluate the effective therapeutic dose and to choose the possible route of phage administration depending on the type of infection developed. These results cannot be applied in detail to the human body, but the knowledge gained from animal experiments is invaluable and very helpful. We would like to highlight how useful animal models may be for the possible effectiveness evaluation of phage therapy in the case of infections caused by gram-negative bacteria from the ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species) group of pathogens. In this review, we focus specifically on the data from the last few years.

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