scholarly journals Innate Immune Response against Staphylococcus aureus Preincubated with Subinhibitory Concentration of trans-Anethole

2020 ◽  
Vol 21 (11) ◽  
pp. 4178
Author(s):  
Paweł Kwiatkowski ◽  
Bartosz Wojciuk ◽  
Iwona Wojciechowska-Koszko ◽  
Łukasz Łopusiewicz ◽  
Bartłomiej Grygorcewicz ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Culture Medium ◽  
Antioxidant Activities ◽  
Innate Immune ◽  
Major Constituent ◽  
Human Neutrophils ◽  
Cell Size Distribution ◽  
Functional Changes ◽  
Star Anise ◽  
Cell Components

The study aimed to analyze morphological and functional changes of Staphylococcus aureus cells due to trans-anethole (a terpenoid and the major constituent of fennel, anise, or star anise essential oils) exposition, and their consequences for human neutrophils phagocytic activity as well as IL-8 production (recognized as the major chemoattractant). The investigation included the evaluation of changes occurring in S. aureus cultures, i.e., staphyloxanthin production, antioxidant activities, cell size distribution, and cells composition as a result of incubation with trans-anethole. It was found that the presence of trans-anethole in the culture medium reduced the level of staphyloxanthin production, as well as decreased antioxidant activities. Furthermore, trans-anethole-treated cells were characterized by larger size and a tendency to diffuse in comparison to the non-treated cells. Several cell components, such as phospholipids and peptidoglycan, were found remarkably elevated in the cultures treated with trans-anethole. As a result of the aforementioned cellular changes, the bacteria were phagocytized by neutrophils more efficiently (ingestion and parameters associated with killing activity were at a higher level as compared to the control system). Additionally, IL-8 production was at a higher level for trans-anethole modified bacteria. Our results suggest that trans-anethole represents a promising measure in combating severe staphylococcal infections, which has an important translational potential for clinical applications.

scholarly journals Serine-Aspartate Repeat Protein D Increases Staphylococcus aureus Virulence and Survival in Blood

2016 ◽  
Vol 85 (1) ◽  
Author(s):  
Fatemeh Askarian ◽  
Satoshi Uchiyama ◽  
J. Andrés Valderrama ◽  
Clement Ajayi ◽  
Johanna U. E. Sollid ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Ex Vivo ◽  
Innate Immune ◽  
Human Neutrophils ◽  
Infection Model ◽  
Bacterial Survival ◽  
Bacterial Killing ◽  
Content Type ◽  
Repeat Protein

ABSTRACT Staphylococcus aureus expresses a panel of cell wall-anchored adhesins, including proteins belonging to the microbial surface components recognizing adhesive matrix molecule (MSCRAMM) family, exemplified by the serine-aspartate repeat protein D (SdrD), which serve key roles in colonization and infection. Deletion of sdrD from S. aureus subsp. aureus strain NCTC8325-4 attenuated bacterial survival in human whole blood ex vivo, which was associated with increased killing by human neutrophils. Remarkably, SdrD was able to inhibit innate immune-mediated bacterial killing independently of other S. aureus proteins, since addition of recombinant SdrD protein and heterologous expression of SdrD in Lactococcus lactis promoted bacterial survival in human blood. SdrD contributes to bacterial virulence in vivo, since fewer S. aureus subsp. aureus NCTC8325-4 ΔsdrD bacteria than bacteria of the parent strain were recovered from blood and several organs using a murine intravenous infection model. Collectively, our findings reveal a new property of SdrD as an important key contributor to S. aureus survival and the ability to escape the innate immune system in blood.

scholarly journals Staphylococcus aureus secreted lipases do not inhibit innate immune killing mechanisms

2021 ◽  
Vol 5 ◽  
pp. 286
Author(s):  
Fiona Sargison ◽  
Mariya I Goncheva ◽  
Joana Alves ◽  
Amy Pickering ◽  
J Ross Fitzgerald
Keyword(s):  
Staphylococcus Aureus ◽  
Whole Blood ◽  
Immune Cell ◽  
Innate Immune ◽  
Human Neutrophils ◽  
Bacterial Killing ◽  
Isogenic Mutant ◽  
Extracellular Milieu ◽  
The Impact

Background: Staphylococcus aureus causes an array of diseases in both humans and livestock. Pathogenesis is mediated by a plethora of proteins secreted by S. aureus, many of which remain incompletely characterised. For example, S. aureus abundantly secretes two isoforms of the enzyme lipase into the extracellular milieu, where they scavenge upon polymeric triglycerides. It has previously been suggested that lipases may interfere with the function of innate immune cells, such as macrophages and neutrophils, but the impact of lipases on phagocytic killing mechanisms remains unknown. Methods: We employed the epidemic S. aureus clone USA300 strain LAC and its lipase deficient isogenic mutant, along with recombinant lipase proteins, in in vitro experimental infection assays. To determine if lipases can inhibit innate immune killing mechanisms, the bactericidal activity of whole blood, human neutrophils, and macrophages was analysed. In addition, gentamycin protection assays were carried out to examine the influence of lipases on S. aureus innate immune cell escape. Results: There were no differences in the survival of S. aureus USA300 LAC wild type and its lipase-deficient isogenic mutant after incubation with human whole blood or neutrophils. Furthermore, there was no detectable lipase-dependent effect on phagocytosis, intracellular survival, or escape from both human primary and immortalised cell line macrophages, even upon supplementation with exogenous recombinant lipases. Conclusions: S. aureus lipases do not inhibit bacterial killing mechanisms of human macrophages, neutrophils, or whole blood. These findings broaden our understanding of the interaction of S. aureus with the innate immune system.

scholarly journals Leukocidins and the Nuclease Nuc Prevent Neutrophil-Mediated Killing of Staphylococcus aureus Biofilms

2020 ◽  
Vol 88 (10) ◽  
Author(s):  
Mohini Bhattacharya ◽  
Evelien T. M. Berends ◽  
Xuhui Zheng ◽  
Preston J. Hill ◽  
Rita Chan ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Innate Immune ◽  
Human Neutrophils ◽  
Chronic Infections ◽  
Content Type ◽  
Persistent Infections ◽  
Biofilm Bacteria ◽  
Key Aspects ◽  
Neutrophil Response ◽  
Insight Into

ABSTRACT Bacterial biofilms are linked with chronic infections and have properties distinct from those of planktonic, single-celled bacteria. The virulence mechanisms associated with Staphylococcus aureus biofilms are becoming better understood. Human neutrophils are critical for the innate immune response to S. aureus infection. Here, we describe two virulence strategies that converge to promote the ability of S. aureus biofilms to evade killing by neutrophils. Specifically, we show that while neutrophils exposed to S. aureus biofilms produce extracellular traps (NETs) and phagocytose bacteria, both mechanisms are inefficient in clearance of the biofilm biomass. This is attributed to the leukocidin LukAB, which promotes S. aureus survival during phagocytosis. We also show that the persistence of biofilm bacteria trapped in NETs is facilitated by S. aureus nuclease (Nuc)-mediated degradation of NET DNA. This study describes key aspects of the interaction between primary human neutrophils and S. aureus biofilms and provides insight into how S. aureus evades the neutrophil response to cause persistent infections.

scholarly journals Multi-modal imaging reveals dynamic interactions of Staphylococcus aureus within human neutrophils

2021 ◽  
Author(s):  
Yin Xin Ho ◽  
Elliot Steele ◽  
Lynne Prince ◽  
Ashley Cadby
Keyword(s):  
Staphylococcus Aureus ◽  
Imaging Modality ◽  
Super Resolution ◽  
Cellular Level ◽  
Innate Immune ◽  
Human Neutrophils ◽  
Dynamic Interactions ◽  
Wide Range ◽  
Resolution Imaging ◽  
Super Resolution Microscopy

Staphylococcus aureus is an important human pathogen that causes a wide range of infections. Neutrophils are an essential component of our innate immune system and understanding S. aureus-neutrophil interactions on a sub-cellular level is crucial to developing new therapeutic strategies to promote immunity during S. aureus infections. To this end we have developed a multi-modal imaging platform capable of following host-pathogen processes in biological systems, this is achieved by switching imaging modalities between a low photo-toxicity and low resolution imaging modality through an increasing illumination intensity to achieve live super-resolution imaging. This novel imaging platform was applied to the study of human neutrophils infected by S. aureus. We show that we can image different infection stages of S. aureus in live neutrophils with super resolution microscopy. We see evidence of binary fission occurring in intracellular S. aureus within a neutrophil.

scholarly journals Combined In Vitro Studies and in Silico Target Fishing for the Evaluation of the Biological Activities of Diphylleia cymosa and Podophyllum hexandrum

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3303 ◽  
Author(s):  
Marina Rocha ◽  
Priscilla Campana ◽  
Denise Scoaris ◽  
Vera Almeida ◽  
Julio Lopes ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
In Silico ◽  
Antioxidant Activities ◽  
Biological Activities ◽  
New Drugs ◽  
Podophyllum Hexandrum ◽  
Major Constituent ◽  
Cytotoxic Activities ◽  
Leaves And Roots

This paper reports the in silico prediction of biological activities of lignans from Diphylleia cymosa and Podophyllum hexandrum combined with an in vitro bioassays. The extracts from the leaves, roots and rhizomes of both species were evaluated for their antibacterial, anticholinesterasic, antioxidant and cytotoxic activities. A group of 27 lignans was selected for biological activities prediction using the Active-IT system with 1987 ligand-based bioactivity models. The in silico approach was properly validated and several ethnopharmacological uses and known biological activities were confirmed, whilst others should be investigated for new drugs with potential clinical use. The extracts from roots of D. cymosa and from rhizomes and roots of P. hexandrum were very effective against Bacillus cereus and Staphylococcus aureus, while podophyllotoxin inhibited the growth of Staphylococcus aureus and Escherichia coli. D. cymosa leaves and roots showed anticholinesterasic and antioxidant activities, respectively. The evaluated extracts showed to be moderately toxic to THP-1 cells. The chromatographic characterization indicated that podophyllotoxin was the major constituent of P. hexandrum extract while kaempferol and its hexoside were the main constituents of D. cymosa leaves and roots, respectively. These results suggest that the podophyllotoxin could be the major antibacterial lignan, while flavonoids could be responsible for the antioxidant activity.

scholarly journals Immune evasion by Staphylococcus aureus conferred by iron-regulated surface determinant protein IsdH

Microbiology ◽  
2009 ◽  
Vol 155 (3) ◽  
pp. 667-679 ◽  
Author(s):  
Livia Visai ◽  
Naoko Yanagisawa ◽  
Elisabet Josefsson ◽  
Andrej Tarkowski ◽  
Ilaria Pezzali ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Responses ◽  
Innate Immune ◽  
Human Neutrophils ◽  
Protective Mechanism ◽  
Innate Immune Responses ◽  
Null Mutant ◽  
Wild Type ◽  
Accelerated Degradation ◽  
Associated Proteins

The ability of Staphylococcus aureus to avoid innate immune responses including neutrophil-mediated phagocytosis is crucial for the organism to cause infection. This multifactorial process involves several secreted and cell-surface-associated proteins. In this paper we report a novel mechanism of combating neutrophils that involves iron-regulated surface determinant protein H (IsdH). The IsdH protein is part of a complex that is only expressed under iron-restricted conditions in order to bind haemoglobin and extract and transport haem into the cytoplasm. A null mutant defective in expression of IsdH, and mutants expressing variants of IsdH with substitutions in residues predicted to be involved in ligand binding, were generated from S. aureus 8325-4. The IsdH-defective mutants were shown by several measures to have reduced virulence compared with the wild-type. The mutant was engulfed more rapidly by human neutrophils in the presence of serum opsonins, survived poorly in fresh whole human blood and was less virulent in a mouse model of sepsis. The protective mechanism seems to stem from an accelerated degradation of the serum opsonin C3b.

scholarly journals Staphylococcus aureus secreted lipases do not inhibit innate immune killing mechanisms

2020 ◽  
Vol 5 ◽  
pp. 286
Author(s):  
Fiona Sargison ◽  
Joana Alves ◽  
Amy Pickering ◽  
J Ross Fitzgerald
Keyword(s):  
Staphylococcus Aureus ◽  
Whole Blood ◽  
Immune Cell ◽  
Innate Immune ◽  
Human Neutrophils ◽  
Bacterial Killing ◽  
Isogenic Mutant ◽  
Extracellular Milieu ◽  
The Impact

Background: Staphylococcus aureus causes an array of diseases in both humans and livestock. Pathogenesis is mediated by a plethora of proteins secreted by S. aureus, many of which remain incompletely characterised. For example, S. aureus abundantly secretes two isoforms of the enzyme lipase into the extracellular milieu, where they scavenge upon polymeric triglycerides. It has previously been suggested that lipases may interfere with the function of innate immune cells, such as macrophages and neutrophils, but the impact of lipases on phagocytic killing mechanisms remains unknown. Methods: We employed the epidemic S. aureus clone USA300 strain LAC and its lipase deficient isogenic mutant, along with recombinant lipase proteins, in in vitro experimental infection assays. To determine if lipases can inhibit innate immune killing mechanisms, the bactericidal activity of whole blood, human neutrophils, and macrophages was analysed. In addition, gentamycin protection assays were carried out to examine the influence of lipases on S. aureus innate immune cell escape. Results: There were no differences in the survival of S. aureus USA300 LAC wild type and its lipase-deficient isogenic mutant after incubation with human whole blood or neutrophils. Furthermore, there was no detectable lipase-dependent effect on phagocytosis, intracellular survival, or escape from both human primary and immortalised cell line macrophages, even upon supplementation with exogenous recombinant lipases. Conclusions: S. aureus lipases do not inhibit bacterial killing mechanisms of human macrophages, neutrophils, or whole blood. These findings broaden our understanding of the interaction of S. aureus with the innate immune system.

scholarly journals The Role of Cell Metabolism in Innate Immune Memory

2020 ◽  
pp. 1-9
Author(s):  
Anaisa Valido Ferreira ◽  
Jorge Domiguéz-Andrés ◽  
Mihai Gheorghe Netea
Keyword(s):  
Metabolic Pathways ◽  
Tricarboxylic Acid Cycle ◽  
Cell Metabolism ◽  
Innate Immune ◽  
Immune Memory ◽  
Functional Changes ◽  
Trained Immunity ◽  
Health And Disease

Immunological memory is classically attributed to adaptive immune responses, but recent studies have shown that challenged innate immune cells can display long-term functional changes that increase nonspecific responsiveness to subsequent infections. This phenomenon, coined <i>trained immunity</i> or <i>innate immune memory</i>, is based on the epigenetic reprogramming and the rewiring of intracellular metabolic pathways. Here, we review the different metabolic pathways that are modulated in trained immunity. Glycolysis, oxidative phosphorylation, the tricarboxylic acid cycle, amino acid, and lipid metabolism are interplaying pathways that are crucial for the establishment of innate immune memory. Unraveling this metabolic wiring allows for a better understanding of innate immune contribution to health and disease. These insights may open avenues for the development of future therapies that aim to harness or dampen the power of the innate immune response.

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