Genetic plasticity promotes evolution and a vast diversity in Escherichia coli varying from avirulent to highly pathogenic strains, including the emergence of virulent hybrid microorganism. This ability also contributes to the emergence of antimicrobial resistance. These hybrid pathogenic E. coli (HyPEC) are emergent threats, such as O104:H4 from the European outbreak in 2011, aggregative adherent bacteria with the potent Shiga-toxin. Here, we briefly revisited the details of these E. coli classic and hybrid pathogens, the increase in antimicrobial resistance in the context of a genetically empowered multifaceted and versatile bug and the growing need to advance alternative therapies to fight these infections.
The mucosal chemokine CCL28 is highly upregulated during infection but its role in this context is not well understood. Utilizing Ccl28-/- mice, we discovered that CCL28 promotes neutrophil recruitment to the infected mucosa. Neutrophils from these tissues expressed the CCL28 receptor CCR3, and CCR3 stimulation enhanced neutrophil antimicrobial activity against Salmonella. Moreover, bone marrow neutrophils harbored pre-formed intracellular CCR3 that was rapidly mobilized to the cell surface following phagocytosis or inflammatory stimuli. The functional consequences of CCL28 deficiency were strikingly different between two infection models, as Ccl28-/- mice were highly susceptible to Salmonella gut infection, but highly resistant to otherwise lethal Acinetobacter lung infection. CCL28 thus plays a critical role in the immune response to mucosal pathogens by regulating neutrophil recruitment and activation, a response whose ultimate consequence ranges from beneficial (control of the pathogen) to exceedingly negative (death of the host), depending on the infectious agent and impacted organs.
Enterohemorrhagic (EHEC) and enteropathogenic Escherichia coli (EPEC) are human intestinal pathogens of clinical importance and their mechanism of pathogenicity is widely studied. However, both EHEC and EPEC poorly infect mice, whereas they do not develop important characteristics of the disease, hindering studies about mechanisms of virulence in vivo. Citrobacter rodentium exhibits high similarity of its genes with these human pathogens, including the island of pathogenicity Locus of Enterocyte Effacement (LEE). Therefore, C. rodentium becomes an alternative in vivo model for microorganisms that harbor LEE. The QseC directly regulates LEE as well as virulence mechanisms on these pathogens. Here, we report a novel surface motility in C. rodentium QseC-mediated in this non-flagellated bacterium. Moreover, we show norepinephrine and ethanolamine act as environmental signals in this movement. Hence, this study clarifies a novel role of the sensor QseC in completely unreported motility process of C. rodentium.
Bone substitutes based on hydroxyapatite (HA) and Bonefill ® (BO-inorganic bovine bone) associated with poly(lactic-co-glycolic acid) (PLGA) (HA/PLGA and BO/PLGA) were evaluated concerning cytotoxicity, genotoxicity and mutagenicity as potential candidates for bone repair. The materials were developed and provided by Bionnovation Biomedical Products Ltda. Eluates from these bone substitutes were prepared for toxicity evaluations using eukaryotic cell cultures. HA/PLGA was used as a comparison for Bonefill ®. Cell viability was evaluated by XTT assay and surviving fraction was calculated for clonogenic survival. Additionally, tail moment was used to assess genotoxicity (comet assay). The frequencies of binucleated cells with micronucleus (FBMN), micronucleus (FMN), nucleoplasmic bridges (NPBs), and nuclear buds (NBUDs) were analysed by cytokinesis-block micronucleus assay (CBMN assay). Results showed no statistical difference in cell viability compared with negative control (NC) The eluates did not promote delayed cytotoxicity whereas the surviving fraction rate for cultured cells was similar to NC. Furthermore, no genotoxicity or mutagenicity effects were observed for cultured cells with the Bonefill/PLGA and HA/PLGA eluates. In conclusion, the negative cytotoxicity, genotoxicity and mutagenicity results indicate that these bone substitutes presented interesting preliminary results as potential biomaterials for bone repair.
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