Staphylococci evade the innate immune response by disarming neutrophils and forming biofilms

Vor, Lisanne de; Rooijakkers, Suzan H.M.; Strijp, Jos A. G. van

doi:10.1002/1873-3468.13767

Cited by 78 publications

(65 citation statements)

References 104 publications

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“…One key element of S. aureus pathophysiology is the ability of biofilms to circumvent host immune attacks [8]. During S. aureus cutaneous infections, tissue-resident mast cells recruit neutrophils and monocytes/macrophages from the bloodstream [9] along with monocytic myeloid-derived suppressor cells (M-MDSCs) in interaction with natural killer (NK) cells to promote the first level of inflammatory responses [10].…”

Section: Introductionmentioning

confidence: 99%

Biofilm-coated microbeads and the mouse ear skin: An innovative model for analysing anti-biofilm immune response in vivo

et al. 2020

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Owing to its ability to form biofilms, Staphylococcus aureus is responsible for an increasing number of infections on implantable medical devices. The aim of this study was to develop a mouse model using microbeads coated with S. aureus biofilm to simulate such infections and to analyse the dynamics of anti-biofilm inflammatory responses by intravital imaging. Scanning electron microscopy and flow cytometry were used in vitro to study the ability of an mCherry fluorescent strain of S. aureus to coat silica microbeads. Biofilm-coated microbeads were then inoculated intradermally into the ear tissue of LysM-EGFP transgenic mice (EGFP fluorescent immune cells). General and specific real-time inflammatory responses were studied in ear tissue by confocal microscopy at early (4-6h) and late time points (after 24h) after injection. The displacement properties of immune cells were analysed. The responses were compared with those obtained in control mice injected with only microbeads. In vitro, our protocol was capable of generating reproducible inocula of biofilm-coated microbeads verified by labelling matrix components, observing biofilm ultrastructure and confirmed in vivo and in situ with a matrix specific fluorescent probe. In vivo, a major inflammatory response was observed in the mouse ear pinna at both time points. Real-time observations of cell recruitment at injection sites showed that immune cells had difficulty in accessing biofilm bacteria and highlighted areas of direct interaction. The average speed of cells was lower in infected mice compared to control mice and in tissue areas where direct contact between immune cells and bacteria was observed, the average cell velocity and linearity were decreased in comparison to cells in areas where no bacteria were visible. This model provides an innovative way to analyse specific immune responses against biofilm infections on medical devices. It paves the way for live evaluation of the effectiveness of immunomodulatory therapies combined with antibiotics.

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Section: Introductionmentioning

confidence: 99%

Biofilm-coated microbeads and the mouse ear skin: An innovative model for analysing anti-biofilm immune response in vivo

et al. 2020

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“…The isolation of antibiotic resistant strains is continuously increasing [ 55 , 56 , 57 ]. Moreover, their attachment to host tissues, as well as to medical implants and the production of biofilm, play an important role in the persistence of these infections [ 58 , 59 ]. The establishment of a mature biofilm, which is significantly less sensitive to antimicrobial agents than genetically identical non-adherent planktonic cells, considerably delays the healing process [ 4 , 60 , 61 ].…”

Section: Resultsmentioning

confidence: 99%

Anti-Biofilm Activity of the Fungal Phytotoxin Sphaeropsidin A against Clinical Isolates of Antibiotic-Resistant Bacteria

Roscetto

Masi²,

Esposito

et al. 2020

Toxins

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Many pathogens involved in human infection have rapidly increased their antibiotic resistance, reducing the effectiveness of therapies in recent decades. Most of them can form biofilms and effective drugs are not available to treat these formations. Natural products could represent an efficient solution in discovering and developing new drugs to overcome antimicrobial resistance and treat biofilm-related infections. In this study, 20 secondary metabolites produced by pathogenic fungi of forest plants and belonging to diverse classes of naturally occurring compounds were evaluated for the first time against clinical isolates of antibiotic-resistant Gram-negative and Gram-positive bacteria. epi-Epoformin, sphaeropsidone, and sphaeropsidin A showed antimicrobial activity on all test strains. In particular, sphaeropsidin A was effective at low concentrations with Minimum Inhibitory Concentration (MIC) values ranging from 6.25 μg/mL to 12.5 μg/mL against all reference and clinical test strains. Furthermore, sphaeropsidin A at sub-inhibitory concentrations decreased methicillin-resistant S. aureus (MRSA) and P. aeruginosa biofilm formation, as quantified by crystal violet staining. Interestingly, mixtures of sphaeropsidin A and epi-epoformin have shown antimicrobial synergistic effects with a concomitant reduction of cytotoxicity against human immortalized keratinocytes. Our data show that sphaeropsidin A and epi-epoformin possess promising antimicrobial properties.

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“…When challenged by planktonic bacteria, the innate immune response is highly efficient in its clearance of bacteria but the presence of bacterial biofilms has been associated with an increased resistance to host defences [66,67]. Mechanisms of biofilm-specific immune evasion include mechanical protection, shielding from immune recognition, changes in gene expression and inhibition of immune cell functions [68][69][70]. It is important to note that there are differences in the immune evasion strategies used by different bacterial species (heavily influenced by EPS composition), but this review is focused solely on S. aureus and P. aeruginosa.…”

Section: Immune Evasion In Biofilmsmentioning

confidence: 99%

“…In other staphylococcal strains, polymeric-N-acetyl-glucosamine (PNAG) has been described as an antibody "sink" and is shown to protect against the binding of IgG and C3b to biofilm-bacteria [77,78]. Although this has not been demonstrated in S. aureus, it is possible that similar principles could apply, with EPS components acting as decoys for opsonisation and/or preventing direct targeting of the biofilm bacteria [70]. In P. aeruginosa, alginate and Psl polysaccharide are major components of the EPS.…”

Section: Immune Recognitionmentioning

confidence: 99%

“…The upregulation of genes encoding toxins and immune evasion proteins plays a major role in the increased immune resistance of S. aureus biofilms. Upregulated toxins include Hla, LukAB/GH, LukED, HlgAB, HlgCB and PSMs and upregulated immune evasion proteins include Eap, CHIPS, SAK and SSL10 [70]. Gene expression is controlled by the accessory gene regulator (Agr) quorum sensing (QS) system [82].…”

Section: Changes In Gene Expressionmentioning

confidence: 99%

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Corneal Infection Models: Tools to Investigate the Role of Biofilms in Bacterial Keratitis

Urwin

Okurowska

Crowther

et al. 2020

Cells

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Bacterial keratitis is a corneal infection which may cause visual impairment or even loss of the infected eye. It remains a major cause of blindness in the developing world. Staphylococcus aureus and Pseudomonas aeruginosa are common causative agents and these bacterial species are known to colonise the corneal surface as biofilm populations. Biofilms are complex bacterial communities encased in an extracellular polymeric matrix and are notoriously difficult to eradicate once established. Biofilm bacteria exhibit different phenotypic characteristics from their planktonic counterparts, including an increased resistance to antibiotics and the host immune response. Therefore, understanding the role of biofilms will be essential in the development of new ophthalmic antimicrobials. A brief overview of biofilm-specific resistance mechanisms is provided, but this is a highly multifactorial and rapidly expanding field that warrants further research. Progression in this field is dependent on the development of suitable biofilm models that acknowledge the complexity of the ocular environment. Abiotic models of biofilm formation (where biofilms are studied on non-living surfaces) currently dominate the literature, but co-culture infection models are beginning to emerge. In vitro, ex vivo and in vivo corneal infection models have now been reported which use a variety of different experimental techniques and animal models. In this review, we will discuss existing corneal infection models and their application in the study of biofilms and host-pathogen interactions at the corneal surface.

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Staphylococci evade the innate immune response by disarming neutrophils and forming biofilms

Cited by 78 publications

References 104 publications

Biofilm-coated microbeads and the mouse ear skin: An innovative model for analysing anti-biofilm immune response in vivo

Biofilm-coated microbeads and the mouse ear skin: An innovative model for analysing anti-biofilm immune response in vivo

Anti-Biofilm Activity of the Fungal Phytotoxin Sphaeropsidin A against Clinical Isolates of Antibiotic-Resistant Bacteria

Corneal Infection Models: Tools to Investigate the Role of Biofilms in Bacterial Keratitis

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