Feasibility of using a combination of staphylococcal superantigen-like proteins 3, 7 and 11 in a fusion vaccine for Staphylococcus aureus.

Staphylococcus aureus is a significant bacterial pathogen in both community and hospital settings, and the escalation of antimicrobial-resistant strains is of immense global concern. Vaccination is an inviting long-term strategy to curb staphylococcal disease, but identification of an effective vaccine has proved to be challenging. Three well-characterized, ubiquitous, secreted immune evasion factors from the staphylococcal superantigen-like (SSL) protein family were selected for the development of a vaccine.

Different Group A Streptococcus pili lead to varying proinflammatory cytokine responses and virulence.

The human pathogen Streptococcus pyogenes, or Group A Streptococcus (GAS), is associated with a variety of diseases ranging from mild skin and soft tissue infections to invasive diseases and immune sequelae such as rheumatic heart disease. We have recently reported that one of the virulence factors of this pathogen, the pilus, has inflammatory properties and strongly stimulates the innate immune system. Here we used a range of nonpathogenic Lactococcus lactis gain-of-function mutants, each expressing one of the major pilus types of GAS, to compare the immune responses generated by various types of fully assembled pili.

The Effect of Amoxicillin with Clavulanate on the Microbiota of Tonsillar Tissue in Disease: a Randomized Control Trial.

Despite antibiotics being the primary medical treatment for recurrent tonsillitis, the impact of antibiotics on the tonsillar microbiome is not well understood. This study aimed to determine the effect of amoxicillin with clavulanate on the composition and quantity of bacteria in the tonsils of children with recurrent tonsillitis. A multicenter randomized clinical trial in Auckland, New Zealand was undertaken between August 1, 2017, and June 30, 2018.

The histological and microbiological characteristics of bacterial microcolonies in paediatric tonsillar hyperplasia.

Introduction: Paediatric tonsillar hyperplasia (TH) is associated with a spectrum of presentations ranging from recurrent tonsillitis (RT) to sleep-disordered breathing (SDB). The underlying pathogenesis of tonsillar hyperplasia remains poorly understood. Previous studies have implicated bacterial microcolonies as targets of host inflammatory cells and as a potential driver of the chronic inflammation seen in TH.

Pilus proteins from Streptococcus pyogenes stimulate innate immune responses through Toll-like receptor 2.

The group A Streptococcus (GAS) pilus is a long, flexible, hair-like structure anchored to the cell surface that facilitates the adherence of GAS to host cells, thus playing a critical role in initiating infections. Because of its important role in GAS virulence, the pilus has become an attractive target for vaccine development. While current research mainly focuses on pilus function and its potential as a vaccine component, there is a lack of knowledge on how the host immune system recognizes and responds to this abundant surface structure.

Characterising clinical Staphylococcus aureus isolates from the sinuses of patients with chronic rhinosinusitis.

The role of Staphylococcus aureus in the pathogenesis of the chronic sinonasal disease chronic rhinosinusitis (CRS), has not been definitively established. Comparative analyses of S. aureus isolates from CRS with those from control participants may offer insight into a possible pathogenic link between this organism and CRS.

Sinonasal Tissue Remodelling during Chronic Rhinosinusitis.

The purpose of this review is to summarise contemporary knowledge of sinonasal tissue remodelling during chronic rhinosinusitis (CRS), a chronic disease involving long-term inflammation of the paranasal sinuses and nasal passage. The concept of tissue remodelling has significant clinical relevance because of its potential to cause irreversibility in chronic airway tissues. Recent studies have indicated that early surgical treatment of CRS may improve clinical outcome.

PilVax, a novel Lactococcus lactis-based mucosal vaccine platform, stimulates systemic and mucosal immune responses to Staphylococcus aureus.

Most pathogens initiate infection via the mucosa, therefore delivery of vaccines directly to the mucosa is likely to be advantageous for stimulating protective immunity at the site of entry. PilVax is a novel mucosal vaccine platform that harnesses Lactococcus lactis bacteria engineered to stably express multiple copies of vaccine peptide antigens within pili, hair-like structures which extend from the cell wall. This strategy elicited systemic and mucosal antibody responses to a model antigen after intranasal immunization, but has not been tested for its capacity to stimulate protective mucosal immunity.

Feasibility of Using a Luminescence-Based Method to Determine Serum Bactericidal Activity against .

Development of a vaccine to limit the impact of antibiotic resistant is now a global priority. Serum bactericidal antibody (SBA) is a possible indicator of protective immunity to , but conventional assays measure colony forming units (CFU), which is time-consuming. A luminescent assay that quantifies ATP as a surrogate measure of bacterial viability was tested on strains FA1090, MS11 and P9-17 and compared to CFU-based readouts.

Impact of Superantigen-Producing Bacteria on T Cells from Tonsillar Hyperplasia.

and Group A Streptococcus (GAS) are common occupants of the tonsils and many strains produce potent exotoxins (mitogens) that directly target T cells, which could be a driver for tonsillar hyperplasia. Tonsil tissues from 41 patients were tested for these bacteria in conjunction with profiling of B and T cells by flow cytometry. and GAS were detected in tonsil tissue from 44% and 7%, respectively, of patients by bacteriological culture; immuno-histology showed bacteria in close proximity to both B and T lymphocytes.

Exploitation of Group B OMV Vaccines Against to Inform the Development and Deployment of Effective Gonorrhea Vaccines.

Have potential clues to an effective gonorrhea vaccine been lurking in international disease surveillance data for decades? While no clinically effective vaccines against gonorrhea have been developed we present direct and indirect evidence that a vaccine is not only possible, but may already exist. Experience from Cuba, New Zealand, and Canada suggest that vaccines containing Group B outer membrane vesicles (OMV) developed to control type-specific meningococcal disease may also prevent a significant proportion of gonorrhea. The mechanisms for this phenomenon have not yet been elucidated but we present some strategies for unraveling potential cross protective antigens and effector immune responses by exploiting stored sera from clinical trials and individuals primed with a meningococcal group B OMV vaccine (MeNZB).

Microbial and inflammatory-based salivary biomarkers of head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) patients often present with poor oral health, making it difficult to assess the relationship between oral microbes, inflammation, and carcinoma. This study investigates salivary microbes and inflammatory cytokines as biomarkers for HNSCC, with consideration of oral health. Saliva was collected from 30 participants, including 14 HNSCC patients and 16 participants representing both dentally compromised and healthy individuals.

Pathogen reservoir hypothesis investigated by analyses of the adenotonsillar and middle ear microbiota.

Introduction: Adenotonsillar and middle ear diseases result in some of the most frequently performed operations in the pediatric population worldwide. The pathogen reservoir hypothesis (PRH) suggests that the adenoids act as a reservoir of bacteria which play a potential pathogenic role in otitis media. Evidence supporting this hypothesis is limited.

Inflammatory Endotypes and Microbial Associations in Chronic Rhinosinusitis.

A complex mix of inflammatory and microbial associations underscores the chronic inflammatory condition chronic rhinosinusitis (CRS), and the etiology remains poorly understood. Recent work has begun to delineate between variants (endotypes) of CRS on the basis of inflammatory biomarkers. This study aimed to assess inflammatory patterns in CRS phenotypes, identify putative endotypes of CRS, and to assess inflammatory associations with the sinonasal microbiota.

Paired analysis of the microbiota between surface tissue swabs and biopsies from pediatric patients undergoing adenotonsillectomy.

Introduction: Culture-independent methods, based on bacterial 16 S rRNA gene sequencing, have been used previously to investigate the adenotonsillar microbiota. However, these studies have focused on a single sampling site (usually a surface swab). We aimed to investigate potential differences in adenotonsillar microbiota according to sampling location, both on and within the adenoids and palatine tonsils.

The bacterial community and local lymphocyte response are markedly different in patients with recurrent tonsillitis compared to obstructive sleep apnoea.

Introduction: Obstructive sleep apnea (OSA) is now a more common indication for tonsillectomy than recurrent tonsillitis (RT) [1,2]. Few studies have addressed possible differences in pathogenesis between these two conditions. Children with RT and OSA are often being treated in the community with multiple courses of antibiotics before surgery.

Staphylococcal enterotoxin-like X (SElX) is a unique superantigen with functional features of two major families of staphylococcal virulence factors.

Staphylococcus aureus is an opportunistic pathogen that produces many virulence factors. Two major families of which are the staphylococcal superantigens (SAgs) and the Staphylococcal Superantigen-Like (SSL) exoproteins. The former are immunomodulatory toxins that induce a Vβ-specific activation of T cells, while the latter are immune evasion molecules that interfere with a wide range of innate immune defences.

The in vitro mucolytic effect of xylitol and dornase alfa on chronic rhinosinusitis mucus.

Background: The overproduction and stagnation of purulent mucus impair mucociliary clearance and exacerbate the symptoms of chronic rhinosinusitis (CRS). There is a clinical need for effective topical mucolytic agents to facilitate removal of mucus and improve postoperative outcomes.

Methods: The effects of xylitol (5%) and dornase alfa (1 mg/mL) on mucus and mucus crusts were investigated.

A potential role for staphylococcal and streptococcal superantigens in driving skewing of TCR Vβ subsets in tonsillar hyperplasia.

The TCR Vβ repertoire from patients with recurrent tonsillitis and/or tonsillar hyperplasia was examined to determine whether the TCR Vβ composition is suggestive of local superantigen activity and if so, whether it is associated with the presence of superantigen producing bacteria. Tonsil specimens were cultured aerobically to allow identification and isolation of the bacterial pathogens Staphylococcus aureus and Group A Streptococcus. TCR Vβ subset analysis of tonsil leucocytes was performed by flow cytometry.

Toll-like receptor activation by sino-nasal mucus in chronic rhinosinusitis.

Background: The sino-nasal disease chronic rhinosinusitis (CRS) is primarily an inflammatory condition that manifests in several ways. However, the aetiology of this complex disease is poorly understood. The aim of this study was to explore the association between toll-like receptor (TLR) activation, host immune response and sino-nasal mucus in healthy and diseased patients.

The in vitro effect of xylitol on chronic rhinosinusitis biofilms.

Introduction: Biofilms have been implicated in chronic rhinosinusitis (CRS) and may explain the limited efficacy of antibiotics. There is a need to find more effective, non-antibiotic based therapies for CRS. This study examines the effects of xylitol on CRS biofilms and planktonic bacteria.

Vaccination with Streptococcus pyogenes nuclease A stimulates a high antibody response but no protective immunity in a mouse model of infection.

Streptococcus pyogenes is a human pathogen which causes a spectrum of diseases ranging from pharyngitis to rheumatic fever, necrotising fasciitis and toxic shock syndrome. Development of a vaccine for S. pyogenes has been confounded both by the diversity of the disease-causing serotypes and the spectre of inadvertently stimulating autoimmunity.

Characterization of a mouse-adapted Staphylococcus aureus strain.

More effective antibiotics and a protective vaccine are desperately needed to combat the 'superbug' Staphylococcus aureus. While in vivo pathogenicity studies routinely involve infection of mice with human S. aureus isolates, recent genetic studies have demonstrated that S.

Full functional activity of SSL7 requires binding of both complement C5 and IgA.

Staphylococcus aureus is an opportunistic bacterial pathogen responsible for a range of diseases, from local skin infections through to life-threatening illnesses such as toxic shock syndrome. S. aureus produces an assortment of molecules designed to evade or subvert the host immune system.