The nature of halogen bonding is examined via experimental and computational characterizations of a series of associates between electrophilic bromocarbons R-Br (R-Br=CBr3F, CBr3NO2, CBr3COCBr3, CBr3CONH2, CBr3CN, etc.) and bromide anions. The [R-Br, Br(-)] complexes show intense absorption bands in the 200-350 nm range which follow the same Mulliken correlation as those observed for the charge-transfer associates of bromide anions with common organic π-acceptors. For a wide range of the associates, intermolecular R-Br···Br(-) separations decrease and intramolecular C-Br bond lengths increase proportionally to the Br(-)→R-Br charge transfer; and the energies of R-Br···Br(-) bonds are correlated with the linear combination of orbital (charge-transfer) and electrostatic interactions. On the whole, spectral, structural and thermodynamic characteristics of the [R-Br, Br(-)] complexes indicate that besides electrostatics, the orbital (charge-transfer) interactions play a vital role in the R-Br···Br(-) halogen bonding. This indicates that in addition to controlling the geometries of supramolecular assemblies, halogen bonding leads to electronic coupling between interacting species, and thus affects reactivity of halogenated molecules, as well as conducting and magnetic properties of their solid-state materials.

The cyclic AMP receptor protein (Crp) is a transcriptional regulator that controls the expression of numerous bacterial genes, usually in response to environmental conditions and particularly by sensing the availability of carbon. In the plague pathogen Yersinia pestis, Crp regulates the expression of multiple virulence factors, including components of the type III secretion system and the plasminogen activator protease Pla. The regulation of Crp itself, however, is distinctly different from that found in the well-studied Escherichia coli system. Here, we show that at physiological temperatures, the synthesis of Crp in Y. pestis is positively regulated at the posttranscriptional level. The loss of the small RNA chaperone Hfq results in decreased Crp protein levels but not in steady-state Crp transcript levels, and this regulatory effect occurs within the 5′ untranslated region (UTR) of the Crp mRNA. The posttranscriptional activation of Crp synthesis is required for the expression of pla, and decoupling crp from Hfq through the use of an exogenously controlled promoter and 5′ UTR increases Pla protein levels as well as partially rescues the growth defect associated with the loss of Hfq. Finally, we show that both Hfq and the posttranscriptional regulation of Crp contribute to the virulence of Y. pestis during pneumonic plague. The Hfq-dependent, posttranscriptional regulation of Crp may be specific to Yersinia species, and thus our data help explain the dramatic growth and virulence defects associated with the loss of Hfq in Y. pestis.

No abstract

Bacterial pathogens have evolved extensive signaling pathways to translate environmental signals into changes in gene expression. While Crp has long been appreciated for its role in regulating metabolism of carbon sources in many bacterial species, transcriptional profiling has revealed that this protein regulates many other aspects of bacterial physiology. The plague pathogen Y. pestis requires this global regulator to survive in blood, skin, and lungs. During disease progression, this organism adapts to changes within these niches. In addition to regulating genes for metabolism of nonglucose sugars, we found that Crp regulates genes for virulence, metal acquisition, and quorum sensing by direct or indirect mechanisms. Thus, this single transcriptional regulator, which responds to changes in available carbon sources, can regulate multiple critical behaviors for causing disease.

Bacterial pathogenesis depends on changes in metabolic and virulence gene expression in response to changes within a pathogen's environment. The plague-causing pathogen, , requires expression of the gene encoding the Pla protease for progression of pneumonic plague. The catabolite repressor protein Crp, a global transcriptional regulator, may serve as the activator of in response to changes within the lungs as disease progresses. By using gene reporter fusions, the spatial and temporal activation of the and promoters was measured in a mouse model of pneumonic plague. In the lungs, was highly expressed in bacteria found within large aggregates resembling biofilms, while expression increased over time independent of the aggregated state. Increased expression of and correlated with a reduction in lung glucose levels. Deletion of the glucose-specific phosphotransferase system EIIBC (PtsG) of rescued glucose levels in the lungs, resulting in reduced expression of both and We propose that activation of expression during pneumonic plague is driven by an increase of both Crp and cAMP levels following consumption of available glucose in the lungs by Thus, Crp operates as a sensor linking the nutritional environment of the host to regulation of virulence gene expression. Using as a model for pneumonia, we discovered that glucose is rapidly consumed, leading to a catabolite-repressive environment in the lungs. As a result, expression of the gene encoding the plasminogen activator protease, a target of the catabolite repressor protein required for pathogenesis, is activated. Interestingly, expression of the catabolite repressor protein itself was also increased in the absence of glucose but only in biofilms. The data presented here demonstrate how a bacterial pathogen senses changes within its environment to coordinate metabolism and virulence gene expression.