Successful establishment of infection by bacterial pathogens requires fine-tuning of virulence-related genes. Quorum sensing (QS) is a global regulation process based on the synthesis of, detection of, and response to small diffusible molecules, called N-acyl-homoserine lactones (AHL), in gram-negative bacteria. In numerous species, QS has been shown to regulate genes involved in the establishment of pathogenic interactions with the host. Brucella melitensis produces N-dodecanoyl homoserine lactones (C 12 -HSL), which down regulate the expression of flagellar genes and of the virB operon (encoding a type IV secretion system), both of which encode surface virulence factors. A QS-related regulator, called VjbR, was identified as a transcriptional activator of these genes. We hypothesized that VjbR mediates the C 12 -HSL effects described above. vjbR alleles mutated in the region coding for the AHL binding domain were constructed to test this hypothesis. These alleles expressed in trans in a ⌬vjbR background behave as constitutive regulators both in vitro and in a cellular model of infection. Interestingly, the resulting B. melitensis strains, unable to respond to AHLs, aggregate spontaneously in liquid culture. Preliminary characterization of these strains showed altered expression of some outer membrane proteins and overproduction of a matrix-forming exopolysaccharide, suggesting for the first time that B. melitensis could form biofilms. Together, these results indicate that QS through VjbR is a major regulatory system of important cell surface structures of Brucella and as such plays a key role in host-pathogen interactions.Brucella spp. are gram-negative intracellular pathogens belonging to the ␣-2 proteobacteria group, like Agrobacterium, Rhizobium, and Rickettsia, which also live in close association with a eukaryotic host (46). Bacteria of the genus Brucella are the etiologic agents of brucellosis, a worldwide zoonosis affecting a broad range of mammals and triggering important economic losses (63). Three Brucella species, B. melitensis, B. abortus, and B. suis, are able to infect humans, causing a chronic, debilitating disease with severe, sometimes fatal outcomes.Brucellae are remarkably well adapted to the intracellular lifestyle, being able to invade and to survive within macrophages and nonprofessional phagocytes (17,51). This is one of the bases for the still poorly understood chronicity of brucellosis (26). This aptitude relies on the perturbation of vesicular trafficking and the creation of a unique intracellular replication niche derived from the endoplasmic reticulum (7,8).Brucella is confronted with very diverse environments and host defenses both in the extracellular milieu and inside host cells. It is thus expected that this pathogen has to sense external and internal signals to achieve successful adaptation throughout its infectious cycle. Among such systems, quorum sensing (QS), stringent response, and signal transduction through two-component regulators have been particularly well studied (fo...
Mutations in the Brucella melitensis quorum-sensing (QS) system are involved in the formation of clumps containing an exopolysaccharide. Here, we show that the overexpression of a gene called aiiD in B. melitensis gives rise to a similar clumping phenotype. The AiiD enzyme degrades AHL molecules and leads therefore to a QS-deficient strain. We demonstrated the presence of exopolysaccharide and DNA, two classical components of extracellular matrices, in clumps produced by this strain. We also observed that the production of outer membrane vesicles is strongly increased in the aiiD-overexpressing strain. Moreover, this strain allowed us to purify the exopolysaccharide and to obtain its composition and the first structural information on the complex exopolysaccharide produced by B. melitensis 16M, which was found to have a molecular weight of about 16 kDa and to be composed of glucosamine, glucose and mostly mannose. In addition, we found the presence of 2-and/or 6-substituted mannosyl residues, which provide the first insights into the linkages involved in this polymer. We used a classical biofilm attachment assay and an HeLa cell infection model to demonstrate that the clumping strain is more adherent to polystyrene plates and to HeLa cell surfaces than the wild-type one. Taken together, these data reinforce the evidence that B. melitensis could form biofilms in its lifecycle.
The Status Quo Bias (SQB) describes an individual's preference to avoid changes and maintain the current situation. In today’s world, technological advances require nearly constant change within organizations. Thus, SQB can become an issue when it hinders progress. Therefore, it is crucial to understand how this effect can be reliably measured and, even more importantly, what countermeasures to employ. Prior research has focused more on individual measuring approaches and less on countermeasures. As researchers across different research fields have studied this bias, we conduct a literature review spanning different scholarly fields. This broader research focus allows us to identify four measurement approaches and 13 countermeasures along the three aspects of cognitive misperception, rational decision making, and psychological commitment of SQB. Our overview consolidates existing knowledge and will hopefully be the starting point for researchers to start combating this bias where needed. Successful and proven countermeasures can, for example, increase the acceptance and adoption of digital innovations and technology in general and thereby allow organizations to capitalize on their investments.
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