Staphylococcus aureus causes the majority of skin and soft tissue infections. Half of patients treated for primary skin infections suffer recurrences within 6 months despite appropriate antibiotic sensitivities and infection control measures. We investigated whether S. aureus internalized by human skin keratinocytes are effectively eradicated by standard anti-staphylococcal antibiotics. S. aureus, but not S. epidermidis, were internalized and survive within keratinocytes without inducing cytotoxicity or releasing the IL-33 danger signal. Except for rifampicin, anti-staphylococcal antibiotics in regular clinical use, including flucloxacillin, teicoplanin, clindamycin, and linezolid, did not kill internalized S. aureus, even at 20-fold their standard minimal inhibitory concentration. We conclude that internalization of S. aureus by human skin keratinocytes allows the bacteria to evade killing by most anti-staphylococcal antibiotics. Antimicrobial strategies, including antibiotic combinations better able to penetrate into mammalian cells are required if intracellular S. aureus are to be effectively eradicated and recurrent infections prevented.

Background: S. aureus is the dominant infective trigger of atopic dermatitis (AD). How this bacterium drives type 2 allergic pathology in the absence of infection in AD patients is unclear.Objective: To identify the S. aureus-derived virulence factor(s) that initiates the cutaneous type 2-promoting immune response responsible for AD.Methods: In vitro human keratinocyte cell culture, ex vivo human skin organ explants and the eczema prone Nc/Tnd mouse were used as model systems to assess type-2 promoting immune responses to S. aureus. Identification of the bioactive factor was accomplished using Fast Protein Liquid Chromatography and mass spectrometry. Bioactivity was confirmed by cloning and expression in an E. coli vector system, and S. aureus Sbi mutant strains confirming loss of activity.Results: S. aureus was unique amongst staphylococcal species in its ability to induce the rapid release of constitutive IL-33 from human keratinocytes independent of the toll-like receptor pathway. Using the eczema-prone NC/Tnd mouse model, we showed that IL-33 was essential in inducing the immune response to S. aureus in vivo. By fractionation and candidate testing, we identified the Second Immunoglobulin-Binding Protein (Sbi) as the predominant staphylococcus-derived virulence factor that directly drives IL-33 release from human keratinocytes. Immunohistology of skin demonstrated that corneodesmosin, a component of corneodesmosomes that form key intercellular adhesive structures in the stratum corneum, was disrupted resulting in reduction of skin barrier function.Conclusion: S. aureus-derived Sbi is a unique type 2-promoting virulence factor capable of initiating the type-2 promoting cytokine activity underlying AD.

Every market intelligence on energy these days converges on a unanimous view that despite the push on developing alternative energies, fossil fuel will continue to play a pivotal role in world energy supply. The competition between fossil fuel and alternative energies is a new reality. To maintain a competitive edge, sustainability and favorable economic returns shape the UAE's approach to future oil developments. UAE oil production is analyzed to reflect the critical importance of production contribution to the world and within the MENA region. Two published international field development cases are analyzed, focusing on the impact of aggressive approach on production sustainability, potential challenges and costs in developing the remaining bypassed oil. By using typical Abu Dhabi reservoir field data, various development scenarios are simulated demonstrating potential impact on production sustainability, ultimate recovery and economical value for the country. Today National Oil Companies (NOC's) have an advantage as they own and control more than 90% of the total world oil and gas reserves. In contrast, the top six largest International Oil Companies (IOC's) combined control less than 5% of the total. Clearly, IOC's will face challenges in reserves replacement. Although there are different factors affecting reserves replacement rate, one of the key to enhanced economic reserves position for IOC's is field depletion strategy. An ideal field depletion strategy would see production at lower depletion rates to ensure efficient reservoir drainage for maximizing recovery. An aggressive field depletion strategy can potentially generate faster monetary returns through higher production, but may create by- passed oil that would be difficult and costly to extract. An optimal field depletion strategy ensures sustainable development, maximizes ultimate recovery, and generates highest value return for the country and all stakeholders. A careful approach is required while deciding between these two different approaches, as the decision can have long lasting implications on corporates economic reserve position and global energy supply landscape. For example, a small improvement in ultimate recovery of existing reservoirs worldwide would add to and sustain affordable supplies, but a small reduction can potentially lead to supply shortages hindering world economic growth. This paper presents the untold story of Abu Dhabi's Recovery Based Strategy. The aim is to perform a detailed analysis and comparison between two different development approaches, namely Aggressive Approach aiming to generate quick monetary value through high production (high depletion rates), and optimal / moderate field depletion strategy prioritizing sustainable development, and high ultimate recovery for all stakeholders.