Search

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. Wild‐type SSL3, 7 and 11, which inhibit signaling through Toll‐like receptor 2, cleavage of complement component 5 and neutrophil function, respectively, were successfully combined into a stable, active fusion protein (PolySSL7311). Vaccination of mice with an attenuated form of the PolySSL7311 protein stimulated significantly elevated specific immunoglobulin G and splenocyte proliferation responses to each component relative to adjuvant‐only controls. Vaccination with PolySSL7311, but not a mixture of the individual proteins, led to a > 102 reduction in S. aureus tissue burden compared with controls after peritoneal challenge. Comparable antibody responses were elicited after coadministration of the vaccine in either AddaVax (an analog of MF59) or an Alum‐based adjuvant; but only AddaVax conferred a significant reduction in bacterial load, aligning with other studies that suggest both cellular and humoral immune responses are necessary for protective immunity to S. aureus. Anti‐sera from mice immunized with PolySSL7311, but not individual proteins, partially neutralized the functional activities of SSL7. This study confirms the importance of these SSLs for the survival of S. aureus in vivo and suggests that PolySSL7311 is a promising vaccine candidate. [ABSTRACT FROM AUTHOR]

Despite advances in diagnostics and therapeutics, the clinical and economic burdens of Staphylococcus aureus infections remain a substantial public health problem (1). During the past decade in several parts of [...]

A modeling approach is used to study the performance of lead zirconate titanate (PZT)-driven piezoelectric micromachined ultrasonic transducers (pMUTs) for the frequency range of 2-10 MHz, optimized for maximum coupling coefficient, as a function of device design. With the help of original tools designed for the purpose, a comprehensive build-test finite element model was developed to predict and measure the device performance.

Superantigens produced by Streptococcus pyogenes have been implicated with streptococcal toxic shock syndrome (STSS). We analyzed 19 acute-phase serum samples for mitogenic activity from patients with severe streptococcal disease. The [...]

Exactly how the staphylococcal enterotoxins function as superantigens by attaching to the T-cell antigen receptors (TCR) and the major histocompatibility complex class II molecules has become clearer due to experiments using hybrid molecules. These experiments showed that amino-acid residues at the carboxyl terminus allow the enterotoxins to focus on different TCR beta-chain binding sites. The enterotoxins' crystalline morphology also aids in reacting to TCR.

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 superantigenic properties of Staphylococcal enterotoxin-like X (SElX) have recently been established. We now reveal that SElX also possesses functional characteristics of the SSLs. A region of SElX displays high homology to the sialyl-lactosamine (sLacNac)-specific binding site present in a sub-family of SSLs. By analysing the interaction of SElX with sLacNac-containing glycans we show that SElX has an equivalent specificity and host cell binding range to the SSLs. Mutation of key amino acids in this conserved region affects the ability of SElX to bind to cells of myeloid origin and significantly reduces its ability to protect S. aureus from destruction in a whole blood killing (WBK) assay. Like the SSLs, SElX is up-regulated early during infection and is under the control of the S. aureus exotoxin expression (Sae) two component gene regulatory system. Additionally, the structure of SElX in complex with the sLacNac-containing tetrasaccharide sialyl Lewis X (sLeX) reveals that SElX is a unique single-domain SAg. In summary, SElX is an ‘SSL-like’ SAg. [ABSTRACT FROM AUTHOR]

Group AStreptococcus(GAS) infections are a significant global cause of morbidity and mortality. GAS diseases disproportionally affect those living in conditions characterized by poverty and social injustice, in both developing countries and in marginalized populations of industrialized nations. In Australia and New Zealand, GAS-associated Acute Rheumatic Fever (ARF) is a major cause of health inequality disproportionally affecting indigenous children. Recognition of these inequalities by the governments of Australia and New Zealand has resulted in the formation of a Trans-TasmanCoalition toAdvanceNewVaccines for groupAStreptococcus (CANVAS). This review provides an update on the current status of GAS vaccine development, and describes global efforts by CANVAS and others to accelerate the development of GAS vaccines. [ABSTRACT FROM PUBLISHER]

Summary Objectives To analyse the incidence, demographics and molecular epidemiology of invasive group A streptococcal (GAS) disease in New Zealand between 2002 and 2012. Methods Using laboratory-based surveillance data, invasive GAS isolates were identified from the Institute of Environmental Science and Research, New Zealand. Hospitalization and mortality data were obtained from the New Zealand Ministry of Health. Molecular typing was performed by sequence analysis of the emm gene. Results The incidence of invasive GAS infections increased from 3.9 per 100,000 population in 2002 to 7.9 per 100,000 population ( P < 0.001) in 2012. The incidence was highest in the over 75-year age group, and in Pacific peoples. There was temporal variation in emm types associated with invasive GAS disease, with emm 1 being the overall predominant emm type. The diversity of emm types varied significantly according to ethnicity. Overall, 59% of GAS isolates were theoretically covered by an experimental M-protein vaccine. Conclusions Our study provides valuable data on the epidemiology of invasive GAS disease in New Zealand, and represents one of the few studies to assess such longitudinal data across an entire nation. The increase in invasive GAS disease is concerning, and reasons for this should be explored further. [ABSTRACT FROM AUTHOR]

Virus like particles (VLPs) are potent immunogens capable of priming strong protective antibody responses due to their repetitive structural arrangement and affinity for specific B cell receptors. By contrast, T cell responses to VLPs can be weak due to inefficient uptake and processing by antigen presenting cells. We report here a novel strategy for increasing the T cell reactivity of a VLP, the nucleocapsid of hepatitis B virus, through covalent coupling of M1, an engineered form of the Streptococcal superantigen SMEZ2, that binds MHC II with high affinity but lacks its T cell mitogenic capability. M1:HBcAg conjugates bound to dendritic cells and were efficiently endocytosed into late endosomes. Human dendritic cells pulsed with M1:HBcAgs stimulated HBV-specific CD8+ T cells more effectively than cells pulsed with native capsids indicating that the modified VLP was more effectively cross presented by APCs. Coupling of M1 was also able to induce significantly greater reactivity of human CD4+ T cells specific for a common T-helper epitope. These studies indicate the potential of recombinant superantigens to act as flexible molecular adjuvants that can be incorporated into various subunit vaccine platforms leading to enhanced T cell reactivity in humans. [ABSTRACT FROM AUTHOR]

The synthesis of (±)-7-deoxythysanone and three analogues has been developed. The key oxa-Pictet-Spengler reaction enabled the synthesis of the naphthopyran precursor, which could be readily converted to 7-deoxythysanone and three related analogues. The biological activity of these compounds was also evaluated against HRV 3C protease, the results of which suggest that inhibition of the enzyme requires the presence of the 7-oxa functionality. [ABSTRACT FROM AUTHOR]

Background New Zealand has a higher incidence of Staphylococcus aureus disease than other developed countries, with significant sociodemographic variation in incidence rates. In contrast to North America, the majority of disease is due to methicillin-susceptible S. aureus (MSSA), although relatively little is known about the comparative demographics of MSSA and methicillin-resistant S. aureus (MRSA) infections in New Zealand. Methods Our objectives were to describe the trends, incidence and patient demographics of all S. aureus infections in patients presenting to our institution between 2001 and 2011, and compare the epidemiology of MSSA and MRSA infections. We identified all patients with S. aureus infections over the study period. A unique S. aureus infection was defined as the first positive S. aureus culture taken from the same patient within a thirty-day period. Standard definitions were used to classify episodes into community- or healthcare-associated S. aureus infection. Results There were 16,249 S. aureus infections over the study period. The incidence increased significantly over the study period from 360 to 412 per 100,000 population (P < 0.001), largely driven by an increase in community-associated non-invasive MSSA infections. When compared with MSSA infections, patients with non-multiresistant MRSA infections were more likely to be older, have hospital-onset infections and be Māori or Pacific Peoples. Conclusions Our work provides valuable baseline data on the epidemiology and trends of S. aureus infections in New Zealand. The significant increase in community-associated S. aureus infections is of public health importance. Future studies should investigate the reasons underlying this concerning trend. [ABSTRACT FROM AUTHOR]