Measuring Behavior Change Resulting from EORE and the Need for Complementary Risk Reduction Activities

Risk education (RE) in mine action has been around since 1992.[i] However, explosive ordnance risk education (EORE)[ii] operators are still struggling to measure how and whether EORE has resulted in positive behavior change.[iii] Of course, various monitoring and evaluation (M&E) methods have been pursued in the past, predominantly the use of knowledge, attitude, practice, and beliefs (KAPB) surveys; simpler pre-/post-EORE session surveys; the use of proxy indicators such as number of explosive ordnance (EO) accidents or victims; and number of explosive ordnance disposal (EOD) callouts from the community. However, these methods come with some limitations in accurately capturing behavior change. For example, survey questions linked to behavior would normally be prefaced as “what would you do if…” However, this self-reporting of behavior does not necessarily capture actual behaviors; moreover, responses may be biased toward giving the “correct answer” in order to please the organization conducting the survey. Further, research has evaluated the limits of EORE in the context of ongoing conflict, high levels of poverty, and/or insufficient clearance/ordnance disposal capacity. These circumstances lead to a lack of choices for persons living in or near an EO-contaminated environment to adopt safer behavior

Salmonella bongori provides insights into the evolution of the Salmonellae.

The genus Salmonella contains two species, S. bongori and S. enterica. Compared to the well-studied S. enterica there is a marked lack of information regarding the genetic makeup and diversity of S. bongori. S. bongori has been found predominantly associated with cold-blooded animals, but it can infect humans. To define the phylogeny of this species, and compare it to S. enterica, we have sequenced 28 isolates representing most of the known diversity of S. bongori. This cross-species analysis allowed us to confidently differentiate ancestral functions from those acquired following speciation, which include both metabolic and virulence-associated capacities. We show that, although S. bongori inherited a basic set of Salmonella common virulence functions, it has subsequently elaborated on this in a different direction to S. enterica. It is an established feature of S. enterica evolution that the acquisition of the type III secretion systems (T3SS-1 and T3SS-2) has been followed by the sequential acquisition of genes encoding secreted targets, termed effectors proteins. We show that this is also true of S. bongori, which has acquired an array of novel effector proteins (sboA-L). All but two of these effectors have no significant S. enterica homologues and instead are highly similar to those found in enteropathogenic Escherichia coli (EPEC). Remarkably, SboH is found to be a chimeric effector protein, encoded by a fusion of the T3SS-1 effector gene sopA and a gene highly similar to the EPEC effector nleH from enteropathogenic E. coli. We demonstrate that representatives of these new effectors are translocated and that SboH, similarly to NleH, blocks intrinsic apoptotic pathways while being targeted to the mitochondria by the SopA part of the fusion. This work suggests that S. bongori has inherited the ancestral Salmonella virulence gene set, but has adapted by incorporating virulence determinants that resemble those employed by EPEC.We thank the core sequencing and informatics teams at the Sanger Institute for their assistance and The Wellcome Trust for its support of the Sanger Institute Pathogen Genomics and Biology groups and the MRC for their support of GF, KSR and GNS. MCF, GCL, TRC, HSS, GSV, MS, NKP, RAK, JP, GD and NRT were supported by Wellcome Trust grant 076964 and MICROME, an EU Framework Programme 7 Collaborative Project, Grant Agreement Number 222886-2. Work was also supported by Grant ADI-08/2006 from Comisión Nacional de Investigación Científica y Tecnológica (CONICYT) and The World Bank, and grant 1100092 from Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT). CJB was supported by fellowships from CONICYT (21080373 and AT-24091015)

Anti-virulence Strategies to Target Bacterial Infections.

Resistance of important bacterial pathogens to common antimicrobial therapies and the emergence of multidrug-resistant bacteria are increasing at an alarming rate and constitute one of our greatest challenges in the combat of bacterial infection and accompanied diseases. The current shortage of effective drugs, lack of successful prevention measures and only a few new antibiotics in the clinical pipeline demand the development of novel treatment options and alternative antimicrobial therapies. Our increasing understanding of bacterial virulence strategies and the induced molecular pathways of the infectious disease provides novel opportunities to target and interfere with crucial pathogenicity factors or virulence-associated traits of the bacteria while bypassing the evolutionary pressure on the bacterium to develop resistance. In the past decade, numerous new bacterial targets for anti-virulence therapies have been identified, and structure-based tailoring of intervention strategies and screening assays for small-molecule inhibitors of such pathways were successfully established. In this chapter, we will take a closer look at the bacterial virulence-related factors and processes that present promising targets for anti-virulence therapies, recently discovered inhibitory substances and their promises and discuss the challenges, and problems that have to be faced