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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]

A study concerning the role of argenase in Helicobacter pylori physiology is presented. Results include the cloning of H. pylori gene.

Background: Manuka honey is recognized for it's health-promoting properties and it's use in medicine is well documented. However, the actions of Manuka honey are limited by rapid digestion and the inactivation of bioactive components such as methylglyoxal. Cyclodextrins are naturally occurring glucose rings that improve stability and bioactivity of products. This study investigates the tolerability and bioactivity of α-cyclodextrin-complexed Manuka honey called Manuka Honey with CycloPower ™. Methods: The antibacterial properties of Manuka honey complexed with α-cyclodextrin (Manuka honey with Cyclopower™) were compared to uncomplexed Manuka honey against a range of common organisms using standard measurements of minimum inhibitory (MIC) and bactericidal (MBC) concentrations. Time course growth measurements were determined using a sublethal concentration of 2% w (honey solids)/v and measuring the area under the growth curve. Results: In tube MIC assays, Manuka honey completely inhibited Staphylococcus aureus (MSSA and MRSA), Streptococcus pyogenes, Helicobacter pylori and Moraxella catarrhalis at concentrations of 10% w/v or less, with MIC values decreasing as the methylglyoxal content of the honeys increased from 100 to 550 mg/kg. MIC values at a given methlyglyoxal level were also decreased for S. pyogenes, M. catarrhalis and H. pylori by complexing the Manuka honey with α-cyclodextrin. Pseudomonas aeruginosa was not inhibited by any of the Manuka honey or Cyclopower treatments at the concentrations tested (2-10% w/v). Manuka honey with CyclopowerTM had an increased bacteriostatic action against S. aureus, MRSA and P. aeruginosa compared with Manuka honey. Conclusions: This study concludes that Manuka honey is an effective antibacterial agent that can be enhanced by complexing with α-cyclodextrin. [ABSTRACT FROM AUTHOR]

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. aureus lineages are largely host-specific. The use of such animal-adapted S. aureus strains may therefore be a promising approach for developing more clinically relevant animal infection models. We have isolated a mouse-adapted S. aureus strain (JSNZ) which caused a severe outbreak of preputial gland abscesses among male C57BL/6J mice. We aimed to extensively characterize this strain on a genomic level and determine its virulence potential in murine colonization and infection models. JSNZ belongs to the MLST type ST88, rare among human isolates, and lacks an hlb-converting phage encoding human-specific immune evasion factors. Naive mice were found to be more susceptible to nasal and gastrointestinal colonization with JSNZ than with the human-derived Newman strain. Furthermore, naïve mice required antibiotic pre-treatment to become colonized with Newman. In contrast, JSNZ was able to colonize mice in the absence of antibiotic treatment suggesting that this strain can compete with the natural flora for space and nutrients. In a renal abscess model, JSNZ caused more severe disease than Newman with greater weight loss and bacterial burden. In contrast to most other clinical isolates, JSNZ can also be readily genetically modified by phage transduction and electroporation. In conclusion, the mouse-adapted strain JSNZ may represent a valuable tool for studying aspects of mucosal colonization and for screening novel vaccines and therapies directed at preventing colonization. [ABSTRACT FROM AUTHOR]

Summary Depletion of dendritic cells from UV-B-irradiated sheep skin was investigated by monitoring migration of these cells towards regional lymph nodes. By creating and cannulating pseudoafferent lymphatic vessels draining a defined region of skin, migrating cells were collected and enumerated throughout the response to UV-B irradiation. In the present study, the effects of exposing sheep flank skin to UV-B radiation clearly demonstrated a dose-dependent increase in the migration of Langerhans cells (LC) from the UV-B-exposed area to the draining lymph node. The range of UV-B doses assessed in this study included 2.7 kJ/m2, a suberythemal dose; 8 kJ/m2, 1 minimal erythemal dose (MED); 20.1 kJ/m2; 40.2 kJ/m2; and 80.4 kJ/m2, 10 MED. The LC were the cells most sensitive to UV-B treatment, with exposure to 8 kJ/m2 or greater reproducibly causing a significant increase in migration. Migration of γδ+ dendritic cells (γδ+ DC) from irradiated skin was also triggered by exposure to UV-B radiation, but dose dependency was not evident within the range of UV-B doses examined. This, in conjunction with the lack of any consistent correlation between either the timing or magnitude of migration peaks of these two cell types, suggests that different mechanisms govern the egress of LC and γδ+ DC from the skin. It is concluded that the depression of normal immune function in the skin after exposure to erythemal doses of UV-B radiation is associated with changes in the migration patterns of epidermal dendritic cells to local lymph nodes. [ABSTRACT FROM AUTHOR]

Despite recent advances in our understanding of how Helicobacter pylori causes disease, the factors that allow this pathogen to persist in the stomach have not yet been fully characterized. To identify new virulence factors in H. pylori, we generated low-infectivity variants of a mouse-colonizing H. pylori strain using the classical technique of in vitro attenuation. The resulting variants and their highly infectious progenitor bacteria were then analyzed by global gene expression profiling. The gene expression levels of five open reading frames (ORFs) were significantly reduced in low-infectivity variants, with the most significant changes observed for ORFs HP1583 and HP1582. These ORFs were annotated as encoding homologs of the Escherichia coli vitamin B(6) biosynthesis enzymes PdxA and PdxJ. Functional complementation studies with E. coli confirmed H. pylori PdxA and PdxJ to be bona fide homologs of vitamin B(6) biosynthesis enzymes. Importantly, H. pylori PdxA was required for optimal growth in vitro and was shown to be essential for chronic colonization in mice. In addition to having a well-known metabolic role, vitamin B(6) is necessary for the synthesis of glycosylated flagella and for flagellum-based motility in H. pylori. Thus, for the first time, we identify vitamin B(6) biosynthesis enzymes as novel virulence factors in bacteria. Interestingly, pdxA and pdxJ orthologs are present in a number of human pathogens, but not in mammalian cells. We therefore propose that PdxA/J enzymes may represent ideal candidates for therapeutic targets against bacterial pathogens.