scholarly journals Laboratory Mice Are Frequently Colonized with Staphylococcus aureus and Mount a Systemic Immune Response—Note of Caution for In vivo Infection Experiments

2017 ◽  
Vol 7 ◽  
Author(s):  
Daniel Schulz ◽  
Dorothee Grumann ◽  
Patricia Trübe ◽  
Kathleen Pritchett-Corning ◽  
Sarah Johnson ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Response ◽  
Laboratory Mice ◽  
Systemic Immune Response ◽  
Infection Experiments

scholarly journals The presence of Syphacia obvelata in laboratory mice (BALB/c) — parasite antigens in immune response

2006 ◽  
Vol 43 (4) ◽  
pp. 203-207 ◽  
Author(s):  
A. Perec ◽  
A. Okulewicz
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Infection Control ◽  
Diagnostic Test ◽  
Laboratory Mice ◽  
Systemic Immune Response ◽  
Immunogenic Proteins ◽  
Syphacia Obvelata ◽  
Somatic Antigens ◽  
Mucosal Igg

AbstractIn conventional mice colonies, mouse pinworm, Syphacia obvelata is found very often. Several studies indicate that infection with this parasite can modulate the immune system of the host and can affect experimental final results. The aim of our study was to investigate the most immunogenic proteins of S. obvelata inducing both local and systemic immune response in naturally infected laboratory mice. Protein extracts of S. obvelata were analysed by Western blotting to examine their antigenic character. The antigens were probed with serum and mucosa of S. obvelata naturally infected mice. Surface and somatic antigens were recognized by serum and mucosal IgG, IgA and IgM antibodies. The most immunogenic and dominant proteins were observed. Proteins of Mw ∼ 70, 65 and 48 kDa showed the most evident reaction with serum and mucosa antibodies of infected animals. Surface and somatic antigens of nematode S. obvelata eliciting immune response in laboratory mice may be useful in development of a diagnostic test which could be applied for the infection control prior the experiments.

scholarly journals Identification of Staphylococcus aureus Proteins Recognized by the Antibody-Mediated Immune Response to a Biofilm Infection

2006 ◽  
Vol 74 (6) ◽  
pp. 3415-3426 ◽  
Author(s):  
Rebecca A. Brady ◽  
Jeff G. Leid ◽  
Anne K. Camper ◽  
J. William Costerton ◽  
Mark E. Shirtliff
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Response ◽  
Immune System ◽  
Two Dimensional Gel Electrophoresis ◽  
A Cell ◽  
Microarray Analyses ◽  
Gene Expression Levels ◽  
Biofilm Infection

ABSTRACT Staphylococcus aureus causes persistent, recurrent infections (e.g., osteomyelitis) by forming biofilms. To survey the antibody-mediated immune response and identify those proteins that are immunogenic in an S. aureus biofilm infection, the tibias of rabbits were infected with methicillin-resistant S. aureus to produce chronic osteomyelitis. Sera were collected prior to infection and at 14, 28, and 42 days postinfection. The sera were used to perform Western blot assays on total protein from biofilm grown in vitro and separated by two-dimensional gel electrophoresis. Those proteins recognized by host antibodies in the harvested sera were identified via matrix-assisted laser desorption ionization-time of flight analysis. Using protein from mechanically disrupted total and fractionated biofilm protein samples, we identified 26 and 22 immunogens, respectively. These included a cell surface-associated β-lactamase, lipoprotein, lipase, autolysin, and an ABC transporter lipoprotein. Studies were also performed using microarray analyses and confirmed the biofilm-specific up-regulation of most of these genes. Therefore, although the biofilm antigens are recognized by the immune system, the biofilm infection can persist. However, these proteins, when delivered as vaccines, may be important in directing the immune system toward an early and effective antibody-mediated response to prevent chronic S. aureus infections. Previous works have identified S. aureus proteins that are immunogenic during acute infections, such as sepsis. However, this is the first work to identify these immunogens during chronic S. aureus biofilm infections and to simultaneously show the global relationship between the antigens expressed during an in vivo infection and the corresponding in vitro transcriptomic and proteomic gene expression levels.

scholarly journals Development of a Conserved Chimeric Vaccine for Induction of Strong Immune Response against Staphylococcus aureus Using Immunoinformatics Approaches

Vaccines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1038
Author(s):  
Rahul Chatterjee ◽  
Panchanan Sahoo ◽  
Soumya Ranjan Mahapatra ◽  
Jyotirmayee Dey ◽  
Mrinmoy Ghosh ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Response ◽  
Multidrug Resistant ◽  
Host Cells ◽  
Dynamics Simulation ◽  
Population Coverage ◽  
Strong Immune Response ◽  
Chimeric Vaccine

Staphylococcus aureus is one of the most notorious Gram-positive bacteria with a very high mortality rate. The WHO has listed S. aureus as one of the ESKAPE pathogens requiring urgent research and development efforts to fight against it. Yet there is a major layback in the advancement of effective vaccines against this multidrug-resistant pathogen. SdrD and SdrE proteins are attractive immunogen candidates as they are conserved among all the strains and contribute specifically to bacterial adherence to the host cells. Furthermore, these proteins are predicted to be highly antigenic and essential for pathogen survival. Therefore, in this study, using the immunoinformatics approach, a novel vaccine candidate was constructed using highly immunogenic conserved T-cell and B-cell epitopes along with specific linkers, adjuvants, and consequently modeled for docking with human Toll-like receptor 2. Additionally, physicochemical properties, secondary structure, disulphide engineering, and population coverage analysis were also analyzed for the vaccine. The constructed vaccine showed good results of worldwide population coverage and a promising immune response. For evaluation of the stability of the vaccine-TLR-2 docked complex, a molecular dynamics simulation was performed. The constructed vaccine was subjected to in silico immune simulations by C-ImmSim and Immune simulation significantly provided high levels of immunoglobulins, T-helper cells, T-cytotoxic cells, and INF-γ. Lastly, upon cloning, the vaccine protein was reverse transcribed into a DNA sequence and cloned into a pET28a (+) vector to ensure translational potency and microbial expression. The overall results of the study showed that the designed novel chimeric vaccine can simultaneously elicit humoral and cell-mediated immune responses and is a reliable construct for subsequent in vivo and in vitro studies against the pathogen.

scholarly journals Biofilm Matrix Exoproteins Induce a Protective Immune Response against Staphylococcus aureus Biofilm Infection

2013 ◽  
Vol 82 (3) ◽  
pp. 1017-1029 ◽  
Author(s):  
Carmen Gil ◽  
Cristina Solano ◽  
Saioa Burgui ◽  
Cristina Latasa ◽  
Begoña García ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Response ◽  
Extracellular Proteins ◽  
Protective Immune Response ◽  
Surrounding Tissue ◽  
Bacterial Cells ◽  
Content Type ◽  
Biofilm Infection ◽  
Biofilm Matrix

ABSTRACTTheStaphylococcus aureusbiofilm mode of growth is associated with several chronic infections that are very difficult to treat due to the recalcitrant nature of biofilms to clearance by antimicrobials. Accordingly, there is an increasing interest in preventing the formation ofS. aureusbiofilms and developing efficient antibiofilm vaccines. Given the fact that during a biofilm-associated infection, the first primary interface between the host and the bacteria is the self-produced extracellular matrix, in this study we analyzed the potential of extracellular proteins found in the biofilm matrix to induce a protective immune response againstS. aureusinfections. By using proteomic approaches, we characterized the exoproteomes of exopolysaccharide-based and protein-based biofilm matrices produced by two clinicalS. aureusstrains. Remarkably, results showed that independently of the nature of the biofilm matrix, a common core of secreted proteins is contained in both types of exoproteomes. Intradermal administration of an exoproteome extract of an exopolysaccharide-dependent biofilm induced a humoral immune response and elicited the production of interleukin 10 (IL-10) and IL-17 in mice. Antibodies against such an extract promoted opsonophagocytosis and killing ofS. aureus. Immunization with the biofilm matrix exoproteome significantly reduced the number of bacterial cells inside a biofilm and on the surrounding tissue, using anin vivomodel of mesh-associated biofilm infection. Furthermore, immunized mice also showed limited organ colonization by bacteria released from the matrix at the dispersive stage of the biofilm cycle. Altogether, these data illustrate the potential of biofilm matrix exoproteins as a promising candidate multivalent vaccine againstS. aureusbiofilm-associated infections.

scholarly journals The Role of Antibiotics in Modulating Virulence in Staphylococcus aureus

2017 ◽  
Vol 30 (4) ◽  
pp. 887-917 ◽  
Author(s):  
Elisabeth Hodille ◽  
Warren Rose ◽  
Binh An Diep ◽  
Sylvain Goutelle ◽  
Gerard Lina ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Response ◽  
Virulence Factors ◽  
Growth Models ◽  
Case Reports ◽  
Suppressive Effect ◽  
Bacterial Strains ◽  
Content Type

SUMMARY Staphylococcus aureus is often involved in severe infections, in which the effects of bacterial virulence factors have great importance. Antistaphylococcal regimens should take into account the different effects of antibacterial agents on the expression of virulence factors and on the host's immune response. A PubMed literature search was performed to select relevant articles on the effects of antibiotics on staphylococcal toxin production and on the host immune response. Information was sorted according to the methods used for data acquisition (bacterial strains, growth models, and antibiotic concentrations) and the assays used for readout generation. The reported mechanisms underlying S. aureus virulence modulation by antibiotics were reviewed. The relevance of in vitro observations is discussed in relation to animal model data and to clinical evidence extracted from case reports and recommendations on the management of toxin-related staphylococcal diseases. Most in vitro data point to a decreased level of virulence expression upon treatment with ribosomally active antibiotics (linezolid and clindamycin), while cell wall-active antibiotics (beta-lactams) mainly increase exotoxin production. In vivo studies confirmed the suppressive effect of clindamycin and linezolid on virulence expression, supporting their utilization as a valuable management strategy to improve patient outcomes in cases of toxin-associated staphylococcal disease.

scholarly journals 869 Locally administered immunotherapy self-delivering RNAi PH-762 results in abscopal clearance of untreated distal tumors, suggesting systemic immune response, in a murine hepatocarcinoma model

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A910-A910
Author(s):  
Benjamin Cuiffo ◽  
Melissa Maxwell ◽  
Dingxue Yan ◽  
Brianna Rivest ◽  
James Cardia ◽  
...  
Keyword(s):  
Immune Response ◽  
Tumor Growth ◽  
Mechanism Of Action ◽  
Systemic Toxicity ◽  
Published Data ◽  
Abscopal Effect ◽  
Systemic Immune Response ◽  
In Vivo Efficacy

BackgroundThe development of locally administered immune checkpoint inhibition (ICI) holds potential promise for enhanced activity and decreased systemic toxicity, but such an approach is challenging with the available ICI antibodies. We have previously shown that the intratumoral (IT) delivery of PH-762, a self-delivering RNAi compound targeting PD-1 based on proprietary INTASYL™ technology, can significantly inhibit tumor growth associated with changes in the immune cell population in the tumor microenvironment towards an anti-tumor phenotype. We present data showing that IT administration of PH-762 not only inhibits local tumor growth but can also elicit an abscopal effect in distal untreated tumors. The in vivo efficacy and in vitro mechanism of action support the generation of a PH-762 driven systemic anti-tumor immune response. Therefore, ICI using INTASYL is an alternative to antibody drugs for immunotherapy.MethodsTo assess in vivo efficacy, Hepa1–6 cells were implanted subcutaneously into the flanks of C57BL/6J mice. Vehicle (PBS) or murine targeting PH-762 (mPH-762) were administered IT on Days 1, 4, 7, 10 and 14. To determine an abscopal effect cells were also implanted into the opposite flank but left untreated. Tumor volumes and body weights were recorded. In addition, in vitro mechanism of action studies were performed with CD3-stimulated human pan T cells. PD-1 mRNA knockdown was assessed by qRT-PCR; PD-1 protein expression by flow cytometry; and T cell function by cytokine release.ResultsTreatment with IT administered mPH-762 significantly inhibited tumor growth compared with vehicle treated control tumors. Furthermore, the growth of the untreated bilateral tumor was significantly reduced with 80% of these tumors showing complete regression. Mechanism of action studies showed potent and durable silencing of PD-1. Increased release of IFN-γ, CXCL10, and IL-6 and suppression of IL-10 release were indicators of an enhanced immune response.ConclusionsThese data show that silencing PD-1 with IT administration of mPH-762 not only inhibits growth of treated tumors but elicits an abscopal effect leading to cure of distal tumors. This data and other recently published data showing evidence of a specific antitumor immune response in a tumor rechallenge model after prior treatment with INTASYL compounds, demonstrate the desired systemic immune response can be obtained with local administration of PH-762. INTASYL represent an alternative to antibody therapy for IT checkpoint blockade with potential for improved efficacy and reduced systemic toxicity which will be investigated in an upcoming clinical trial.

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