The antigen 43 structure reveals a molecular velcro-like mechanism of autotransporter-mediated bacterial clumping

Aggregation and biofilm formation are critical mechanisms for bacterial resistance to host immune factors and antibiotics. Autotransporter (AT) proteins, which represent the largest group of outer-membrane and secreted proteins in Gram-negative bacteria, contribute significantly to these phenotypes. Despite their abundance and role in bacterial pathogenesis, most AT proteins have not been structurally characterized, and there is a paucity of detailed information with regard to their mode of action. Here we report the structure���function relationships of Antigen 43 (Ag43a), a prototypic self-associating AT protein from uropathogenic Escherichia coli. The functional domain of Ag43a displays a twisted L-shaped β-helical structure firmly stabilized by a 3D hydrogen-bonded scaffold. Notably, the distinctive Ag43a L shape facilitates self-association and cell aggregation. Combining all our data, we define a molecular “Velcro-like” mechanism of AT-mediated bacterial clumping, which can be tailored to fit different bacterial lifestyles such as the formation of biofilms.

Structure and function of DsbA, a key bacterial oxidative folding catalyst

Since its discovery in 1991, the bacterial periplasmic oxidative folding catalyst DsbA has been the focus of intense research. Early studies addressed why it is so oxidizing and how it is maintained in its less stable oxidized state. The crystal structure of Escherichia coli DsbA (EcDsbA) revealed that the oxidizing periplasmic enzyme is a distant evolutionary cousin of the reducing cytoplasmic enzyme thioredoxin. Recent significant developments have deepened our understanding of DsbA function, mechanism, and interactions: the structure of the partner membrane protein EcDsbB, including its complex with EcDsbA, proved a landmark in the field. Studies of DsbA machineries from bacteria other than E. coli K-12 have highlighted dramatic differences from the model organism, including a striking divergence in redox parameters and surface features. Several DsbA structures have provided the first clues to its interaction with substrates, and finally, evidence for a central role of DsbA in bacterial virulence has been demonstrated in a range of organisms. Here, we review current knowledge on DsbA, a bacterial periplasmic protein that introduces disulfide bonds into diverse substrate proteins and which may one day be the target of a new class of anti-virulence drugs to treat bacterial infection. Antioxid. Redox Signal. 14, 1729–1760.

Intersectionality, rural criminology, and re-imaging the boundaries of critical criminology

One of the significant shortcomings of the criminological canon, including its critical strands – feminist, cultural and green – has been its urbancentric bias. In this theoretical model, rural communities are idealised as conforming to the typical small-scale traditional societies based on cohesive organic forms of solidarity and close density acquaintance networks. This article challenges the myth that rural communities are relatively crime free places of ‘moral virtue’ with no need for a closer scrutiny of rural context, rural places, and rural peoples about crime and other social problems. This challenge is likewise woven into the conceptual and empirical narratives of the other articles in this Special Edition, which we argue constitute an important body of innovative work, not just for reinvigorating debates in rural criminology, but also critical criminology. For without a critical perspective of place, the realities of context are too easily overlooked. A new criminology of crime and place will help keep both critical criminology and rural criminology firmly anchored in the sociological and the criminological imagination. We argue that intersectionality, a framework that resists privileging any particular social structural category of analysis, but is cognisant of the power effects of colonialism, class, race and gender, can provide the theoretical scaffolding to further develop such a project.

Disturbed microtubule function and induction of micronuclei by chelate complexes of mercury(II)

Interactions of mercury(II) with the microtubule network of cells may lead to genotoxicity. Complexation of mercury(II) with EDTA is currently being discussed for its employment in detoxification processes of polluted sites. This prompted us to re-evaluate the effects of such complexing agents on certain aspects of mercury toxicity, by examining the influences of mercury(II) complexes on tubulin assembly and kinesin-driven motility of microtubules. The genotoxic effects were studied using the micronucleus assay in V79 Chinese hamster fibroblasts. Mercury(II) complexes with EDTA and related chelators interfered dose-dependently with tubulin assembly and microtubule motility in vitro. The no-effect-concentration for assembly inhibition was 1 μM of complexed Hg(II), and for inhibition of motility it was 0.05 μM, respectively. These findings are supported on the genotoxicity level by the results of the micronucleus assay, with micronuclei being induced dose-dependently starting at concentrations of about 0.05 μM of complexed Hg(II). Generally, the no-effect-concentrations for complexed mercury(II) found in the cell-free systems and in cellular assays (including the micronucleus test) were identical with or similar to results for mercury tested in the absence of chelators. This indicates that mercury(II) has a much higher affinity to sulfhydryls of cytoskeletal proteins than to this type of complexing agents. Therefore, the suitability of EDTA and related compounds for remediation of environmental mercury contamination or for other detoxification purposes involving mercury has to be questioned.

Behaviour v structure : Tribunal’s AGL Energy merger authorisation

Section 95AT of the Competition and Consumer Act 2010 (Cth) (CCA) provides that the Tribunal may grant an authorisation to acquire shares or assets that would otherwise contravene s 50. Section 95AT was inserted by the Trade Practices Legislation Amendment Act 2006 (Cth) and commenced on 1 January 2007. In Application for Authorisation of Macquarie Generation by AGL Energy Limited, (AGL Energy) the Tribunal has for the first time granted AGL Energy Limited (AGL) a conditional authorisation to acquire the assets of Macquarie Generation from the NSW Government.