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Pseudomonas aeruginosa is one of the main causative agents of nosocomial infections and the spread of multidrug-resistant strains is rising. Therefore, novel strategies for therapy are urgently required. The outer membrane composition of Gram-negative pathogens and especially of Pa restricts the efficacy of antibiotic entry into the cell and determines virulence. For efficient outer membrane protein biogenesis, the β-barrel assembly machinery (BAM) complex in the outer membrane and periplasmic chaperones like Skp and SurA are crucial. Previous studies indicated that the importance of individual proteins involved in outer membrane protein biogenesis may vary between different Gram-negative species. In addition, since multidrug-resistant Pa strains pose a serious global threat, the interference with both virulence and antibiotic resistance by disturbing outer membrane protein biogenesis might be a new strategy to cope with this challenge. Therefore, deletion mutants of the non-essential BAM complex components bamB and bamC, of the skp homolog hlpA as well as a conditional mutant of surA were investigated. The most profound effects for both traits were associated with reduced levels of SurA, characterized by increased membrane permeability, enhanced sensitivity to antibiotic treatment and attenuation of virulence in a Galleria mellonella infection model. Strikingly, the depletion of SurA in a multidrug-resistant clinical bloodstream isolate re-sensitized the strain to antibiotic treatment. From our data we conclude that SurA of Pa serves as a promising target for developing a drug that shows antiinfective activity and re-sensitizes multidrug-resistant strains to antibiotics.

Complement resistance is an important virulence trait of Yersinia enterocolitica (Ye). The predominant virulence factor expressed by Ye is Yersinia adhesin A (YadA), which enables bacterial attachment to host cells and extracellular matrix and additionally allows the acquisition of soluble serum factors. The serum glycoprotein vitronectin (Vn) acts as an inhibitory regulator of the terminal complement complex by inhibiting the lytic pore formation. Here, we show YadA-mediated direct interaction of Ye with Vn and investigated the role of this Vn binding during mouse infection in vivo. Using different Yersinia strains, we identified a short stretch in the YadA head domain of Ye O:9 E40, similar to the ‘uptake region' of Y. pseudotuberculosis YPIII YadA, as crucial for efficient Vn binding. Using recombinant fragments of Vn, we found the C-terminal part of Vn, including heparin-binding domain 3, to be responsible for binding to YadA. Moreover, we found that Vn bound to the bacterial surface is still functionally active and thus inhibits C5b-9 formation. In a mouse infection model, we demonstrate that Vn reduces complement-mediated killing of Ye O:9 E40 and, thus, improved bacterial survival. Taken together, these findings show that YadA-mediated Vn binding influences Ye pathogenesis. © 2017 Karger Publishers

Background: Education is important in improving economies and creating literate, self-reliant and healthy societies. However, hunger is a barrier to basic education in Malawi. Hunger is also associated with a number of health risk behaviours, such as bullying, suicide ideation and unhygienic behaviours that may jeopardize the future of children. There are, however, limited data on the prevalence and associated factors of hunger among school children in Malawi.Methods: The study used data from the Malawi Global School-Based Health Survey conducted in 2009 to estimate the prevalence of self-reported hunger within the last 30 days among primary and secondary school age group. It also assessed the association between self-reported hunger and some selected list of independent variables using frequency distribution, chisquared test and logistic regression.Results: A total of 2359 students were available for analysis. The overall selfreported prevalence of hunger within the last 30 days was 12.5% (18.9% (172) in the rural and 8.3% (115) in urban areas; and 11.9%(123) for male and 12.5(148) for female children). In the final analysis, geographical location, eating fruits, having been bullied, suicide ideation, and washing hands with soap were significantly associated with hunger.Conclusion: Hunger in both primary and secondary school children in Malawi is a major social problem. The design of school feeding programmes aimed to reduce hunger should incorporate the factors identified as associated with hunger.